川芎嗪与N-乙酰半胱氨酸抑制对比剂肾病大鼠肾小管上皮细胞凋亡的比较

Inhibitory effects of tetramethylpyrazine vs N-acetyl cysteine on apoptosis of tubular epithelial cells in rats with contrast-induced nephropathy

目的评价川芎嗪抑制对比剂。肾病大鼠。肾小管上皮细胞凋亡的效应。方法建立对比剂肾病大鼠模型，分正常组（A）、模型组（B）、N-乙酰半胱氨酸组（C）、川芎嗪组（D）。C、D组在造模前3d每日分别腹腔注射150mg／kgN-乙酰半胱氨酸、80mg／kg川芎嗪。测定肾功能，观察。肾脏病理改变，TUNEL染色检测肾小管上皮细胞凋亡，Western印迹检测肾组织Caspase3表达。结果与A组相比，B组血肌酐、尿素氮、血清胱抑素C明显升高，肾间质水肿、肾小管上皮细胞空泡样变及细胞凋亡（P〈O．01）、Caspase-3蛋白表达增多（P〈0．05）。与B组相比，C、D组血肌酐、尿素氮、血清胱抑素C明显回落，病理改变显著减轻，肾小管上皮细胞凋亡指数显著减少（P〈0．01），Caspase3蛋白表达降低（P〈O．05），C、D组在上述检测中差异不显著（P〉0．05）。结论Caspase3依赖的肾小管上皮细胞凋亡参与了对比剂肾病的发生，川芎嗪通过抑制Caspase3抑制。肾小管上皮细胞凋亡并保护大鼠肾功能，效果与N_乙酰半胱氨酸组相近。

Objective To evaluate the effects of tetramethylpyrazine（TMP） vs N-acetylcysteine （NAC） on apoptosis of tubular epithelial ceils in rats with contrast-induced nephropathy（CIN）. Meth- ods Thirty-two male SD rats were divided into four groups（n = 8/group） .. normal control group （group A）, CIN model group（group B）, NAC treatment group（group C）, and TMP treatment group （group IS））. Rats of groups C and D were daily injected intraperitoneally with 150 mg/kg NAC and 80 mg/kg TMP separately at 3rd day before model establishment. All rats were killed 24 h after injection of contrast media. The kidney injury was assessed by serum creatinine（SCr）, blood urea nitrogen （BUN）, Cystatin C and HE staining. Apoptosis of tubular epithelial cells was detected by using TUNEL staining. Simultaneously. The caspase 3 protein expression was detected by using Western blotting. Results Twenty-four h after injection of contrast media, as compared with group A, SCr, BUN, Cystatin C and Caspase 3 protein expression were significantly increased in group B （P^0. 01 or 0. 05 ）. Pathological changes of renal interstitium were the most serious in group B, which mainly show- ing vacuolar degeneration and apoptosis in tubular epithelial cells （P^0. 01 ）. As compared with group B, SCr,BUN,Cystatin C and Caspase 3 protein expression were significantly decreased（P^0. 01）, pathological changes were significantly alleviated in renal interstitium and apoptosis index（AI） was significantly reduced （P〈0. 01 ） in groups C and D in groups C and D. No significant difference was found between groups C and D（P〉0. 05）. Conclusions Caspase 3-dependent apoptosis in tubular epithelial ceils plays an important role in the pathogenesis of CIN. TMP can inhibit apoptosis of tubular epithelial ceils by inhibiting Caspase 3 expression, which is similar to NAC, thus beneficially protect rats against CIN.