虫草益肾方对肾纤维化大鼠Hippo信号通路表达的影响  

Effect of Chongcao Yishen Formula on Hippo Signaling Pathway Expression in Rats with Renal Fibrosis

作　　者：苑伯菲 宋立群[1,2] 代丽娟[2] 于珊珊[1] 贠捷[1,2] Yuan Bofei;Song Liqun;Dai Lijuan;Yu Shanshan;Yun Jie(Heilongjiang University of Chinese Medicine,Heilongjiang,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040

出　　处：《中国中医急症》2021年第7期1134-1138,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学青年基金项目(81804088);国家中医药管理局国家中医临床研究基地业务建设科研专项课题任务书(JDZX2015192);黑龙江省普通本科高等学校青年创新人才培养计划(UPYSCT-2018222);黑龙江省政府博士后资助经费(LBH-Z15210);黑龙江中医药大学博士创新基金(2015bs01)。

摘　　要：目的研究虫草益肾方对单侧输尿管梗阻(UUO)模型大鼠的治疗效果,并探讨其分子机制。方法将40只SD大鼠随机分为假手术组、模型组、咪达普利组及虫草益肾方组,每组10只。其中,模型组、咪达普利组和虫草益肾方组采用UUO法制备肾间质纤维化(RIF)模型。每日分别灌服生理盐水、咪达普利水溶液及虫草益肾方水煎液,持续灌胃14 d后采集梗阻侧肾脏组织,检测血清中肌酐、尿素氮含量。取梗阻侧肾脏组织,Masson染色后观察肾脏组织纤维化程度,并用Western blotting法检测各组大鼠p-YAP、YAP、p-Mst1、Mst1、pLats1、Lats1及α-SMA、E-cadherin蛋白在梗阻侧肾脏组织中的表达。结果与假手术组相比,模型组大鼠血清肌酐、尿素氮水平上升,肾组织的肾间质纤维化程度明显升高,p-MST1、p-LATS1、p-YAP蛋白表达下调,MST1、LATS1、YAP蛋白表达基本不变,α-SMA蛋白表达上调,E-cadherin蛋白表达下调。与模型组比较,咪达普利组与虫草益肾方组血肌酐、尿素氮水平降低,肾组织纤维化面积减少,p-MST1、p-LATS1、p-YAP蛋白表达上调,MST1、LATS1、YAP蛋白表达基本不变,α-SMA蛋白表达下调,E-cadherin蛋白表达上调。结论虫草益肾方能保护UUO大鼠肾功能,其机制可能与调控Hippo信号通路中核心蛋白YAP、Mst1、Lats1蛋白磷酸化表达程度,从而抑制UUO大鼠肾小管上皮细胞间充质转分化,延缓RIF相关。Objective:To study the effect of Chongcao Yishen Formula(CCYSF)on unilateral ureteral obstruction(UUO)in rats and to explore the molecular mechanism.Methods:A total of 40 Sprague Dawley rats were randomly divided into sham operation group,model group,imidapril group and CCYSF group,with 10 rats in each group.Among them,the model group,imidapril group,and the CCYSF group made renal interstitial fibrosis(RIF)model by UUO method.Normal saline,imidapril aqueous solution and water decoction of CCYSF were administered daily.Serum and obstructed kidney tissues were collected after 14 days of continuous gavage,and the contents of creatinine and urea nitrogen in serum were detected.After Masson staining,the fibrosis degree of renal tissue was observed,and the expressions of p-YAP,YAP,p-Mst1,Mst1,p-Lats1,Lats1,α-SMA,E-Cadherin proteins in the obstructed renal tissue of rats in each group were detected by Western blotting.Results:Compared with the sham group,serum creatinine and urea nitrogen levels in the model group were increased,the degree of renal interstimal fibrosis was significantly increased,the protein expressions of p-MST1,p-LATS1 and p-YAP were down-regulated,the protein expressions of MST1,LATS1 and YAP were basically unchanged,the protein expression ofα-SMA was up-regulated,and the protein expression of E-cadherin was down-regulated.Compared with the model group,serum creatinine and urea nitrogen levels were decreased in the imidapril group and the CCYSF group,and the fibrosis area of renal tissue was reduced.The protein expressions of p-MST1,p-LATS1 and p-YAP were up-regulated,the protein expressions of MST1,LATS1 and YAP were basically unchanged,the protein expressions ofα-SMA were down-regulated,and the protein expression of E-cadherin was up-regulated.Conclusion:CCYSF can protect renal function in UUO rats,and its mechanism may be related to regulating the phosphorylation level of core proteins YAP,Mst1 and Lats1 in Hippo signaling pathway,thereby inhibiting the mesenchymal transdifferentiation of renal

关 键 词：单侧输尿管梗阻 肾间质纤维化 虫草益肾方 Hippo信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]