中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
Chinese Journal of Pathophysiology
2015年
11期
2009-2015
,共7页
多腺苷二磷酸核糖聚合酶%米诺环素%后处理%心肌缺血再灌注损伤
多腺苷二燐痠覈糖聚閤酶%米諾環素%後處理%心肌缺血再灌註損傷
다선감이린산핵당취합매%미낙배소%후처리%심기결혈재관주손상
Poly( ADP-ribose) polymerase%Minocycline%Postconditioning%Myocardial ischemia-reperfusion injury
目的：探讨米诺环素后处理能否通过抑制多腺苷二磷酸核糖聚合酶1（ PARP－1）过度活化减轻大鼠心肌缺血／再灌注（ I／R）损伤。方法：结扎大鼠冠状动脉左前降支45 min，再灌注2 h，建立心肌I／R模型。将90只雄性Wistar大鼠随机分为假手术（ sham）组， I／R组，低、高剂量米诺环素组及PARP抑制剂3－氨基苯甲酰胺（3－AB）组。氯化三苯基四氮唑（TTC）和伊文思蓝双染法检测心肌梗死范围，HE 染色观察心肌组织形态学改变， TUNEL法评估心肌细胞凋亡程度，酶联免疫吸附法测定血清肿瘤坏死因子α（ TNF－α）和白细胞介素1β（ IL－1β）含量，Western blot法检测再灌注心肌及外周血白细胞内PARP－1活化产物多腺苷二磷酸核糖（ PAR）的表达。结果：与sham组比较，心肌、外周血白细胞内PAR表达及血清TNF－α、IL－1β含量明显升高。与I／R组比较，米诺环素低、高剂量及3－AB后处理组均能显著减少梗死范围及心肌细胞凋亡程度，同时明显降低心肌、外周血白细胞内PAR表达及血清TNF－α、IL－1β含量。米诺环素高剂量组与3－AB组比较无显著差异。结论：米诺环素后处理可能通过抑制心肌及外周血白细胞PARP过度活化减轻大鼠心肌I／R损伤。
目的：探討米諾環素後處理能否通過抑製多腺苷二燐痠覈糖聚閤酶1（ PARP－1）過度活化減輕大鼠心肌缺血／再灌註（ I／R）損傷。方法：結扎大鼠冠狀動脈左前降支45 min，再灌註2 h，建立心肌I／R模型。將90隻雄性Wistar大鼠隨機分為假手術（ sham）組， I／R組，低、高劑量米諾環素組及PARP抑製劑3－氨基苯甲酰胺（3－AB）組。氯化三苯基四氮唑（TTC）和伊文思藍雙染法檢測心肌梗死範圍，HE 染色觀察心肌組織形態學改變， TUNEL法評估心肌細胞凋亡程度，酶聯免疫吸附法測定血清腫瘤壞死因子α（ TNF－α）和白細胞介素1β（ IL－1β）含量，Western blot法檢測再灌註心肌及外週血白細胞內PARP－1活化產物多腺苷二燐痠覈糖（ PAR）的錶達。結果：與sham組比較，心肌、外週血白細胞內PAR錶達及血清TNF－α、IL－1β含量明顯升高。與I／R組比較，米諾環素低、高劑量及3－AB後處理組均能顯著減少梗死範圍及心肌細胞凋亡程度，同時明顯降低心肌、外週血白細胞內PAR錶達及血清TNF－α、IL－1β含量。米諾環素高劑量組與3－AB組比較無顯著差異。結論：米諾環素後處理可能通過抑製心肌及外週血白細胞PARP過度活化減輕大鼠心肌I／R損傷。
목적：탐토미낙배소후처리능부통과억제다선감이린산핵당취합매1（ PARP－1）과도활화감경대서심기결혈／재관주（ I／R）손상。방법：결찰대서관상동맥좌전강지45 min，재관주2 h，건립심기I／R모형。장90지웅성Wistar대서수궤분위가수술（ sham）조， I／R조，저、고제량미낙배소조급PARP억제제3－안기분갑선알（3－AB）조。록화삼분기사담서（TTC）화이문사람쌍염법검측심기경사범위，HE 염색관찰심기조직형태학개변， TUNEL법평고심기세포조망정도，매련면역흡부법측정혈청종류배사인자α（ TNF－α）화백세포개소1β（ IL－1β）함량，Western blot법검측재관주심기급외주혈백세포내PARP－1활화산물다선감이린산핵당（ PAR）적표체。결과：여sham조비교，심기、외주혈백세포내PAR표체급혈청TNF－α、IL－1β함량명현승고。여I／R조비교，미낙배소저、고제량급3－AB후처리조균능현저감소경사범위급심기세포조망정도，동시명현강저심기、외주혈백세포내PAR표체급혈청TNF－α、IL－1β함량。미낙배소고제량조여3－AB조비교무현저차이。결론：미낙배소후처리가능통과억제심기급외주혈백세포PARP과도활화감경대서심기I／R손상。
AIM:To investigate whether minocycline postconditioning protects rat myocardium from ischemia-reperfusion ( I/R ) injury through attenuating poly ( ADP-ribose ) polymerase-1 ( PARP-1 ) excessive activation. METHODS:The left anterior descending coronary artery was ligated for 45 min and then reopened for 2 h to establish the rat model of myocardial ischemia-reperfusion injury.The male Wistar rats ( n =90 ) were randomly divided into sham group, I/R group, low-and high-dose minocycline groups, and 3-aminobenzamide (3-AB, PARP inhibitor) group.The myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride ( TTC) staining.The morpho-logical changes of the myocardium were observed with HE staining.The cardiomyocyte apoptosis was detected using in situ TDT-mediated dUTP nick end labeling ( TUNEL) .The level of tumor necrosis factorα( TNF-α) and interleukin 1β( IL-1β) in the serum were measured by ELISA.The content of poly( ADP-ribose) ( PAR) in the reperfused myocardium and peripheral leukocytes were detected by Western blot.RESULTS: Compared with sham group, PAR expression, TNF-αcontent and IL-1βconcentration increased in all other groups.Compared with I/R group, treatment with low and high doses of minocycline and 3-AB significantly reduced the infarct size and myocardial apoptosis.PAR expression, TNF-αcontent and IL-1βconcentration in low-and high-dose minocycline groups and 3-AB group all decreased.No significant difference of the above parameters between high-dose minocycline group and 3-AB group was observed.CONCLUSION: Minocy-cline postconditioning may attenuate myocardial ischemia-reperfusion injury by depressing the activation of PARP-1 in car-diomyocytes and peripheral leukocytes in rats.
