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.