大鼠肢体缺血再灌注后骨骼肌细胞凋亡及其BQ123的保护作用  

Protective effects of BQ123 on skeletal muscle apoptosis following ischemia reperfusion of rat hind limbs

作　　者：刘燕[1] 张连元[1] 

机构地区：[1]河北联合大学基础医学院机能实验室,河北唐山063000

出　　处：《西安交通大学学报（医学版）》2011年第4期414-416,共3页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：河北省教育厅科研基金资助课题(No.2001135)~~

摘　　要：目的观察大鼠肢体缺血再灌注(LIR)后骨骼肌细胞凋亡情况,探讨内皮素A(ETA)受体拮抗剂BQ123对其的保护机制。方法雄性Wistar大鼠随机分为3组(n=8):对照组、肢体缺血再灌注组和选择性ETA受体阻断剂BQ123处理组,缺血4 h再灌注4 h后检测血浆一氧化氮(NO)、内皮素(ET-1)、血栓素B2(TXB2)、前列环素(6-Keto-PGF1α)的含量以及NO/ET-1比值、TXB2/6-Keto-PGF1α比值的变化;采用免疫组织化学方法检测腓肠肌组织中凋亡相关基因Bcl-2、Bax和凋亡蛋白酶(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。结果再灌注组与对照组相比较,血浆NO、ET-1、TXB2、6-Keto-PGF1α含量均增加,但TXB2/6-Keto-PGF1α比值增大,NO/ET-1比值减小,凋亡指数(AI)明显增高,Bax、Bcl-2、Caspase-3蛋白表达明显较对照组增强,但Bcl-2/Bax比值减小;与再灌注组比较,BQ123处理组血浆NO、6-Keto-PGF1α含量升高,ET-1、TXB2下降,NO/ET-1比值升高,TXB2/6-Keto-PGF1α比值下降;腓肠肌组织Bcl-2/Bax比值升高,Caspase-3表达水平明显减弱,AI下降。结论 ETA受体拮抗剂BQ123可减轻大鼠肢体缺血再灌注后骨骼肌细胞凋亡。Objective To observe apoptosis of skeletal muscle 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 L1R. Methods Male Wistar rats were randomly divided into three groups （ n ： 8） ： control group, LIR group and endothelin-A receptor antagonist BQ123 treated group. The contents of nitric oxide （NO）, endothelin-1 （ET-1）, thromboxane B2 （TXBz）, 6-Keto-prostaglandin FI,,（6-Keto-PGF1a） as well as NO/ET-1 and TXB2/6- Keto-PGFIo in plasma were measured after 4-hour ischemia and 4-hour reperfusion, lmmunohistochemistry （IHC） method was used to detect the protein expressions of Bcl-2, Bax and Caspase-3. Apoptosis was examined by TdT-mediated dUTP nick end labeling （TUNEL）, respectively. Results Compared with those in control group, the values of NO, ET-1, TXB2 and 6-Keto-PGF1a, in plasma were all increased significantly in LIR group. The level of TXB2/6-Keto-PGF1a increased while the level of NO/ET-1 decreased. The apoptosis index was significantly higher in LIR group. The expressions of Bcl-2, Bax and Caspase-3 were upregulated more significantly in L1R group, but the ratio of Bcl-2/Bax was lower. Compared with those in LIR group, the contents of NO, 6-Keto-PGF1a and the ratio of NO/ET-1 in plasma were increased, the level of ET-I and the ratio of TXB2/6-Keto-PGF1a in plasma were decreased in BQ123 treated group. The ratio of Bcl-2/Bax in gastrocnemius tissue was obviously increased, but the expression of Caspase-3 was obviously decreased in BQ123 treated group. Apoptosis index in BQ123 treated group was lower than that in LIR group. Conclusion The endothelin-A receptor antagonist BQ123 can relieve the apoptosis of skeletal muscle following LIR injury in rats.

关 键 词：再灌注损伤 骨骼肌 内皮缩血管肽1 凋亡 

分 类 号：R363[医药卫生—病理学]