淫羊藿苷对血管紧张素Ⅱ诱导肾纤维化的保护作用研究  

Protective effect of icariin on angiotensin Ⅱ induced renal fibrosis

作　　者：顾向晨[1] 张红利 程烨 王怡[1] 陈敏[1] GU Xiangchen;ZHANG Hongli;CHENG Ye;WANG Yi;CHEN Min(Division of Nephrology,Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院肾内科,上海200437

出　　处：《上海医学》2020年第10期611-617,共7页Shanghai Medical Journal

基　　金：上海市浦江人才计划(18PJD049);上海市进一步加快中医药事业发展三年行动计划(2014年-2016年)(ZY3-JSFC-2-2018)。

摘　　要：目的探讨淫羊藿苷是否具有抑制血管紧张素Ⅱ诱导的肾脏纤维化作用。方法选取雌性成年的Wistar大鼠并随机分为6组,建立去势后血管紧张素Ⅱ诱导大鼠肾纤维化模型。即假手术(Sham)组、假手术+血管紧张素Ⅱ(Sham+AngⅡ)组、假手术+血管紧张素Ⅱ+淫羊藿苷(Sham+AngⅡ+I)组、手术去势(OVX)组、手术去势+血管紧张素Ⅱ(OVX+AngⅡ)组、手术去势+血管紧张素Ⅱ+淫羊藿苷(OVX+AngⅡ+I)组,每组6只。4周后处理模型大鼠,检测各组大鼠的肾功能、雌激素水平表达变化和肾脏纤维化指标变化情况。取处于对数生长期的大鼠肾脏正常成纤维细胞株(NRK-49F),分为二甲基亚砜(DMSO)处理对照组、AngⅡ组和AngⅡ+I组3组,提取细胞总RNA,检测各组细胞纤维化相关基因表达情况。结果与Sham组相比,OVX组血清肌酐、尿素氮水平和尿微量白蛋白/肌酐(MA/Cr)值均轻度升高,但差异无统计学意义(P值均>0.05)。Sham+AngⅡ组和OVX+AngⅡ组血清肌酐、尿素氮和尿MA/Cr值分别较Sham组和OVX组显著升高(P值均<0.05)。Sham+AngⅡ+I组和OVX+AngⅡ+I组血清肌酐、尿素氮水平和尿MA/Cr值分别较Sham+AngⅡ组与OVX+AngⅡ组显著降低(P值均<0.05)。与Sham组比较,OVX组和OVX+AngⅡ组血清雌二醇(E2)水平均显著降低(P值均<0.05)。与OVX+AngⅡ组比较,OVX+AngⅡ+I组E2水平显著升高(P值均<0.05)。行去势手术的3组促卵泡素(FSH)水平均分别较未行去势手术的3组显著升高(P值均<0.05)。与Sham组比较,Sham+AngⅡ组肾间质纤维化面积、纤维化相关基因表达量均显著增加(P值均<0.05);与Sham+AngⅡ组比较,Sham+AngⅡ+I组肾间质纤维化面积、纤维化相关基因表达量均显著减少(P值均<0.05)。与OVX组比较,OVX+AngⅡ组肾间质纤维化面积、纤维化相关基因表达量均显著增加(P值均<0.05),而OVX+AngⅡ+I组肾间质纤维化面积、纤维化相关基因表达量均显著减少(P值均<0.05)。与DMSO组比较,细胞株AngObjective To identify whether icariin plays a protective role in angiotensinⅡinduced renal fibrosis.Methods Female adult Wistar rats were randomly divided into 6 groups(n=6):Sham group,Sham+angiotensinⅡgroup(Sham+AngⅡ),Sham+angiotensinⅡ+Ⅰcariin group(Sham+Ang II+Ⅰ),ovariectomized group(OVX),ovariectomized+angiotensinⅡ(OVX+AngⅡ),and ovariectomized+angiotensin ll+I cariin(OVX+Ang II+I).After ovariectomy,the rats were subcutaneously infused with angiotensinⅡfor four weeks.Then renal functions,hormone levels and fibrotic markers were measured.Normal rat kidney fibroblast cell lines(NRK-49F)in the logarithmic growth phase were divided into three groups:DMSO control group,angiotensinⅡgroup,angiotensinⅡ+icariin group.After extracting RNA from cells,the mRNA level of fibrotic maker genes was measured.Results As compared to sham group,serum creatinine,BUN and urinary Microal buminnuria/creatinine(MA/Cr)levels were slightly increased in OVX group;however,no significant difference was found(all P>0.05).Serum creatinine,BUN and urinary MA/Cr in sham+AngⅡgroup and OVX+AngⅡgroup were significantly higher than those in sham group and OVX group(all P<0.05).Serum creatinine,BUN and urinary MA/Cr in sham+AngⅡ+l group and OVX+AngⅡ+l group were significantly lower than those in sham+AngⅡgroup and OVX+Ang II group(all P<0.05).Estradiol level was significantly decreased in OVX group and OVX+AngⅡgroup as compared to sham group(both P<0.05).FSH expression in three ovariectomized groups was significantly upregulated as compared to three non-surgical groups(all P<0.05).Renal interstitial fibrotic area and the mRNA expression of fibrotic genes in sham+AngⅡgroup were significantly larger than those in sham group(both P<0.05).Renal interstitial fibrotic area and the mRNA expression of fibrotic genes in sham+AngⅡ+I group were significantly smaller than those in sham+AngⅡgroup(both P<0.05).Compared with OVX group,renal interstitial fibrosis significantly increased in OVX+Ang II group,while deceased in OV

关 键 词：淫羊藿甙 血管紧张素Ⅱ 肾纤维化 受体 雌激素 

分 类 号：R285.5[医药卫生—中药学]