摘要
目的:观察大鼠肢体缺血再灌注(LIR)后骨骼肌损伤和细胞凋亡情况,探讨内皮素A(ETA)受体拮抗剂BQ123对大鼠LIR损伤的保护机制。方法:24只雄性Wistar大鼠随机分为3组(n=8):对照组、缺血再灌注(IR)组和BQ123+IR组,检测各组大鼠血浆乳酸脱氢酶(LDH)、肌酸激酶(CK)、丙二醛(MDA)、一氧化氮(NO)、内皮素1(ET-1)的含量以及NO/ET-1比值;测定腓肠肌组织中MDA、髓过氧化物酶(MPO)、NO、ET-1、NO/ET-1比值及腓肠肌DNA双链百分率;采用免疫组织化学方法检测腓肠肌组织中凋亡蛋白酶Caspase-3的蛋白表达情况;利用原位脱氧核糖核甘酸末端转移酶介导的缺口末端标记法(TUNEL)检测各组腓肠肌细胞的凋亡情况。结果:与IR组比较,BQ123+IR组血浆LDH、CK、MDA明显降低(P<0.01),血浆NO升高(P<0.01),ET-1下降(P<0.01),NO/ET-1比值升高(P<0.01)。与IR组比较,BQ123+IR组腓肠肌组织MDA、MPO、ET-1含量下降(P<0.01),NO、NO/ET-1及DNA双链百分率值升高(P<0.05或P<0.01);腓肠肌组织Caspase-3表达水平明显减弱,凋亡指数(AI)下降(P<0.01)。结论:ETA受体拮抗剂BQ123可减轻大鼠LIR后骨骼肌损伤和细胞凋亡。
Objective To observe the injury of skeletal muscle and apoptosis following limb ischemia reperfusion (LIR) in rats and investigate the protective mechanism of endothelin-A receptor antagonist BQ123 on the injury of skeletal muscle following LIR. Methods Male Wistar rats were randomly divided into three groups (n= 8) = control group, IR group, BQ123-FIR group. The contents of lactate dehydrogenase (LDH), creatine phosphate kinase (CK), malondialehyde (MDA), initric oxide (NO), endothelin-1 (ET-1), and NO/ET-1 in plasma and the values of MDA, myeloperoxide (MPO), NO, ET-1, NO/ET-1, the percentage of DNA Chain% in gastrocnemius tissues were measured. Immunohistochemistry (IHC) method was used to detect the expression of Caspase-3 in gastrocnemius tissues. Apoptosis was examined by means of TdT-mediated dUTP nick end labeling (TUNEL). Results Compared with IR group, the levels of LDH, CK, MDA, ET-1 in plasma in BQ123+IR group were decreased (P^0.01); the content of NO in plasma and the percentage of NO/ET1 were increased (P〈0.01), but the expression of Caspase 3 was obviously decreased (P〈0.01) ; the contents of MDA, MPO, ET-1 in gastroenemius tissues were decreased (P〈0.01), the NO level, NO/ET-1, and the percentage of DNA chain were increased (P〈0.05 or P〈0.01) ; the expression of Caspase-3 in gastrocnemius tissues was signfieantly decreased, and the apoptotic index (AI) in BQ123-LIR group was also decreased (P〈0.01). Conclusion The endothelin-A receptor antagonist BQ123 hase protective effects on skeletal muscle injury and apoptosis following LIR in rats.
出处
《吉林大学学报(医学版)》
CAS
CSCD
北大核心
2010年第1期131-134,共4页
Journal of Jilin University:Medicine Edition
基金
河北省教育厅科研基金资助课题(2001135)