右归丸干预肾间质纤维化的作用机制研究

Effect of Yougui Pill on Rats with Renal Interstitial Fibrosis

目的探讨右归丸对腺嘌呤诱导的大鼠肾间质纤维化(renal interstitial fibrosis,RIF)的干预作用。方法取SD大鼠50只,随机分为空白对照组,模型组,右归丸低、中、高(2.25,4.50,9.00 g·kg^(-1))剂量组,每组10只。每天上午8点各组给予腺嘌呤(0.15 g·kg^(-1))灌胃制备RIF模型,空白对照组给予等量生理盐水,下午17点右归丸各组灌胃给予相应剂量的右归丸,给药体积均为10 m L·kg^(-1),空白对照组和模型组给予等量生理盐水,连续15 d。给药期间定期测定大鼠体质量,实验结束称取各组大鼠肾质量并计算肾指数,肾组织进行病理HE染色,测定血清肌酐(SCr)、尿素氮(BUN)水平,抗氧化指标超氧化物歧化酶(SOD)和丙二醛(MDA),炎性因子白介素-1β(IL-1β)和白介素-6(IL-6)。结果与空白对照组比较,模型组大鼠体质量显著降低(P<0.01),肾质量、肾指数显著增加(P<0.01),SCr、BUN水平显著增加(P<0.01),肾小管重度萎缩、坏死。炎细胞浸润、纤维结缔组织增生,SOD显著降低、MDA显著增加(P<0.05,P<0.01),炎性因子IL-1β和IL-6显著增加(P<0.05,P<0.01)。与模型组比较,右归丸组对大鼠体质量有一定的改善作用,差异无统计学意义(P>0.05);但可减轻大鼠肾质量、肾指数(P<0.01),显著降低SCr、BUN水平(P<0.05),对肾小管重度坏死萎缩、炎细胞浸润及纤维结缔组织增生均有不同程度的改善作用,有显著增加SOD、降低MDA的作用(P<0.05),能够显著降低炎性因子IL-1β和IL-6的水平(P<0.05,P<0.01)。结论右归丸对腺嘌呤诱导的RIF有明显的改善作用。

Objective To observe the effect of Yougui pill（YP）on renal interstitial fibrosis（RIF）induced by adenine in rats. Methods Fifty male SD rats were randomly divided into blank control group, model group and low-,medium-,and high-dose YP groups（in the dosage of 2.25,4.50,9.00 g·kg^（-1）,respectively）,10 rats in each group.Rats of the blank control group received saline,and rats of the other groups were given adenine（0.15 g·kg（-1））orally daily at 8：00 to induce renal interstitial fibrosis model. And at 17∶00,rats of the blank control group and model group were given saline,and YP groups were given different dosage of YP at 10 m L·kg^（-1） for 15 continuous days.During the administration,we regularly weighed the body weight of the rats. At the end of the experiment,kidney weight was detected and renal morphology was examined after HE staining. Meanwhile, we detected the serum creatinine（CR）and blood urea nitrogen（BUN）levels,observed antioxidant indices of superoxide dismutase（SOD）and malondialdehyde（MDA）activities,and examined the inflammatory cytokines interleukin-1β（IL-1β）and interleukin 6（IL-6）. Results Compared with the blank control group,the body weight of model group was significantly decreased（P〈0.01）,kidney weight and kidney index were increased obviously（P〈0.01）,Cr and BUN levels were increased significantly（P〈0.01）, renal tubular atrophy and necrosis, and inflammatory cell infiltration were severe, SOD activities were significantly decreased and MDA activities were increased（P〈0.01）,and inflammatory factor IL-1β and IL-6 were increased（P〈0.01）. Compared with the model group,YP groups could increase the body weight of rats,reduce rat kidney weight and renal index（P〈0.05,P〈0.01）,significantly decrease the Cr and BUN levels（P〈0.05）,and relieve renal tubular degeneration,necrosis and atrophy,inflammatory cell infiltration and fibrous connective tissue to various degrees. Meanwhile,SOD activities were increased and MDA activities were decreased（P〈0.05,P〈0.01）,and inflammatory factors IL-1β and IL-6 levels were also decreased in YP groups（P〈0.05,P〈0.01）. Conclusion YP can significantly improve the renal interstitial fibrosis induced by adenine.