Puas yog Glycosides Ntawm Cistanche tuaj yeem siv los kho Cardiotoxicity?

Kev tiv thaiv zoo ntawm glycosides ntawm cistanche tawm tsam doxorubicin-induced cardiotoxicity hauv cov nas.

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

Wu Liya, Wang Xiaowen, Wang Xuefei, et al

( Department of Pharmacology, X Xinjiang Medical University, X Xinjiang 830054)

Abstract: Lub Hom Phiaj: Tshawb nrhiav kev tiv thaiv ntawmglycosides ntawm cistanche(GCs) tiv thaiv doxorubicin-inducedcardiotoxicitynyob rau hauv nas thiab nws cov mechanism.

Txoj kev: NI H nas tau kho intraperitoneally nrog doxorubicin ( Dox ) ntawm ib koob ntawm 17. 5 mg / kg - 1 los tsim tus qauv mob myocardium raug mob. Kev ua haujlwm ntawm SOD, GS H-Px, cov ntsiab lus ntawm M DA, thiab cov haujlwm ntawm creatine phosphokinase (CPK) raug ntsuas. Kev hloov pauv ntawm lub plawv ultrastructural tau kuaj nrog lub tshuab ntsuas hluav taws xob.

Cov txiaj ntsig: Thaum 48h tom qab kev tswj hwm, Dox tau tshem tawm qhov kev puas tsuaj loj ntawm myocardial nrog txo kuv cov oca radial SOD thiab GS H-Px kev ua haujlwm, nce myocardial M DA cov ntsiab lus thiab cov ntshav CPK hauv cov nas. Nws kuj ua rau mob myocardial cell puas tsuaj ntawm qib ultrastructure. Kev tswj hwm qhov ncauj ntawm GCs (62. 5, 125, 250 mg / kg- 1 ) tiv thaiv cov kev hloov pauv no los ntawm Dox, los ntawm kev ua kom myocardial SOD, GS H-Px kev ua, txo qis myocardial M DA cov ntsiab lus, thiab ntshav CPK kev ua haujlwm. , thiab txocardiotoxicityo Dox ntawm qib ultrastructural.

Xaus: TheGlycosides ntawm Cistanchemuaj kev tiv thaiv zoo raucardiotoxicityinduced los ntawm Dox. Cov txheej txheem ntawm kev txo qis cardiotoxicity tshwm sim los ntawm Dox tuaj yeem nyob ntawm qhov cuam tshuam ntawm GCs ntawm kev tshem tawm ox yg thiab dawb radicals hauv nas plawv, tiv thaiv kev ua haujlwm ntawm SO D thiab GSH-Px, thiab inhibiting lipid peroxidation.

Ntsiab lus: doxorubicin;glycosides ntawm cistanche; lipid peroxidation;cardiotoxicity; creatine phosphokinase; ultrastructure

Doxorubicin (Dox) yog ib qho tshuaj tua kab mob anthraquinone thiab muaj txiaj ntsig zoo rau ntau hom qog nqaij hlav. Txawm li cas los xij, vim nws qhov mob hnyav thiab mob ntev myocardial toxicity, nws txwv kev siv dav hauv Dox hauv kev kho mob. Nws paub tias cov nyhuv tiv thaiv qog ntawm Dox yog cuam tshuam rau DN A replication thiab RN A synthesis, thiab nwscardiotoxicitymuaj feem xyuam rau lipid peroxidation puas tsuaj los ntawm semiquinone adriamycin [1, 2]. Yog li ntawd, nws yog ib qho tseem ceeb kom nrhiav tau dawb radical scavengers thiab antioxidants los antagonizecardiotoxicityntawm Dox thaum khaws nws cov haujlwm tiv thaiv qog.Cistanchecistanche tag nrho glycosides (GCs) yog cov khoom xyaw nquag muab rho tawm los ntawmCistanche. Cov kev tshawb fawb cuam tshuam tau pom tias GCs muaj cov teebmeem antioxidant ntawm cov ntaub so ntswg nas, tuaj yeem txo cov lipofuscin cov ntsiab lus [3], muaj kev tiv thaiv ntawm nas myocardial ischemia [4], thiab muaj kev tiv thaiv lipid peroxidation thiab tiv thaiv hluav taws xob. [5]. Txoj kev tshawb no tsom mus tshawb nrhiav cov txiaj ntsig tiv thaiv thiab cov txheej txheem ntawm GCs ntawm kev raug mob myocardial hauv cov nas raug ntxias los ntawm Dox.

1 Cov khoom siv thiab cov txheej txheem

1. 1 Tshuaj thiab tshuaj reagents

GCs tau muab rho tawm los ntawm kev ua ntsevCistanchenyob rau sab qaum teb Xinjiang. Cov khoom xyaw tseem ceeb yog phenethyl cawv glycosides xws li echinacoside thiab ergot glycosides (muab los ntawm Department of Natural Medicine Chemistry, School of Pharmacy, Xinjiang Medical University); Tetramethoxypropane (TM P Sigma Tuam Txhab); Doxorubicin (Do x, Zhejiang Hisun Pharmaceutical Co., Ltd.); Vitamin E (Vit E, Shanghai Yan'an Pharmaceutical Factory); Lwm cov reagents yog tsim nyob rau hauv domestic.

glycosides ntawm cistanche cov nyhuv ntawm cardiotoxicity

1. 2 Cov khoom siv sim

721 hom spectrophotometer (Shanghai Thib Peb Kev Ntsuas Ntsuas Lub Hoobkas); O LYM PU S microscope (ua hauv Nyij Pooj); JEM-100CXII kis tau tus mob electron microscope (ua hauv Nyiv); PHS -250 hom acidity meter (Shanghai Lei Sib Nqus Tshuab Hoobkas).

1. 3 Tsiaj pab pawg thiab kev tswj hwm

N IH nas tau muab los ntawm Animal Experiment Center of Xinjiang Institute of Endemic Diseases, thiab lub chaw kuaj mob kuaj tsiaj daim ntawv pov thawj tus lej: No. {{0}}. 138 N IH nas raug xaiv, hnyav (24 ± 2) g, ib nrab txiv neej thiab poj niam. Random muab faib ua 6 pawg (23 hauv txhua pab pawg): (1) Cov pab pawg tswj: ib txwm saline (NS) 20 ml / kg; (2) Dox raug mob pawg: NS 20 ml / kg; (3) Vit E pawg: Vito 100 mg / kg; (4) GCsⅠ pawg: GCs 62.5 mg/kg; (5) GCsⅡ pawg: GCs 125.0 mg/kg; (6) GCsⅢ pab pawg: GCs 25.0 mg / kg, tag nrho cov pab pawg saum toj no tau tso dej rau hauv plab, ib hnub ib zaug. Dox raug mob pawg, Vit E pawg, GCsⅠ pab pawg, GCsⅡ pab pawg, GCsⅢ pawg tau txhaj tshuaj intraperitoneally nrog Dox 17. 5 mg / kg rau hnub 4 tom qab kev tswj hwm ntawm NS thiab GCs. Tom qab 48 teev, cov pob muag raug tshem tawm kom sau cov ntshav, cov ntshav tau npaj, thiab cov tsiaj tau muab txi tam sim ntawd tshem tawm lub plawv, yaug nrog NS, blotted qhuav nrog ntawv lim, thiab hnyav. Tom qab 30 feeb, coj tus supernatant los ntsuas cov ntsuas biochemical. Muaj 3 nas nyob rau hauv txhua pab pawg, thiab lub siab raug coj mus ua electron microscopy specimens.

1.4 Kev txiav txim siab ntawm biochemical ntsuas

Txoj kev pyrogallol autooxidation [6] tau siv los txiav txim siab txog kev ua haujlwm ntawm myocardial superoxide dismutase (SOD); txoj kev DTNB [7] tau siv los txiav txim siab txog kev ua haujlwm ntawm myocardial selenium-glutathione peroxidase (Se-GS H-Px); Siv TBA txoj kev [8] los txiav txim cov ntsiab lus ntawm myocardial lipid peroxidation khoom malondialdehyde (M DA ); protein kom muaj nuj nqis siv CBB-SDS txoj kev [9]; siv CPK txoj kev [10] los txiav txim siab cov ntshav creatine phosphokinase (CPK).

1.5 Electron microscopy ntawm myocardial cov ntaub so ntswg

Lub apex ntawm lub plawv tau kho ob zaug nrog 4 feem pua ​​glutaraldehyde thiab 1 feem pua ​​osmium acid, lub cev qhuav dej nrog acetone, embedded nyob rau hauv Epon 812, stained nrog lead-uranium electrons, thiab soj ntsuam raws li ib tug JEM -100CXII kis electron microscope. 1.6 Statistical processing Tag nrho cov ntaub ntawv yog qhia raws li x-± s. Tom qab kev sim cov ntaub ntawv raug sim rau homogeneity ntawm qhov sib txawv, F test thiab q xeem yog siv rau kev ua lej. Kev soj ntsuam qib=0.05.

2 kev tshwm sim

2.1 Kev cuam tshuam ntawm GCs ntawm biochemical indexes ntawm Dox-injured myocardium yog qhia hauv Table 1.

2. 1.1 Cov nyhuv ntawm GCs ntawm SOD kev ua ntawm Dox-injured myocardium

Piv nrog rau pawg tswj hwm, pawg Dox raug mob txo qis myocardial SOD kev ua haujlwm los ntawm 41.1 feem pua ​​(P<0.01). the="" gcsⅰ,="" gcsⅱ,="" gcsⅲ,="" and="" vit="" e="" groups="" increased="" the="" myocardial="" sod="" activity="" by="" 30.9%="" and="" 33.2="" compared="" with="" the="" dox="" injury="" group,="" respectively.="" %,="" 36.5%,="" and="" 34.9%="" (all=""><0.01), the="" gcsⅲ="" group="" was="" close="" to="" the="" control="" group="" (p="">0.05), thiab lwm pab pawg tau qis dua pawg tswj hwm.

2.1.2 Cov nyhuv ntawm GCs ntawm kev ua ntawm Se-GSH-Px hauv myocardium puas los ntawm Dox

Piv nrog rau pawg tswj hwm, pawg Dox raug mob tau txo qis myocardial Se-GSH-Px kev ua haujlwm los ntawm 26.2 feem pua ​​(P<0.01), and="" the="" gcsⅰ,="" gcsⅱ,="" gcsⅲ,="" and="" vit="" e="" groups="" increased="" by="" 19.="" 2%="" and="" 21="" respectively="" compared="" with="" the="" dox="" injury="" group.="" .1%,="" 25.0%="" and="" 26.1%="" (all=""><0.01), which="" are="" all="" close="" to="" the="" control="" group="" (p="">0.05).

2.1.3 Kev cuam tshuam ntawm GCs ntawm cov ntsiab lus ntawm M DA hauv Dox-injured myocardium

Piv nrog rau pawg tswj hwm, MDA cov ntsiab lus ntawm Dox raug mob pawg tau nce 25.8 feem pua ​​(P<0.01), and="" the="" gcsⅰ,="" gcsⅱ,="" gcsⅲ,="" and="" vit="" e="" groups="" decreased="" by="" 16.7%,="" 17.3%,="" and="" 18.="" 6%="" and="" 17.3%="" (both=""><0.01), both="" were="" close="" to="" the="" control="" group="" (p="">0.05).

glycosides ntawmcistanche

2.1.4 Cov txiaj ntsig ntawm GCs ntawm kev ua haujlwm ntawm cov ntshav C PK hauv Dox cov nas raug mob

Serum CPK kev ua hauv pawg Dox raug mob tau nce 87.3 feem pua ​​​​piv rau cov pab pawg ib txwm (P<0.01), and="" the="" gcsⅰ,="" gcsⅱ,="" gcsⅲ,="" and="" vit="" e="" groups="" were="" reduced="" by="" 26.6%,="" 33.1%,="" and="" 37="" respectively="" compared="" with="" the="" dox="" injury="" group.="" .="" 4%="" and="" 36.="" 7%="" (both=""><0.01), both="" higher="" than="" the="" control="">

Table 1 Cov nyhuv ntawm GCs ntawm biochemical indexes ntawm Dox raug mob myocardium

Lus Cim: Piv nrog rau pawg tswj hwm, * * P<0.01; compared="" with="" the="" dox="" injury="" group,="" #="" #="" p=""><>

2.2 Electron microscopy ntawm nas myocardium

2. 2. 1 Tswj pawg

Lub myocardial fiber ntau tsis zoo, cov myofibrils tau teeb tsa kom zoo, cov sarcomere bands tau teeb tsa, mitochondria tau teeb tsa zoo, cov qauv zoo li qub, thiab cov qauv nuclear yog qhov qub.

2. 2. 2 Dox puas pab pawg

Nws tuaj yeem pom tau tias muaj cov kev hloov pauv pom tseeb hauv cov txheej txheem ntawm myocardial fibers, myocardial hlwb yog o, intracytoplasmic sarcomere loj hlob, lub ci band widens, txawv txav bands tshwm nyob rau hauv qee qhov chaw, thiab cov khoom Z-line nce. Mitochondria tau diffusely o thiab hyperplastic, nrog sparse cristae kev npaj, pob txha, thiab vacuolar degeneration. Lub sarcoplasmic reticulum nthuav dav, theem nrab lysosomes nce, thiab focal degeneration tuaj yeem pom. Lub ntim nuclear nce thiab qhov chaw perinuclear widens.

2. 2. 3 GCsⅠ pawg

Myocardial fiber ntau o tau raug txo. Cov qauv sarcomere yog qhov qub, tab sis cov sarcomere tseem dav dua li pawg tswj hwm. Mitochondrial o tau txo qis, matrix ceev nce, cristae ceev nce, thiab tus kheej mitochondrial cristae tseem hloov. Kev nce qib theem nrab lysosomes hauv cytoplasm.

2. 2. 4 GCs Ⅱ thiab Ⅲ pawg

Cov qauv myocardial fiber ntau rov qab mus rau qhov qub. Cov myofibrils tau npaj kom zoo, cov qauv sarcomere yog qhov qub, thiab cov qauv mitochondrial rov zoo li qub.

3 Kev sib tham

Dox yog ib qho tshuaj tua kab mob anthraquinone, uas muaj cov yam ntxwv ntawm cov qog nqaij hlav dav dav thiab muaj zog. Txawm li cas los xij, Dox tuaj yeem ua rau mob myocardial toxicity, xws li ntau yam arrhythmias nyob rau theem pib ntawm cov tshuaj, kev siv tshuaj, thiab mob plawv tsis ua hauj lwm nyob rau theem kawg, uas txwv tsis pub nws daim ntawv thov kev kho mob. Lub mechanism ntawm Dox ua rau myocardial toxicity yog feem ntau yog zus tau tej cov ntau reactive oxygen dawb radicals uas ua rau myocardial puas. Qhov kev sib raug zoo ntawm Dox nrog cov ntaub so ntswg myocardial yog siab dua li ntawm lwm cov ntaub so ntswg. Tom qab nkag mus rau cov hlwb myocardial, nws tau hloov mus rau hauv semiquinone Dox, uas ua rau cov pa oxygen molecules hloov mus rau superoxide anion dawb radicals (O-2), thiab nrog hydrogen peroxide (H2 O2)) tsim. O-2· thiab H2 O2 tsim hydroxyl radicals (OH·) los ntawm Haber-Weiss cov tshuaj tiv thaiv lossis Fento n cov tshuaj tiv thaiv. O-2· thiab OH· sau ntau ntau, uas tuaj yeem ua rau lipid peroxidation hauv cov ntaub so ntswg thiab cell membranes thiab ua rau kev puas tsuaj rau cov macromolecules lom [11].

Nws tau pom nyob rau hauv qhov kev sim uas tom qab 48 teev ntawm intraperitoneal txhaj ntawm Dox (17.5 mg / kg) rau nas, cov kev ua ub no ntawm nas myocardial free radical scavenging enzyme SO D thiab Se-GSH-Px tau txo qis, thiab lipid peroxidation khoom. Cov ntsiab lus ntawm MDA tau nce ntau, thiab kev ua haujlwm ntawm cov ntshav CPK tau nce ntxiv. Nyob rau hauv lub tshuab ntsuas hluav taws xob, lub ultrastructure ntawm lub plawv cov leeg tau raug puas tsuaj, tshwm sim raws li pom tseeb o ntawm mitochondria, fractured cristae, vacuolar degeneration, txo matrix ceev, thiab expansion ntawm sarcoplasmic reticulum.

Txhua pawg koob tshuaj ntawm GCs tuaj yeem ua rau muaj kev ua haujlwm ntawm cov dawb radical scavenging enzymes SOD thiab Se-GS H-Px nyob rau hauv lub plawv cov leeg ntawm Dox-mob mob nas, txo cov ntsiab lus ntawm MDA, thiab txo qhov tso tawm ntawm CPK. Nws tau pom zoo tias GCs tuaj yeem txo qhov lipid peroxidation puas tsuaj los ntawm Do x los ntawm kev ua kom cov enzymes dawb radical scavenging hauv lub cev. GCsⅡ thiab GCsⅢ pawg tau tiv thaiv ultrastructure ntawm myocardial fibers los ntawm Dox puas. Hauv kev tshawb nrhiav vitro siv cov cuab yeej tshuaj ntsuam xyuas chemiluminescence niaj hnub, nws pom tias GCs tuaj yeem tshem tawm cov pa oxygen dawb radicals xws li O·2, OH·, H2O2, thiab cov nyhuv scavenging ntawm O·2 yog qhov tseem ceeb [12]. Nws tau pom zoo tias GCs tuaj yeem tshem tawm O-2· cuam tshuam los ntawm semiquinone Dox hauv myocardium, yog li cuam tshuam cov saw hlau cov tshuaj tiv thaiv ntawm cov dawb radicals thiab ua raws li cov blocker ntawm lipid peroxidation saw.

Hauv qhov kev sim no, Vit E tau siv los ua kev tswj hwm zoo. Cov txiaj ntsig tau pom tias Vit E muaj qee yam kev tiv thaiv ntawm mob myocardial puas tsuaj los ntawm Do x hauv cov nas. Nws tuaj yeem txo cov ntsiab lus ntawm myocardial M DA thiab nce cov haujlwm ntawm SOD thiab Se-GSH-Px. 13] Cov ntawv ceeb toom zoo ib yam.

Lub ntsiab tseem ceeb ntawm GCs yog phenoxyethanol glycosides, thiab cov qauv zoo ib yam li Vit E, uas yog, nws muaj phenolic hydroxyl pawg thiab hydroxyl pawg. Yog li ntawd, nws tau kwv yees tias GCs tuaj yeem muab cov hydrogen atoms ntawm phenolic hydroxyl pawg ntawm nws cov qauv molecular mus rau lipid radical (LOO·), tig mus rau lipohydroperoxide (LOOH), uas yog tom qab ntawd decomposed rau hauv non-toxic hydroxyl los ntawm GSH- Px Nws tiv thaiv peroxidation ntawm unsaturated fatty acids nyob rau hauv biofilm los ntawm dawb radicals, yog li txo qhov kev puas tsuaj ntawm Dox rau cardiomyocytes. Lub tshuab tseem yuav tsum tau kawm hauv qhov tob.

glycosides ntawm cistanche tuaj yeem kho cardiotoxicity

Cov ntaub ntawv

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Los ntawm: Tuam Tsev Qiv Ntawv Suav Number: Q949. 752.7; r978 ua. 1; R-332 Cov ntaub ntawv pov thawj code: A Tshooj xov tooj: 1009-5551 (2003) 01-0028-03

Txoj Haujlwm Pab Nyiaj: Lub Tsev Kawm Txuj Ci Zoo Tshaj Plaws ntawm Xinjiang Uygur Autonomous Region Science thiab Technology Commission (96814)

Hais txog tus sau: Wu Liya Yiming (1964-), poj niam (Uyghur), tus tswv, tus kws qhia ntawv, kev tshawb fawb kev taw qhia: tshuaj kho mob plawv.