Kev sib raug zoo ntawm Cerebral Ischemia-Reperfusion Injury Thiab Cell Apoptosis

Lub hlwb yog ib qho tseem ceeb tshaj plaws ntawm tib neeg lub cev. Nyob rau hauv xyoo tas los no, nrog kev nce ntxiv hauv cov xwm txheej ntawm cov kab mob plawv thiab cerebrovascular, cov kab mob no ua ke nrog cov kab mob plawv thiab cov qog nqaij hlav ua rau peb cov kab mob loj heev. Cerebral ischemia yog lub ntsiab ua rau cov kab mob plawv thiab cerebrovascular, uas tuaj yeem ua rau cov ntaub so ntswg hauv lub hlwb thiab nws txoj haujlwm, thiab qhov kev puas tsuaj yog cuam tshuam nrog lub sijhawm ntev ntawm ischemia thiab cov ntshav seem.

Nyem rau cistanche tubulosa Australia rau Ischemia Reperfusion raug mob

Tom qab cerebral ischemia restores cov ntshav nyob rau hauv ib lub sij hawm, lub hlwb ua hauj lwm tsis rov qab, thiab ntau loj neurological puas ntawm lub hlwb ua hauj lwm tshwm sim. Qhov tshwm sim no hu ua cerebral ischemia-reperfusion raug mob[1][2]. Cov txheej txheem pathogenic ntawm cerebral ischemia-reperfusion raug mob feem ntau cuam tshuam nrog ntau yam teebmeem xws li excitatory amino acid toxicity, ntau dawb radical tsim, thiab inflammatory teb, thiab tom qab cerebral ischemia, ntau cov neurons nyob ib ncig ntawm qhov chaw raug mob reperfusion yuav tshwm sim Apoptotic tuag. , uas yog, cerebral ischemia-reperfusion raug mob yog ze ze rau apoptosis. Daim ntawv no piav qhia txog kev tshawb fawb tam sim no.

Kev sib raug zoo ntawm Cerebral Ischemia-Reperfusion Injury thiab Neuronal Apoptosis

Cov kev tshawb fawb tau pom tias muaj ob hom kev tuag ntawm tes los ntawm cerebral ischemia-reperfusion raug mob: necrosis thiab apoptosis. Lub sijhawm ntawm ischemic raug mob thiab qhov kev ncua deb ntawm cov paj hlwb thiab lub chaw ischemic koom ua ke txiav txim siab txog kev tuag ntawm tes: thaum lub sijhawm ischemia ntev dua, uas yog, thaum lub hlwb tsis txaus nrog oxygen rau lub sijhawm ntev vim yog ischemia hnyav. thiab nyob hauv qhov chaw ischemic, ib qho kev poob qis hauv cov ntshav feem ntau ua rau cov cell necrosis; Lub sijhawm luv luv ntawm ischemia tsuas yog ua rau me me mus rau nruab nrab hypoxic-ischemia, thiab cov paj hlwb nyob hauv lub penumbra ntawm thaj chaw ischemic central, uas yog, cov paj hlwb nyob ib ncig ntawm thaj chaw ischemic central, feem ntau yog apoptotic.

Thaum lub cell tuag [3], lub ntim ntawm lub cell shrinks, thiab kev sib txuas nrog cov nyob ib ncig ntawm lub hlwb ploj, yog li nws yuav raug cais tawm ntawm cov cell nyob ib puag ncig, lub cytoplasm ceev ntawm lub cell yuav nce, lub peev xwm ntawm mitochondrial membrane yuav. ploj mus, thiab tom qab ntawd cov permeability yuav hloov, tso cytochrome C mus txog cytoplasm, cov nucleoplasm yog condensed, cov ntaub so ntswg nuclear thiab nucleolus tawg, DNA yog degraded mus rau hauv fragments, thiab thaum kawg tsim apoptotic lub cev, uas yog phagocytized los ntawm cov hlwb nyob ib sab los yog phagocytes. [4].

Txoj hauv kev ntawm neuronal cell apoptosis tshwm sim los ntawm cerebral ischemia-reperfusion raug mob

2.1 Endogenous mitochondria-mediated apoptosis txoj kev

Thaum cov paj hlwb raug txhawb los ntawm ischemia, txoj hauv kev mitochondrial apoptotic hauv cov paj hlwb tuaj yeem qhib tau, ua rau depolarization ntawm mitochondrial membrane thiab txo qis ntawm daim nyias nyias, nce permeability ntawm cov mitochondrial membrane sab nrauv thiab tso tawm cytochrome C. los ntawm mitochondria.

Tom qab cytochrome C raug tso tawm rau hauv lub cell, nws cuam tshuam nrog Apaf-1 los ua ib qho apoptotic complex nrog kev pab ntawm ATP thiab dATP. Lub apoptotic complex recruits thiab activates Pro-Caspase 9 los tsim ib tug Caspase 9 holoenzyme, thiab lub Caspase 9 holoenzyme ntxiv Activate the effector Caspase3 thiab Caspase7, pib cov caspase cascade cov tshuaj tiv thaiv, thiab txiav ntau tshaj 100 hom substrates hauv hlwb, xws li - tubulin, Actin, PARPA, Lamin, thiab lwm yam, yog li ua rau paj hlwb apoptosis [5].

2.2 Endogenous endoplasmic reticulum-mediated apoptosis txoj kev

Lub endoplasmic reticulum yog qhov chaw ua haujlwm tseem ceeb rau kev tsim cov protein thiab lub tsev khaws khoom ntawm Ca2 ntxiv. Cerebral ischemia-reperfusion raug mob tuaj yeem ua rau muaj kev cuam tshuam ntawm intracellular Ca2 ntxiv rau qib, yog li ua rau muaj kev ntxhov siab ntawm endoplasmic reticulum. Endoplasmic reticulum kev ntxhov siab tuaj yeem txo cov protein synthesis hauv hlwb, nce protein ntau folding, thiab tswj Ca2 ntxiv rau homeostasis, tab sis kev ntxhov siab ntau dhau tuaj yeem cuam tshuam Ca2 ntxiv rau homeostasis hauv endoplasmic reticulum thiab ntau ntawm Ca2 ntxiv yuav nkag mus rau hauv lub cell sab hauv thiab sab hauv mitochondria, ntawm ib sab, nws yuav cuam tshuam rau kev ua haujlwm ntawm mitochondria thiab Bcl-2 tsev neeg cov proteins, ua rau cov hlwb mus rau apoptosis, thiab ntawm qhov tod tes, qhib cov intracellular neutral cysteine ​​endopeptidase Calpain. Lub tshuab txais Calpain tuaj yeem ua rau Caspase Cascade cov tshuaj tiv thaiv uas cuam tshuam rau apoptosis [6][7].

2.3 Exogenous death receptor pathway

Tsev neeg tuag receptor (DR) nyob rau saum npoo ntawm paj hlwb belongs rau superfamily ntawm qog necrosis factor receptors (TNFR). Qhov chaw tuag (DD) yog tsim los ntawm cov khoom seem thiab muaj cov haujlwm ntawm hydrolyzing protein. Thaum qhov kev tuag receptor khi rau ib qho kev tuag ligand, nws tau txais ib qho kev tuag ntawm lub cev, ua rau lub cev apoptosis hauv lub cev, thiab induces apoptosis.

Tam sim no, paub txog kev tuag receptor ligands feem ntau suav nrog Fas-FasL, TNFR1-TNF, TRAILR1-TRAIL, TRAILR2-TRAIL, thiab DR3-TL1A. Txoj kev kawm zoo txog kev tuag receptor signaling pathways yog Fas, TNFR1, thiab TRAIL[8]. Kev pib ntawm Fas-FasL-mediated apoptosis nyob rau sab nraud txoj kev tuag receptor thaum FasL homotrimeric complex khi rau Fas; TNF trimer binding rau TNFR1 induces qhov kev tuag ntawm TNFR1 los sau cov proteins adapter TRADD, TRADD Signaling molecules xws li TRAF2, RIP, thiab FADD tuaj yeem nrhiav tau.

TRAF2 thiab RIP tuaj yeem qhib NF-κB thiab JNK / AP txoj kev taw qhia, thaum FADD tuaj yeem qhib qhov Caspase cascade cov tshuaj tiv thaiv. Qhov sib txawv ntawm kev nrhiav neeg ua haujlwm ntawm cov khoom siv hluav taws xob los ntawm adapter protein TRADD txiav txim siab txog kev muaj sia nyob lossis muaj sia nyob ntawm cov hlwb. Tuag; TRAILR1 thiab TRAILR2 tau qhia ntau heev hauv cov qog nqaij hlav cancer.

Tom qab khi rau ligand TRAIL, lawv khi rau FADD los ntawm qhov chaw tuag, nrhiav pro-caspase8, thiab daim ntawv DISC. Pro-caspase8 nyob rau hauv DISC tus kheej-cleaves rau hauv active Caspase8, thiab Caspase8 activates Caspase3 los ntawm ib tug Caspase txoj kev zoo ib yam li Fas thiab ib tug mitochondria-dependent txoj kev, yog li kho apoptosis [9].

Cov ntsiab lus

Kev raug mob los ntawm cerebral ischemia-reperfusion yog tsim los ntawm ntau yam txheej txheem nyuaj. Kab lus no tsuas yog tham txog ib feem me me ntawm neuronal apoptosis. Tam sim no, muaj ntau txoj kev tshawb fawb txog kev raug mob ntawm cerebral ischemia-reperfusion raug mob hauv tsev thiab txawv teb chaws, suav nrog kev siv tshuaj suav tshuaj los yog acupuncture cov ntsiab lus los tswj cov proteins uas muaj feem xyuam thiab cov kev taw qhia hauv ntau txoj hauv kev los kho cov paj hlwb thiab ua kom lub hlwb puas. kev tiv thaiv zoo [10]. Txawm li cas los xij, cov txheej txheem ntawm kev ua ntawm cov txheej txheem kev kho mob tseem tsis tau paub meej, thiab ntau qhov kev tshawb fawb soj ntsuam tseem xav tau kom ua tiav cov txiaj ntsig tshiab sai li sai tau los pab cov neeg mob.

Wlub kaus mom yog lub tshuab ntawm Cistanche txoj kev kho mob ischemia-reperfusion raug mob?

Cistanche yog tshuaj ntsuab tshuaj ntsuab uas tau siv nyob rau hauv Suav teb rau ntau pua xyoo. Nws muaj ob peb lub tebchaw bioactive, suav nrog echinacoside, acteoside, thiab verbascoside, uas tau pom tias muaj cov tshuaj tua kab mob antioxidant, tiv thaiv kev mob, thiab kev tiv thaiv kab mob.

Cov kev tshawb fawb tau pom tias Cistanche tuaj yeem tiv thaiv kev raug mob ischemia-reperfusion los ntawm inhibiting oxidative stress, o, thiab apoptosis. Nws ua qhov no los ntawm kev ua kom muaj zog ntawm cov enzymes antioxidant xws li catalase, superoxide dismutase, thiab glutathione peroxidase thaum txo qis kev tsim cov pa oxygen reactive (ROS) thiab lipid peroxidation.

Tsis tas li ntawd, Cistanche tuaj yeem cuam tshuam qhov kev qhia ntawm cov cytokines pro-inflammatory xws li TNF- , IL-1 , thiab IL-6, thiab txo cov neeg ua haujlwm ntawm neutrophils thiab macrophages mus rau qhov chaw raug mob. Los ntawm kev hloov kho lub cev tiv thaiv kab mob, Cistanche tuaj yeem tiv thaiv cov ntaub so ntswg puas tsuaj ntxiv thiab txhawb kev kho cov ntaub so ntswg. Zuag qhia tag nrho, Cistanche siv nws cov txiaj ntsig zoo ntawm ischemia-reperfusion raug mob los ntawm ntau lub tswv yim, ua rau nws muaj kev vam meej rau kev txhim kho cov tshuaj kho tshiab rau tus mob no.

Cov ntaub ntawv

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[2] Peng Zhiyuan, Liu Wanghua, Cao Wen. Kev tshawb nrhiav kev nce qib ntawm cov txheej txheem ntawm apoptosis hauv cerebral ischemia-reperfusion raug mob [J]. Suav Journal of Traditional Chinese Medicine, 2017,35(08):1957-1961.

[3] Bao Li, Zhang Zheng. Kev tshawb nrhiav kev nce qib ntawm apoptosis hauv cerebral ischemia-reperfusion raug mob [J]. Phau ntawv Journal of Practical Medicine, 2009,25(03):487-489.

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[5] Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms tom qab cerebral ischemia ［J］ Stroke, 2009, 40(5): e331-9.

[6] Boujrad H, Gubkina O, Robert N, et al. AIF-mediated programmed necrosis: txoj kev tswj hwm kom tuag ［J］－. J Cell Cycle, 2007, 6(2):2612-2619.

[7] Solaroglu I, Tsubokawa T, Cahill J, et al. Anti-apoptotic nyhuv ntawm granulocytes colony-stimulating yam tom qab focal cerebral ischemia nyob rau hauv nas. Neuroscience, 2006, 143(4): 965-974.

[8] Nijboer CH, Heijnen CJ, Groenendaal F, et al. Lub luag haujlwm dual lub luag haujlwm ntawm NF-kappaB txoj hauv kev hauv cov menyuam yaus lub hlwb hypoxic-ischemic puas ［J］ Stroke, 2008, 39(9): 2578-2586.

[9] Wajant H, Scheurich P. TNFR1-induced activation of the classical NF-κB pathway[J].The FEBS Journal,2015,278(6):862-876.

[10] Zhou Jiaojiao, Wu Chengting, Li Guo, Zhang Qingping, He Yehui. Kev tshawb nrhiav kev nce qib ntawm cov tshuaj suav tshuaj cuam tshuam rau autophagy los tiv thaiv cerebral ischemia-reperfusion raug mob [J]. Hunan Journal of Traditional Chinese Medicine, 2021, 37(09): 191-194.