川芎嗪对顺铂肾损伤大鼠肾细胞凋亡及凋亡相关蛋白表达的影响  

Effects of ligustrazine on renal cell apoptosis and expression of apoptosis-related proteins in rats with cisplatin-induced renal injury

作　　者：刘晓华[1] 黎七雄[1] 

机构地区：[1]武汉大学医学院药理学系,湖北武汉430071

出　　处：《中国药理学与毒理学杂志》2005年第5期352-356,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的探讨川芎嗪(TMP)对顺铂(DDP)大鼠肾毒性有无保护作用。方法DDP8mg·kg-1ip诱导大鼠肾损伤,于给予DDP2d前大鼠分别ip50,100mg·kg-1·d-1TMP,连续5d,于给药d5收集各组大鼠尿液,测24h尿蛋白含量,并于末次给药后4h处死大鼠,测血清尿素氮(BUN)和肌酐(Cr)含量,采用原位缺口末端标记法检测肾脏细胞凋亡,免疫组化SP法检测肾脏Bax和Bcl2蛋白表达水平。结果50,100mg·kg-1TMP组可降低DDP所致大鼠24h尿蛋白及血清BUN和Cr含量的升高(P<0.01);TMP两剂量组也可明显减少肾脏细胞凋亡率(P<0.01),显著增强肾脏凋亡相关蛋白Bcl2的表达,减少Bax表达,并明显降低Bax/Bcl2比值(P<0.01)。结论TMP可能通过降低凋亡相关蛋白Bax和增强Bcl2的表达,并降低Bax/Bcl2比值而抑制DDP引起的肾细胞凋亡,使肾脏免受损伤的作用。AIM To investigate whether ligustrazine can protect rats from nephrotoxicity induced by cisplatin （ DDP ）. METHODS Nephrotoxicity was induced in rats by intraperitoneal injection of DDP （ 8 mg·kg^-1）. Ligustrazine （50,100 mg·kg^-1·d^-1） was administered daily by gavage 2 d before the DDP injection for 5 d. The 24 h urine samples were collected for measuring the content of urinary protein on d 5 ligustrazine injection and the rats were sacrificed 4 h after the last injection, blood urea nitrogen（BUN） and serum creatinine （Cr） were tested. Apoptosis was evaluated by terminal dexoynucleotide transferase mediated d-UTP-biotin nick end labeling. Immunohistochemistry was used to detect the protein expression level of Bax and Bcl-2. RESULTS The content of BUN, Cr and 24 h-urinary protein in rats given ligustrazine were significantly lower than those in rats treated with DDP （P〈0.05, P〈0.01）. Ligustrazine could significantly decline the apoptosis rate of renal cells, increase the expression of Bcl-2 and decline the exprssion of Bax. And the Bax/Bcl-2 ratio was declined significantly by ligusrazine （P〈0.01）. CONCLUSION Ligustrazine can suppress renal cell apoptosis induced by DDP and protect renal from injury by means of increasing the expression of Bcl-2 and declining the expression of Bax and Bax/Bcl-2 ratio.

关 键 词：川芎嗪 顺铂 毒性 凋亡 蛋白BAX 蛋白Bel-2 

分 类 号：R285[医药卫生—中药学]