甘草酸对大鼠慢性马兜铃酸肾损害的保护作用及其机制研究

目的：探讨甘草酸对马兜铃酸肾病（AAN）大鼠肾损害及纤维化的保护作用及其机制。方法：雄性Wistar大鼠98只随机分为4组：对照组20只灌胃等体积饮用水，模型组、甘草酸组、泼尼松组每组26只，均按马兜铃酸（AA）20mg·kg^-1·d^-1灌胃关木通浸膏；2h后治疗组给予：甘草酸25mg·kg^-l·d^-1，泼尼松3.15mg·kg^-l·d^-1，对照组、模型组灌胃饮用水。分别于第4、8、12周处死动物，取肾组织行HE、PAS、Masson染色，病理学观察分析肾小管损伤和间质纤维化程度，免疫组化分析PCNA、VEGF、TGF-βl蛋白表达。结果：模型组肾小管损伤分值增高，纤维化程度严重，治疗组肾小管损害和纤维化程度均减轻（甘草酸组15，94％、泼尼松组12，49％）。模型组4周时PCNA、TGF-β1、VEGF水平显著升高，随着时间延长PCNA、VEGF表达逐渐下降，TGF-βl则呈持续阳性高表达；治疗组同期PCNA阳性表达水平较模型组高，VEGF、TGF-β1表达水平较模型组下降。结论：甘草酸对关木通致大鼠马兜铃酸肾损害和纤维化有一定保护作用，其机制可能与提高肾小管上皮的损伤修复能力，调节VEGF、TGF-β1的蛋白表达水平有关。

The Effects and Mechanism of Diammonium Glycyrrihizinate on Rat's Aristolochic Acid Induced Nephropathy

Objective： To investigate the therapeutic effects and its mechanism of Diammonium glyeyrrihizinate（DG） on nephropathy rats induced by aristoloehie acid, Methods： Ninety - eight male Wistar rats were divided into 4 groups randomly. The test group was divided into model group,DG group,and Prednisone group. Every group was treated intragastically with Extraeta of Aristoloehiae Manshuriensis Kom （aristoloehie acid. AA 20mg·kg^-l·d^-1） ; the control group had 20 rats whieh with equal volume of potable water. 2 h later, the ~ group was treated with 25mg·kg^-l·d^-1, the Prednisone group with Prednisone 3.15 mg·kg^-l·d^-1,and the control and model group with equal volume of potable water respectively. At the end of the 4^th,8^th, 12^th week, the rats were sacrificed and the renal tissues tubular injury and interstitial fibrosis on pathological section was semi - quantitatively determined. The protein expressions of proliferate cell nuelear antigen（PCNA）, vaseular endothelial growth factor（VEGF）, trans- forming growth factor-βl （TGF -βl） in the renal biopsy specimens were semi - quantitatively determined with immunohistoehemieal staining. Results：The model group showed severe tubular injury and interstitial fibrosis, the expression of PCNA, TGF- 31, VEGF were up- regulated markedly at 4th weeks. The PCNA, VEGF down - regulated gradually, but the TGF -βl were kept in high level as time going on. After intervention with DG or Prednisone, the tubular injury and fibrosis were improved significantly. The protein expression of PCNA was decreased gradually at 8^th, 12^th week, but was kept 1 time higher than that in the model group; and the TGF-βl, VEGF were significantly inhibited. Conclusion： DG could improve renal tubular damage and interstitial fibrosis in Acanthi, whieh might be related with promoting renal tubular proliferation, regulating the expression of TGF-βl and VEGF.