基于TGF-β/Smad信号通路探讨蒙药大黄-3汤对慢性肾功能衰竭大鼠的肾脏保护作用  

The renal protective effect of Mongolian medicine rhubarb-3 decoction on rats with chronic renal failure based on TGF-β/Smad signaling pathway

作　　者：昂格力玛 宝苏日高 孟永梅 ANG-Ge-Li-ma;BAO Su-ri-gao;MENG Yong-mei(Mongolian Medicine Basic Experimental Center of Mongolian Medicine School,Inner Mongolia Medical University, Hohhot 010110,China)

机构地区：[1]内蒙古医科大学蒙医药学院蒙医基础实验中心,内蒙古呼和浩特010110

出　　处：《中国药理学通报》2022年第7期1099-1106,共8页Chinese Pharmacological Bulletin

基　　金：蒙药大黄-3汤的药效物质基础及开发应用研究(No RZ1900002243);自治区级人才匹配-321二层次项目(No DC1900003031)。

摘　　要：目的研究蒙药大黄-3汤对慢性肾功能衰竭(chronic renal failure,CRF)模型大鼠肾功能保护作用,并探讨其作用机制。方法SPF级SD大鼠随机分为正常组和造模组,造模组采用腺嘌呤灌胃法建立CRF模型。造模成功后随机分为模型,阳药,大黄-3汤低、中、高剂量组,并间隔给药共12周。生化检测CSF、BUN、Scr;HE和Masson染色观察肾组织病理变化;免疫组化检测肾组织PCNA和α-SMA的表达;RT-PCR检测肾组织CK18、Vimentin、TGF-β1、FN的mRNA表达;Western blot检测肾组织α-SMA、E-cadherin、PCNA、Smad2、Smad3的蛋白表达。TGF-β1诱导HMC异常增殖和HK-2间质转化并给予大黄-3汤含药血清治疗。CCK-8检测HMC增殖;RT-PCR法检测HK-2间质转化。结果与模型组比较,大黄-3汤治疗后,CRF大鼠BUN、Scr降低,肾组织纤维化相关蛋白及基因表达降低;大黄-3汤含药血清显著抑制HMC增殖及HK-2间质转化。结论大黄-3汤能改善CRF模型大鼠肾功能,其机制可能与抑制HMC增殖及HK-2间质转化的基础上可能通过调节TGF-β/Smad信号通路有关。Aim To study the protective effect of Mongolian medicine rhubarb-3 decoction on renal function of CRF model rats and explore its mechanism.Methods SD rats were randomly divided into normal group and model group.The model group was established by adenine gavage.After successful modeling,they were randomly divided into model,positive,rhubarb-3 decoction low,medium and high dose groups,which were administered at intervals for 12 weeks.The biochemical detection of CSF,BUN and Scr was performed.The pathological changes of renal tissues were observed by HE and Masson staining.The expression of PCNA andα-SMA in renal tissues was detected by immunohistochemistry.The mRNA expressions of CK18,Vimentin,TGF-β1 and FN in kidney tissues were detected by RT-PCR.The expressions ofα-SMA,E-cadherin,PCNA,Smad2,Smad3 protein in kidney tissue were detected by Western blot.TGF-β1 induced abnormal proliferation of HMC and interstitial transformation of HK-2,and at the same time,it was treated with serum containing rhubarb-3 decoction.The proliferation of HMC was detected by CCK-8.Interstitial transformation of HK-2 was detected by RT-PCR.Results Compared with the model group,BUN and Scr in CRF rats decreased,and the expression of fibrosis-related proteins and genes in renal tissue decreased after rhubarb-3 decoction treatment.The serum containing rhubarb-3 decoction significantly inhibited HMC proliferation and HK-2 interstitial transformation.Conclusions Rhubarb-3 Decoction can improve renal function in CRF model rats,and its mechanism may be related to inhibiting HMC proliferation and HK-2 interstitial transformation and probably regulating TGF-β/Smad signaling pathway.

关 键 词：蒙药 大黄-3汤 慢性肾功能衰竭 肾小球系膜细胞 肾小管上皮细胞 TGF-β/Smad通路 

分 类 号：R-332[医药卫生] R282.71R291.2R322.61R329.28R692.5