川芎嗪对大鼠肾脏缺血/再灌注损伤保护作用及抗细胞凋亡作用  

Protective and anti-apoptosis effects of Ligustrazine on rat kidney of ischemia/reperfusion injury in vitro

作　　者：王汉民[1] 谭华[2] 赵洪雯[1] 张鹏[2] 黄朝晖[1] 何丽洁[2] 陈光磊[2] 吴雄飞[1] 

机构地区：[1]第三军医大学西南医院肾脏内科,重庆400038 [2]第四军医大学西京医院肾脏内科,陕西西安710033

出　　处：《第四军医大学学报》2008年第9期833-836,共4页Journal of the Fourth Military Medical University

摘　　要：目的:探讨川芎嗪对缺血/再灌注(I/R)损伤大鼠肾功能、肾脏组织形态学、细胞凋亡及相关基因表达的影响.方法:将大鼠随机分为假手术(S)组、I/R组、再灌注后给予川芎嗪(TMP-post)组、再灌注前给予川芎嗪(TMP-pre)组,各组分别采用化学法测定血尿素氮和肌酐,光镜和电镜观察肾组织形态学变化,原位末端标记法检测肾脏细胞凋亡指数,免疫组化和免疫印迹法检测肾脏Bcl-2和Bax蛋白的表达.结果:TMP-pre组较I/R组血尿素氮和肌肝显著降低,肾小管损伤评分减轻,分别为[(21.8±5.2)vs(31.1±4.4)mmol/L,P<0.01)],[(196±55)vs(295±64)μmol/L,P<0.01)],[(372±46)vs(563±62),P<0.01)];肾小管上皮细胞损伤及超微结构改变明显减轻,肾组织凋亡细胞数明显减少[(13.6±2.9)vs(28.8±4.6),P<0.01)];Bcl-2蛋白表达明显增强[(1.15±0.12)vs(0.88±0.12),P<0.05)],Bax表达明显减弱[(0.87±0.11)vs(1.15±0.09),P<0.05)].结论:川芎嗪可明显减轻I/R肾损伤,其保护作用机制与Bcl-2蛋白表达增强和Bax蛋白表达减弱介导的肾脏细胞凋亡有关.AIM： To explore Ligustrazine （ Tetramethylpyrazine, TMP） on the effect of in rats wit rat renal functions, renal tissue morphology, cell apoptosis and expressions of related genes in rats with. METHODS： Forty Wistar rats of either sex were randomly divided into 4 groups, which were sham operation（n = 10）, I/R model（n = 10）, TMP-post （n = 10, intraperitoneal TMP 32 rag/ kg per 6 h after reperfusion for 30 min） and TMP-pre （n = 10, intraperitoneal TMP 32 mg/kg at 45 min, 8, 16, 24 h before ischemia） groups. Blood urea nitrogen and creatinine were detected by chemical method. Renal cell apoptotic index was examined by means of terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling（TUNEL）. The expressions of Bcl-2 and Bax in kidney was immunohistochemically evaluated and quantified by Western Blot analysis. The kidney histology were observed by light and electron microscope. RESULTS： Compared with those in the TMP-pre group, the blood urea nitrogen[ （21.8 ±5.2）vs （31.1 ±4.4） mmol/L,P 〈0.01 ], the creatinine [ （ 196 ± 55） vs （ 295 ±64） p, mol/L,P 〈0.01 ） ] and the score of injury in renal tubules [（372±46） vs （563 ±62）,P〈0.01） ] were decreased significantly in I/R group. The changes of injury and ultrastructure in tubular epithelial cells were significantly attenuated in TMP-pre group. By Tetramethylpyrazine pre-treatment, the apoptotic index （13.6 ±2.9 vs 28.8 ±4.6, P〈0.01） and the expression of Bax （ 0.87 ± 0.11 vs 1.14 ± 0.09, P 〈 0.05 ） were decreased significantly, and the expression of Bcl-2（ 1.15 ±0.12 vs 0. 88 ± 0. 12, P 〈 0. 05） was increased significantly as compared with that in I/R group. CONCLUSION： Tetramethylpyrazine can attenuate kidney I/R injury, and protective mechanism may be partly through inhibition of cell apoptosis by regulating the expressions of apoptosis-related genes Bcl-2 and Bax.

关 键 词：川芎嗪 肾脏 再灌注损伤 细胞凋亡 保护 

分 类 号：R691[医药卫生—泌尿科学] R286[医药卫生—外科学]