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

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。

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

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.