Mus Micro hauv Leptospirosis raum Kab Mob

Abstract:Leptospirosis yog ib hom kab mob zoonotic thiab dej yug thoob ntiaj teb. Nws yog ib tug tsis saib tsis xyuaskis kab mobtshwm sim los ntawmLeptospiraspp., nrog rau cov kab mob rov tshwm sim thiab teeb meem kev noj qab haus huv thoob ntiaj teb txog kev mob nkeeg thiab kev tuag ntawm tib neeg thiab tsiaj txhu. Leptospirosis tshwm sim ua tus thawj cojua rau mob febrilenroghepatorenal raug mobhauv ntau lub tebchaws, suav nrog Thaib teb. Txawm hais tias feem ntau cov neeg cuam tshuam yog cov tsos mob ntawm tus kab mob hnyav, uas ib txwm nyuaj rau kev sib txawv ntawm lwm cov kab mob tropical, muaj cov pov thawj loj hlob ntawm cov tsos mob me me uas ua rau cov tsos mob tsis paub txog. Lub raum yog ib qho ntawm cov kabmob uas cuam tshuam los ntawm Leptospires. Txawm hais tias mob raum raug mob nyob rau hauv lub spectrum ntawm interstitial nephritis yog ib tug zoo-paub yam ntxwv ntawm mob leptospirosis,mob raum moblos ntawm leptospirosis yog dav tham. Thaum ntxov paub txog mob leptospirosis ua rautxo morbidity thiab tuag. Yog li, hauv qhov kev tshuaj xyuas no, peb qhia txog qhovspectrum ntawm cov yam ntxwvkoom nrogleptospirosis mob raumthiab kev siv serologic thiabtxoj kev molecular, nrog rau kev kho mob hnyav leptospirosis.

Ntsiab lus:mob raum raug mob;tiv thaiv kab mob; interstitial nephritis; leptospirosis

YUAV UA LI CAS RAU CISTANCHE ua haujlwm rau cov neeg mob rau lub raum?

1. Taw qhia

Leptospirosis yog ib yam kab mob zoonotic nyob rau hauv cheeb tsam kub thiab subtropical. Kev kis tus kab mob leptospirosis feem ntau tshwm sim hauv thaj chaw muaj kabmob kis thaum lub caij los nag thiab dej nyab. Leptospirosis tseem yog ib qho teeb meem loj hauv ntiaj teb kev noj qab haus huv nrog kev nce zuj zus vim lub ntiaj teb sov sov thiab kev hloov pauv huab cua. Kev ua ub no sab nraum zoov, xws li rafting, canoeing, triathlons, los yog da dej nyob rau hauv tej yam ntuj tso lub cev ntawm cov dej, tau raug tshaj tawm tias muaj feem cuam tshuam rau tus kab mob leptospirosis [1,2], thaum muaj kev pheej hmoo ua hauj lwm cuam tshuam nrog qee cov hauj lwm, suav nrog kev ua liaj ua teb, tshuaj kho tsiaj, tub rog, kev tshawb fawb ua haujlwm, thiab nyob ze ntawm tsob ntoo roj hmab [2,3]. Tus kab mob kis tau tus kab mob leptospirosis feem ntau tshwm sim los ntawm kev sib cuag ncaj qha (tshwj xeeb tshaj yog nrog cov tawv nqaij tsis zoo ntawm tus tswv tsev) nrog cov kab mob sib kis (cov zis) los ntawm cov kab mob los yog cov tsiaj muaj kab mob nrog rau cov kab mob ib puag ncig, xws li dej thiab av, qhov chaw kab mob Leptospira. tuaj yeem nyob tau ob peb lub lis piam [2]. Ntau cov tsiaj qus tau raug tshaj tawm tias yog cov chaw cia khoom, tab sis cov nas xim av (Rattus norvegicus) yog lub pas dej loj tshaj plaws uas tau tshaj tawm hauv ntau thaj chaw thoob ntiaj teb [4]. Txawm hais tias muaj qhov tsis sib haum xeeb ntawm cov kab mob leptospirosis, kev sib cuam tshuam ntawm lub cev tiv thaiv kab mob thiab cov kab mob spirochete (Leptospira strain) tau lees paub tias yog qhov tseem ceeb rau kev nthuav qhia tus kab mob nyob rau theem mob lossis mob ntev.

Lub raum yog lub hom phiaj tseem ceeb ntawm Leptospira nyob rau hauv ob qho tib si mob thiab ntev ntawm tus kab mob. Cov kev kho mob ntawm tus mob leptospirosis hnyav yog biphasic yam ntxwv [1–4]. Ua ntej, leptospires nkag mus rau tus tswv tsev mucocutaneous teeb meem uas ua rau lub cev tiv thaiv kab mob uas ua rau muaj ntau yam tshuaj tiv thaiv kab mob thiab tso zis. Tom qab ntawd, nyob rau theem tiv thaiv kab mob, leptospires raug tshem tawm los ntawm cov kab mob hauv lub cev tab sis tsis yog raum [2]. Yog li, kev faib cov leptospires hauv lub raum thaum lub sijhawm mob hnyav tuaj yeem cuam tshuam rau kev ua haujlwm ntawm lub raum tsis zoo thaum lub sijhawm ntev. Mob raum raug mob (AKI) tom qab leptospirosis yog tus cwj pwm los ntawm mob tubulointerstitial nephritis los ntawm kev tiv thaiv kab mob tiv thaiv kab mob microbial los yog lwm yam (xws li hyperbilirubinemiamia lossis rhabdomyolysis-induced myoglobinuria), nrog rau lub raum tubular microinstruction. Kev nthuav qhia subacute thiab ntev ntawm leptospires nyob rau hauv lub raum proximal tubules nyob rau hauv ib lub xeev muaj peev xwm mus rau mob tubulointerstitial nephritis (CTIN) thiab fibrosis [5]. Yog li ntawd, kev tswj hwm lub cev tiv thaiv kab mob rau cov kab mob tuaj yeem tiv thaiv kab mob raum ntev (CKD) thiab ntau lub cev puas tsuaj los ntawm leptospirosis. Vim li no, asymptomatic leptospirosis raum kab mob yuav tsum raug txiav txim siab rau qhov kev kuaj mob sib txawv ntawm lub raum fibrosis thiab CKD ntawm qhov tsis paub, tshwj xeeb tshaj yog rau cov neeg mob uas nyob hauv thaj chaw muaj kab mob.

Lub raum yog lub hom phiaj tseem ceeb ntawm Leptospira nyob rau hauv ob qho tib si mob thiab ntev ntawm tus kab mob. Cov kev kho mob ntawm tus mob leptospirosis hnyav yog biphasic yam ntxwv [1–4]. Ua ntej, leptospires nkag mus rau tus tswv tsev mucocutaneous teeb meem uas ua rau lub cev tiv thaiv kab mob uas ua rau muaj ntau yam tshuaj tiv thaiv kab mob thiab tso zis. Tom qab ntawd, nyob rau theem tiv thaiv kab mob, leptospires raug tshem tawm los ntawm cov kab mob hauv lub cev tab sis tsis yog raum [2]. Yog li, kev faib cov leptospires hauv lub raum thaum lub sijhawm mob hnyav tuaj yeem cuam tshuam rau kev ua haujlwm ntawm lub raum tsis zoo thaum lub sijhawm ntev. Mob raum raug mob (AKI) tom qab leptospirosis yog tus cwj pwm los ntawm mob tubulointerstitial nephritis los ntawm kev tiv thaiv kab mob tiv thaiv kab mob microbial los yog lwm yam (xws li hyperbilirubinemiamia lossis rhabdomyolysis-induced myoglobinuria), nrog rau lub raum tubular microobstruction. Kev nthuav qhia subacute thiab ntev ntawm leptospires nyob rau hauv lub raum proximal tubules nyob rau hauv ib lub xeev muaj peev xwm mus rau mob tubulointerstitial nephritis (CTIN) thiab fibrosis [5]. Yog li ntawd, kev tswj hwm lub cev tiv thaiv kab mob rau cov kab mob tuaj yeem tiv thaiv kab mob raum tsis zoo (CKD) thiab ntau lub cev puas tsuaj los ntawm leptospirosis. Vim li no, asymptomatic leptospirosis raum kab mob yuav tsum raug txiav txim siab rau qhov kev kuaj mob sib txawv ntawm lub raum fibrosis thiab CKD ntawm qhov tsis paub, tshwj xeeb tshaj yog rau cov neeg mob uas nyob hauv thaj chaw muaj kab mob.

Kev kuaj mob ntawm leptospirosis kuj yog ib kauj ruam tseem ceeb rau kev ua tau zoo dua. Txawm hais tias muaj ntau qhov kev kuaj mob sai thiab txhim kho rau cov kab mob leptospirosis tam sim no muaj [6], cov txiaj ntsig tsis zoo yuav tsum tsis txhob suav tias tsis suav nrog leptospirosis, tshwj xeeb tshaj yog nyob rau hauv cov xwm txheej uas muaj kev tsis txaus ntseeg. Kev kho empirical yuav tsum tau pib ua ke nrog kev ua xyem xyav ntawm kev kuaj mob leptospirosis vim tias kev tswj hwm tshuaj tiv thaiv kab mob thaum ntxov tuaj yeem tiv thaiv cov neeg mob los ntawm kev loj hlob mus rau ntau hom kab mob.

2. Kab mob sib kis

Although the actual incidence of leptospirosis worldwide is not precisely known, the age and gender-adjusted disease morbidity models estimated annually 1.03 million cases and 58,900 deaths worldwide [7], where the highest estimated disease morbidity and mortality were observed in South and Southeast Asia, Oceania, Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa [7]. In Thailand, the incidence of leptospirosis is reported at around 6.6 per 100,000 population, with a 1.5% fatality rate. The northeastern region has the highest incidence (12.5 per 100,000 population), depending on the season, and the highest incidence occurs during the rainy season from August to October each year [8]. According to a recent study by Torgerson et al. [9], a total of 2.90 million Disability Adjusted Life Years, estimated >70% ntawm tus kab mob cholera thoob ntiaj teb raws li kev kwv yees ntawm 2010 Daim ntawv tshaj tawm thoob ntiaj teb tus kab mob (GBD) [10]. Yog li ntawd, leptospirosis zoo li yog tus kab mob loj tshaj plaws uas cuam tshuam txog kev noj qab haus huv [7]. Tsis tas li ntawd, nrog cov dej nyab ntau zuj zus vim lub ntiaj teb sov sov hauv ob lub teb chaws tsim thiab tsim, leptospirosis tsis txwv rau cov teb chaws sov. Lwm qhov teeb meem ntawm qhov teeb meem yog qhov teeb meem semantic lossis epistemological vim tias ntau dua 50% ntawm cov neeg mob leptospirosis uas muaj lossis tsis muaj lub raum cuam tshuam yog asymptomatic lossis pom cov tsos mob me [11]. Yog li, nws yog ib qho tseem ceeb uas yuav tau xav txog tus nqi ntawm leptospirosis nyob rau hauv cov neeg mob uas muaj kab mob nrog AKI kev koom tes los yog cov neeg uas muaj CKD ntawm etiology tsis paub meej, vim leptospirosis tuaj yeem ua rau cov kab mob tsis paub txog. Cov teeb meem ntawm leptospirosis tuaj yeem suav nrog ntau lub cev puas tsuaj hauv 5-10% ntawm tag nrho cov kis mob [12]. Ntxiv mus, leptospirosis ua rau AKI, ntawm cov nqi sib txawv ntawm 10-88% nyob ntawm qhov txhais ntawm AKI [13,14]. Cov Kab Mob Raum Txhim Kho Ntiaj Teb Cov Txheej Txheem (KDIGO) cov txheej txheem kev kho mob rau AKI hauv xyoo 2012 txhais AKI raws li kev hloov pauv ntawm cov ntshav creatinine (SCr) ntau dua 0.3 mg / dL hauv 48 h lossis nce hauv SCr mus rau 1.5 npaug ntawm tus nqi pib hauv yav dhau los ib lub lim tiam nrog rau cov zis tso zis tsawg (Daim duab 1). Hauv Teles et al.'s [14] kev tshawb nrhiav rov qab ntawm 205 tus neeg mob leptospirosis nrog AKI, 55.1% ntawm cov neeg mob AKI raug cais raws li KDIGO 3, thaum 16.1% tau muab cais ua KDIGO 1 thiab 17.6% raws li KDIGO 2. Txawm li cas los xij, qhov pom Cov ntaub ntawv zoo li qhia tau tias muaj ntau yam ntawm AKI raws li tau hais los ntawm KDIGO cov txheej txheem txawm hais tias qhov kev qhia me me ntawm leptospirosis. Qhov no tuaj yeem yog vim qhov tsis txaus ntseeg ntawm KDIGO cov qauv, lossis qhov xwm txheej siab ntawm AKI hauv leptospirosis tsis hais txog qib ntawm qhov hnyav. Kev lees paub tseeb ntawm qhov tseeb ntawm AKI hauv leptospirosis nrog ntau lub ntsiab lus yog xav tau. Cov kev pheej hmoo ntawm leptospirosis sib txawv raws li lub teb chaws thiab cheeb tsam ntawm kev kawm thiab tuaj yeem raug cais raws li kev ua haujlwm, kev coj tus cwj pwm, thiab ib puag ncig kev pheej hmoo. Kamath et al. [15] tau ua ib txoj kev tshawb fawb txog pej xeem raws li kev tswj hwm nyob rau yav qab teb Is Nrias teb uas muaj kev ua haujlwm, xws li kev ua si sab nraum zoov (qhov sib txawv ntawm qhov sib txawv [OR] ntawm 3.95) lossis muaj kev txiav los yog qhov txhab ntawm lub cev thaum ua haujlwm (OR: 4.88) , thiab tej yam ib puag ncig, xws li kev sib cuag nrog cov nas los ntawm cov zaub mov paug (LOSSIS: 4.29) lossis kev sib cuag nrog cov av lossis dej paug cov zis (OR: 4.58), tau pom tias muaj feem cuam tshuam nrog leptospirosis. Lub caij no, kev tshawb fawb rov qab los ntawm Thaib teb tau qhia tias nyob ze cov ntoo cog ntoo nrog rau kev da dej hauv lub cev ntawm cov dej ob lub lis piam ua ntej tus kab mob tau cuam tshuam nrog kev pheej hmoo ntawm mob leptospirosis loj dua piv rau cov kab mob leptospirosis uas tsis mob hnyav (OR: 12. {45}} thiab 7.25, ntsig txog). Tshwj xeeb tshaj yog, cov neeg mob feem ntau raug nthuav tawm thaum da dej hauv dej tsis tu ncua (41.9%), maj mam ntws dej (29.0%), thiab av nkos (29.0%) [2]. Tsis tas li ntawd, cov neeg mob leptospirosis tau nce ntxiv ntawm kev kis kab mob mus ncig. Qhov kwv yees kwv yees qhov tshwm sim txhua xyoo ntawm cov kab mob leptospirosis cuam tshuam txog kev mus ncig hauv cheeb tsam Asia sab hnub tuaj yog kwv yees li 1.78 rau 100,000 cov neeg taug kev hauv ib xyoos piv nrog qhov xwm txheej ntawm qhov xwm txheej ntawm 0.06 rau 100,000 cov pej xeem hauv ib xyoos (kev pheej hmoo ratio [RR] 29.6), uas feem ntau muaj feem xyuam rau cov dej num ntsig txog dej [16].

Cov txheej txheem ntawm proximal tubular defects tshwm sim los ntawm Leptospira spp. (A) Cov duab ntawm lub cev ib txwm muaj thiab cov channel tseem ceeb koom nrog hauv kev tswj hwm ntawm intraluminal bicarbonate, phosphate, sulfate, qabzib, thiab amino acids ntawm aquaporin (AQP)-1 channel, sodium– hydrogen exchanger (NHE) 3 ( los yog sodium-hydrogen antiporter 3), thiab sodium / phosphate cotransporter (Na / Pi). (B) Leptospira ua rau raug mob raws cov tubules ze ze, ua rau muaj kev hloov pauv ntawm cov luminal gate channels hauv ob qho tib si apical thiab basolateral membranes, piv txwv li, txo qis hauv NHE3, AQP1 channels, thiab txo qis ntawm -Na+ /K{{7} }ATPase raws apical thiab basolateral membranes, raws li. Li no, nyob rau hauv lub luminal ib feem, muaj ib tug tsub zuj zuj ntawm dej dawb (ua rau polyuria), sodium nkos, thiab cov yam ntxwv ntawm Fanconi lub tubular tsis ua hauj lwm, nrog rau bicarbonaturia, hyperphosphaturia, thiab qabzib.

3. Pathophysiology

3.1. Mob raum mob hauv Leptospirosis

AKI yog ib qho kev tshwm sim ntawm leptospirosis. Lub raum kev koom tes hauv leptospirosis txawv ntawm asymptomatic urinary abnormalities mus rau hnyav AKI uas yuav tsum tau kev pab dialysis. Feem ntau lub raum pathology nyob rau hauv leptospirosis yog mob tubulointerstitial nephritis (ATIN), hos hypokalemia thiab sodium nkos yog ib qho kev kuaj pom. Interestingly, AKI tshwm sim los ntawm leptospirosis feem ntau tsis yog-oliguric, thiab hypokalemia suav txog 45-50% ntawm tag nrho cov mob AKI [17]. ATIN los ntawm leptospirosis yog tus cwj pwm los ntawm diffuse interstitial edema thiab mononuclear cell infiltration. Tshwj xeeb, glomerular kev koom tes hauv leptospirosis tsis tshua muaj. Leptospirosis-induced vasculitis yog qhov tsawg, nrog rau lub raum tsis zoo uas tuaj yeem txo qis los ntawm kev tswj hwm corticosteroid [18-21]. Cov txheej txheem sib txawv tau thov rau cov uas tsis yog-oliguric, hypokalemic AKI hauv leptospirosis (saib hauv qab).

Tubular Dysfunction thiab Lwm Electrolyte Disturbances

Ob peb qhov tsis xws luag hauv tubular kuj tau tshaj tawm, xws li bicarbonaturia, glucosuria txo qis cov tubule sodium reabsorption, thiab siab excretion ntawm phosphate thiab uric acid, tseem hu ua Fanconi syndrome [11,22,23]. Kev txo qis hauv sodium-hydrogen ex-changer isoform 3 (NHE3), uas tau nthuav tawm nrog rau aquaporin 1 (AQP1) hauv apical daim nyias nyias ntawm cov tubule ze ze, thiab qhov txo qis hauv -Na + / K + -ATPase [24] ua rau muaj ntau yam teeb meem. Hyponatremia hauv leptospirosis yog vim muaj ntau yam ua rau, suav nrog nce zis sodium poob, cellular efflux ntawm sodium los ntawm Na + / K + -ATPase tsis xws luag, nce qib ntawm antidiuretic hormone (ADH), thiab rov pib dua osmoreceptors [25]. Yog li, kev sib xyaw ua ke ntawm cov ntaub ntawv kho mob ntawm hyponatremia, hypokalemia, thiab non-oliguric AKI (los yog polyuria) yog cov yam ntxwv tshwj xeeb ntawm leptospirosis nephropathy.

Tsis tas li ntawd, kev txo qis ntawm sodium-potassium-2-chloride co-transporter (NKCC2) hauv medullary tuab ascending limb (mTAL) ntawm lub voj ntawm Henle kuj tseem tuaj yeem piav qhia txog kev poob ntawm sodium thiab potassium hauv cov zis [24, 26,27] (Daim duab 2). Polyuria lossis non-oliguric AKI tshwm sim thaum thawj theem ntawm leptospirosis tuaj yeem yog lwm cov tsos mob ntsig txog kev txo qis ntawm aquaporin 2 (AQP2) thiab tso zis tsis haum vim tsis kam ntawm sab hauv medullary sau duct rau vasopressin. Thaum lub sij hawm rov qab los ntawm AKI, AQP2 qhia tau nce raws li cov txheej txheem them nyiaj [24].

Hypomagnesemia kuj muaj nyob rau hauv cov neeg mob leptospirosis nrog AKI los ntawm magnesium nkos [28]. Ib txoj kev tshawb nrhiav kev sim kuj tau tshaj tawm lub raum magnesium nkos theem nrab kom txo qis NKCC2 ntawm lub apical membrane ntawm mTAL [27] (Daim duab 2). Yog li, hypomagnesemia thiab hypophosphatemia tshwm sim los ntawm hypermagnesuria thiab hyperphosphaturia, raws li, yuav tsum tau saib xyuas kom zoo thaum muaj kab mob leptospirosis. Hypomagnesemia los ntawm tubular dysfunction nyob rau hauv leptospirosis tuaj yeem ua rau muaj kev hloov pauv hauv magnesium homeostasis, uas xav tau ntau ntawm magnesium hloov, tshwj xeeb tshaj yog rau cov neeg mob myalgia, lethargy, thiab arrhythmias. Ntawm qhov tod tes, kev kho sai ntawm hypomagnesemia tuaj yeem ua rau nce qib magnesium ntau ntxiv vim leptospirosis tuaj yeem ua rau AKI, uas tuaj yeem txo qis magnesium clearance. Ib yam li ntawd, hnyav hypophosphatemia (txhais tau tias yog ntshav phosphate<1.5 mg/dL) from proximal tubulopathy may contribute to metabolic encephalopathy and myopathy. Accordingly, as per the authors' experience, serum magnesium and phosphate levels should be evaluated every 3–5 days and 1–2 days, respectively, particularly in severe leptospirosis.

Interestingly, leptospirosis-hais txog AKI qee zaus yuav tsum muaj kev txhawb nqa raum hloov kho nyob rau theem mob hnyav. Lub raum tuaj yeem rov zoo tag nrho tom qab ua tiav cov kev kho mob antimicrobial thaum ntxov. Kev kho mob zoo ntawm leptospirosis rov ua dua tubular tsis ua haujlwm hauv kev tshawb fawb hauv vitro [27]. Cov neeg mob Leptospirosis kuj muaj txiaj ntsig zoo dua nrog cov tsis yog oliguric dua li nrog oliguric AKI [17].

Daim duab 2. Daim duab qhia txog cov kab mob ntawm cov kab mob hypokalemia, hypomagnesemia, thiab hypocalcemia hauv cov kab mob leptospirosis raum. (A) Sodium-potassium-2 chloride cotransporter (lub raum tshwj xeeb cation Cl- coupled cotransporter, NKCC2) yog ib qho tseem ceeb cotransporter uas tswj cov homeostasis ntawm intraluminal cations thiab anions. (B) NKCC2 ua haujlwm nrog cov poov tshuaj raws (ROMK) thiab Paracelliar xaiv cov protein raws ntawm magnesium (lub ntsiab) thiab calcium (me), hu ua claudin 16 thiab 19, kom tswj tau intraluminal zoo hluav taws xob. (C) Zoo ib yam li pharmacological inhibition ntawm NKCC2 los ntawm furosemide, poob ntawm NKCC2 tswj vim tubular raug mob los ntawm Leptospira, ua rau poob ntawm intraluminal zoo hluav taws xob nqi, uas ua rau txo reabsorption ntawm magnesium thiab calcium. Yog li, cov qib qis ntawm magnesium (hypomagnesemia) thiab calcium (hypocalcemia) nyob rau hauv kev, tig, muab cov lus pom zoo (ntsuab xub ntsuab) thiab txhim kho cov poov tshuaj tso rau hauv lub lumen kom tswj hwm homeostasis. Lub Ca / Mg receptor nyob rau ntawm lub basolateral membrane kom deb li deb hu ua calcium sensing receptor (CaSR), uas yog tus tseem ceeb molecular player koom nrog sodium, potassium, thiab chloride thauj los ntawm tuab ascending limb. Thaum lub sij hawm hypocalcemia thiab / lossis hypomagnesemia, inactivation ntawm basolateral CasSR txhim kho ROMK. Thaum kawg, ntau cov poov tshuaj yuav poob rau hauv cov zis

3.2. Leptospirosis nrog Systemic Inflammatory Response Syndrome (SIRS)

Mob leptospirosis mob hnyav yog nyuaj los ntawm sepsis thiab septic shock [29,30]. Nyob rau theem pib, leptospirosis muaj feem cuam tshuam nrog kev ua kom muaj zog ntawm cov kab mob inflammasomes thiab proinflammatory cytokines, ua rau lub raum mob thiab kev puas tsuaj tom qab. Leptospira tuaj yeem pom nyob rau hauv cov kab mob sib luag ntawm hnub 10 ntawm tus kab mob, thiab tom qab ntawd nws tuaj yeem pom hauv tubular lumen hnub 14 ntawm tus kab mob [31]. Nws cov antigens kuj pom muaj nyob rau hauv proximal tubular cells, macrophages, thiab interstitium [32].

Cov txheej txheej membrane proteins (OMPs) ntawm Leptospira muaj cov tshuaj tiv thaiv kab mob thiab cov kab mob sib kis, suav nrog lipoproteins, lipopolysaccharides (LPS), thiab peptidoglycans, uas txiav txim siab cov tswv teb cov lus teb. Hauv cov qauv tsiaj ntawm sepsis, LPS lossis endotoxin ua rau muaj kev puas tsuaj rau tus tswv tsev [33,34]. Leptospira LPS, nyob rau ntawm OMP, zoo li yog cov tshuaj tiv thaiv loj uas cuam tshuam rau kev tiv thaiv kab mob Leptospira, thiab ntseeg tias nws cov dej num muaj feem cuam tshuam rau kev sib cuam tshuam ntawm tus tswv tsev-cov kab mob uas txiav txim siab virulence thiab pathogenesis. Txhawm rau elucidate cov txheej txheem ntawm tubule-interstitial raug mob los ntawm Leptospira, Leptospiral OMPs tau muab rho tawm los ntawm kab lis kev cai nas raum epithelial hlwb, uas tau qhia txog ntau yam ntawm cov noob ntsig txog tubular cell raug mob thiab mob [35]. Cov Leptospiral OMPs qhib cov khoom siv hluav taws xob hloov hluav taws xob kappa B (NF-KB), activator protein-1, thiab ntau cov noob caj noob ces tau qhia hauv cov medullary tuab ascending limb hlwb [35]. LipL32, ib tug loj pathogenic lipoprotein ntawm OMP, induces tubulointerstitial nephritis-mediated gene qhia nyob rau hauv nas proximal tubular hlwb thiab yog ib tug tseem ceeb immunogen thaum lub sij hawm tus kab mob leptospirosis nyob rau hauv tib neeg [36]. Tsis tas li ntawd, LipL32 yog ib qho hemolysin uas ua rau hemolysis ntawm erythrocytes thaum lub sij hawm Leptospira kab mob [37], thiab nws ncaj qha cuam tshuam rau proximal tubular cells los ntawm kev nce cov noob thiab cov protein ntau ntawm ntau cov pro-inflammatory cytokines, suav nrog inducible nitric oxide (iNOS), monocyte. chemoattractant protein-1 (MCP-1), thiab qog necrosis factor- (TNF- ). Yog li, kev txheeb xyuas cov OMPs tshiab ntawm Leptospira yuav tsum nyob twj ywm qhov tseem ceeb rau kev paub txog leptospirosis pathogenesis thiab kev kho mob.

Hu xov tooj zoo li receptors (TLRs) yog cov proteins uas paub txog cov qauv molecular ntawm cov kab mob thiab sawv cev rau thawj kab ntawm kev tiv thaiv kab mob hauv lub cev tiv thaiv kab mob. Cov teebmeem ntawm TLRs tau raug soj ntsuam los txiav txim siab seb TLRs tuaj yeem kho qhov kev mob tshwm sim los ntawm Leptospiral OMP hauv lub raum proximal tubular cells. Qhov zoo siab, tsuas yog TLR2 tab sis tsis yog TLR4 nce qhov kev qhia ntawm iNOS thiab MCP-1. Raws li, qhov kev tshawb pom qhia tias kev txhawb nqa ntawm iNOS thiab MCP-1 tshwm sim los ntawm cov kab mob Leptospiral OMPs, tshwj xeeb tshaj yog LipL32, nyob rau hauv cov kab mob sib luag yuav tsum tau TLR2 (feem ntau yog co-expressed nrog TLR1) rau cov lus teb thaum ntxov [5].

Tom qab ntawd, ib qho cascade ntawm o yog qhib rau hauv lub raum tubular hlwb, raws li leptospirosis induces interleukin (IL) -1 thiab IL-18 secretion los ntawm tib neeg macrophage hlwb los ntawm reactive oxygen hom thiab cathepsin B mediated-NLRP3 inflammasome activation. [38]. Lwm cov cytokines thiab chemokines, suav nrog IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), thiab TNF- [39], kuj raug tsim thaum lub sij hawm leptospirosis kab mob. Mob cytokine thiab chemokine surges tshwm sim nyob rau hauv cov neeg mob leptospirosis tuaj yeem ua rau muaj kev cuam tshuam ntawm sepsis thiab mob hnyav sepsis vim qhov tsis sib xws ntawm cov lus teb pro- thiab cov tshuaj tiv thaiv. Nce qib ntawm MCP-1, IL-11, thiab me me inducible cytokine A2 tshwm sim thaum leptospirosis nrog thrombocytopenia [40]. Cov kev tshawb pom no qhia txog lub luag haujlwm ntawm cytokine thiab chemokine ntau lawm thaum lub sij hawm mob thiab subacute theem ntawm tus kab mob leptospirosis. Hloov pauv, kev ua kom mob ntsws ntev ntev yuav yog txoj hauv kev uas ua rau lub raum parenchyma fibrosis lossis CKD [41].

AKI tom qab leptospirosis tej zaum yuav tshwm sim vim mob tubular necrosis (ATN) los ntawm ischemia thiab lub raum tsis zoo perfusion raws li qhov tshwm sim ntawm sepsis thiab septic shock. Tsis tas li ntawd, sepsis-associated AKI (sepsis-AKI) hauv leptospirosis kuj tseem ua tau, tshwj xeeb tshaj yog rau cov neeg mob uas muaj ntshav siab. Cov ntaub ntawv pov thawj los ntawm ob qho tib si kev sim thiab kev soj ntsuam kev tshawb fawb qhia tau hais tias septic shock tshwm sim rau hauv sepsis-txog kev tiv thaiv kab mob hauv lub xeev, ua rau tuag ntawm tus tswv tsev vim yog kev tiv thaiv kab mob hauv lub cev thiab kev tiv thaiv kab mob [42]. Yog li ntawd, circulating cytokines thiab chemokines tuaj yeem cuam tshuam nrog kev tiv thaiv kab mob hauv cov kab mob leptospirosis hnyav; Piv txwv li, cov qib neutrophil qis qis tuaj yeem cuam tshuam nrog kev ua haujlwm tsis zoo ntawm cov tshuaj tiv thaiv kab mob [43–45].

3.3. Kab mob raum ntev hauv Leptospirosis

Qhov tshwm sim ntawm ATIN tshwm sim los ntawm tus kab mob leptospirosis muaj xws li tubular atrophy thiab interstitial nephritis nyob rau hauv qhov kev tshwm sim ntawm kev kho mob tsis ua tiav lossis rov ua tsis tiav. Nyob rau hauv ib qho kev sim los piav qhia txog kev sib koom ua ke ntawm Leptospira thiab lub raum fibrosis, cov teebmeem ntawm OMP los ntawm cov kab mob Leptospira ntawm kev tsim khoom thiab sib sau ua ke ntawm extracellular matrix tau tshawb pom [46]. Kev khi ntawm Leptospiral OMP rau cov kab mob sib luag, HK-2 hlwb, ua rau muaj kev nce qib ntawm hom I thiab hom IV collagens nyob rau hauv koob tshuaj. Ib yam li ntawd, lub zog hloov pauv kev loj hlob zoo (TGF)- 1 tso tawm tau nce ob zaug tom qab qhov sib ntxiv ntawm Leptospira OMP, thaum anti-TGF- 1-neutralizing antibodies attenuated nce ntau lawm ntawm hom I thiab hom IV collagen, qhia. kev koom tes ntawm TGF- 1 hauv cascade. Qhov tshwm sim no tau lees paub los ntawm kev hloov pauv nuclear ntau ntxiv ntawm SMAD3 tom qab kev tswj hwm ntawm Leptospiral OMP, thiab overexpression ntawm qhov tseem ceeb-tsis zoo SMAD3 tiv thaiv Leptospiral OMP-induced nce ntawm hom I thiab IV collagen ntau lawm yam tsis muaj kev cuam tshuam rau metalloproteinase kev ua [46]. Qhov no qhia tau hais tias cov teebmeem ntawm Leptospiral OMP nyob rau hauv cov nqe lus ntawm kev txhim kho extracellular matrix synthesis kho los ntawm TGF- 1/SMAD txoj kev.

Txawm hais tias cov ntaub ntawv los ntawm ob qho tib si hauv vitro thiab hauv vivo kev tshawb fawb qhia tau tias muaj peev xwm ntawm CKD thiab lub raum fibrosis vim tus kab mob leptospirosis [46-48], cov txiaj ntsig tau los ntawm ob qho tib si meta-analysis [49] thiab lub sijhawm ntev, peb xyoos tom qab- Kev tshawb nrhiav tsis sib haum, vim tsis muaj cov neeg mob lepleptospirosis nrog kev lim ntshav dependence tau tshaj tawm [50]. Tubulointerstitial nephritis (CTIN) yog ib qho mob uas tshwm sim nrog rau cov kab mob leptospirosis ntev uas yuav ua rau CKD ntawm qhov tsis paub txog etiology thiab tom qab lub raum tsis ua haujlwm. Sustained tubulointerstitial lymphocyte infiltration tej zaum yuav yog ib qho tseem ceeb uas ua rau kev loj hlob mus rau CKD [50]. Tej zaum, TLRs tuaj yeem koom nrog hauv AKI-CKD txuas ntxiv hauv leptospirosis vim TLRs paub tias yog qhov tseem ceeb hauv cov lus teb tseem ceeb rau ob qho tib si hauv lub cev thiab kev tiv thaiv kab mob [47] nrog rau ischemia-reperfusion raug mob, glomerulonephritis, thiab sepsis-AKI. . Yog li ntawd, cov kev tshawb fawb ntxiv yuav tsum nrhiav kev txheeb xyuas cov yam ntxwv ntawm cov molecular uas yuav ua rau muaj teeb meem txaus ntshai los ntawm kev ua rau cov lus teb rau qhov sib txawv ntawm exogenous thiab endogenous noxious stimuli.