川芎嗪对马兜铃酸肾病大鼠肾间质微血管病变的干预研究

The renal interstitial microangiopathy in rats with aristolochic acid nephropathy and the the effects of Ligustrazine intervention

目的探讨川芎嗪对马兜铃酸肾病大鼠肾损害及肾间质微血管病变管周毛细血管（PTC）密度及血管内皮生长因子（VEGF）的变化。方法雄性Wistar大鼠98只分为4组，即模型组、川芎嗪组、苯那普利组各26只，按马兜铃酸（AA）20mg·kg^-1·d^-1灌胃关木通浸膏；对照组20只灌胃饮用水。2h后分组给药：对照组及模型组灌胃饮用水，川芎嗪50mg·kg^-1·d^-1；苯那普利1．8mg·kg^-1·d^-1。分别于4、8、12w末分别处死动物各6只，检测肾功能，肾脏病理，免疫组化观察FTC密度及VEGF表达。结果12w时模型组的血肌酐／体重水平明显升高（P〈0．01），病理表现为弥漫性小管间质损害和灶性纤维化；模型组4w后出现中、重度肾血管病变，FTC密度明显下降；肾小管VEGF表达水平早期代偿性增高，以后逐渐降低并与FTC密度下降一致。川芎嗪组、苯那普利组的肾功能及小管间质病变程度较模型组降低（P〈0．01）；血管病变程度轻，FTC密度明显高于模型组，VEGF表达水平低于模型组。结论马兜铃酸可引起大鼠肾功能减退和肾小管间质损害，使肾间质微血管发生缺血性病变，川芎嗪可改善上述病变程度，并与调节VEGF表达有关。

Objective To investigative the renal danage, renal imertitial rnicrovasculature and the expression of vascular endothelial growth factor （VEGF）in rats with aristolochic acid nephropathy, and the effects of Ligustrazine and Benazepril.Method 98 male wistar rats were divided into 4 groups randomly, the model group, Ligustrazine group, and Benazepril group were treated with Extracta of Caulis Aristolochiae Manshuriensis （aristolochic acid AA 20 mg·kg^-1·d^-1 intragastically, and the control group treated with potable water. 2hours later, the therapy group were treated with Ligustrazine 50 mg·kg^-1·d^-1 , or with Benazepill 1.8 mg·kg^-1·d^-1 ,the control and model group with equal volume of potable water respectively. At the end of 4th,8th, 12th week, the rats were sacrificed, the blood samples were collected for renal functiontests. Tubulo-interstitial injury, interstitial fibrosis, peri-tubular capillary（PTC） and expression of VEGF were observed by morphological and immunohistochemical analysis. Results The level of serum creatinin/bodyweight increased markedly in the model group at 12th week. There was significant tubular injury and interstitial fibrosis,and the PTC density decreased significantly after 4 weeks. The expression of tubular VEGF was compensatory up-regulated in early stagc, but down-regulated gradually. In the therapy groups, the renal function and the pathological changes were less, and the PTC density was higher than the model groups. The expression of VEGF was lower than model groups. Conclusions AA may induce impairment of renal function and progressive interstitial fibrosis, along with vascular injury and PTC loss, which being correlated to comparatively deficiency expression of VEGF; Ligustrazine could improve the renal function and PTC injury.