三七改善慢性肾脏病大鼠肾脏纤维化的研究

Research on radix notoginseng for improving CKD rat renal fibrosis

目的探讨三七及引经药介导的三七通过调控转化生长因子-β(TGF-β)的表达改善慢性肾脏病(CKD)大鼠肾脏纤维化的作用。方法将雄性SD大鼠100只随机分为5组:正常组(NOR,n=20)、模型组(CKD,n=20)、三七组(RN,n=20)、三七肉桂组(RNC,n=20)、三七桔梗组(RNP,n=20)。除NOR组外均采用腺嘌呤灌胃方法建立CKD大鼠模型,建模后NOR组和CKD组予以同等体积生理盐水灌胃,RN、RNC、RNP组予以相应药物灌胃,连续4周。4周后处死各组大鼠取血清检测肾功能[肌酐(Scr)、尿素氮(BUN)],取肾脏组织做HE、Masson染色观察各组大鼠肾脏组织病理损伤程度,应用免疫组化法检测肾脏组织纤维连接蛋白(FN)、层黏连蛋白(LN)表达,用Westetn blot法检测肾脏组织转化生长因子-β(TGF-β)、α-平滑肌肌动蛋白(α-SMA)表达。结果与NOR组相比,模型组肾功能能减退,Scr、BUN显著升高(P<0.01),肾间质出现严重纤维化表现,胶原的沉积增多(P<0.05),肾脏组织TGF-β、α-SMA、FN、LN表达显著升高。与模型组相比,各治疗组肾功改善,Scr、BUN明显降低(P<0.01),肾间质纤维化程度降低,胶原的沉积减少(P<0.05),肾组织α-SMA、TGF-β、FN、LN表达有所回降。其中RNC组作用强于RN组和RNP组。结论三七及引经药介导的三七均能不同程度延缓腺嘌呤所致CKD大鼠肾间质纤维化的进程,其可能机制是降低TGF-β蛋白表达。

Objective To investigate the effects of notoginseng and guiding medicinals mediated notoginseng for improving the renal interstitial fibrosis in rats with chronic kidney disease（CKD）by regulating TGF-βsignaling pathway.Methods A total of100 male SD rats were randomly divided into five groups：normal group（NOR,n=20）,model group（CKD,n=20）,radix notoginseng group（RN,n=20）,radix notoginseng plus platycodi group（RNP）and radix notoginseng plus cinnamon group（RNC,n=20）.Except for the NOR group,the CKD rat model in other groups was established by adenine gavage.After modeling,the NOR group and CKD group were given the same volume of normal saline by gavage,while the group RN,RNP and RNC were given corresponding drugs by gavage,for 4weeks.After 4weeks,the rats in each group were sacrificed for collecting serum and detecting the renal function（serum Scr,BUN）,the renal tissues were taken for conducting HE and Masson staining.Then the renal tissue pathological damage severity was observed.The expressions of FN and LN in kidney tissue were detected by immunohistochemistry and the expressions of TGF-β,α-SMA were detected by Western blot method.Results Compared with the NOR group,the model group exhibited the renal dysfunction（P〈0.01）,renal interstitial severe fibrosis manifestation and increased collagen deposition（P〈0.05）,and the expression of kidney tissuesα-SMA（P〈0.01）,TGF-β（P〈0.01）,FN and LN were significantly increased.Compared with the model group,the renal function in various treatment groups was improved,Scr（P〈0.01）and BUN（P〈0.01）were significantly decreased,the renal interstitial fibrosis degree was reduced,collagen desposition was decreased（P〈0.05）,renal tissueα-SMA（P〈0.05）,TGF-β（P〈0.05）,FN and LN expression were reduced to some extent,in which the effect of RNC group was stronger than that of the RN group and RNP group.Conclusion Notoginseng and guiding medicinals mediated notoginseng can retard the progression of renal interstitial fibrosis caused by adenine in CKD rat in varying degrees,its mechanism maybe reduce the expression of TGF-βprotein.