淫羊藿苷通过降低醛固酮水平减轻自发性高血压大鼠肾间质纤维化

Icariin attenuates renal interstitial fibrosis by reducing aldosterone in SHR

目的观察淫羊藿苷(icariin,ICA)对自发性高血压大鼠肾间质纤维化的干预作用,并探讨其机制。方法 14只13周龄的♂自发性高血压大鼠(SHR),随机分为模型组(n=7)和ICA组(n=7),同源正常的京都大鼠(WKY)作为对照组(n=7)。所有大鼠适应性饲养1周后,ICA组给予ICA40 mg·kg-1,ig,bid,至26周龄,模型组和对照组给予等量生理盐水。通过HE和Masson染色观察肾脏病理学变化;双抗体夹心法测定大鼠血浆醛固酮和Ⅲ型胶原含量;real time RT-PCR法检测肾脏组织中转化生长因子-β1(transforming growth factor-β1,TGF-β1)、Smad2、结缔组织生长因子(connective tissue growth factor,CTGF)、纤维连接蛋白(fibronectin,FN)mRNA的表达。结果与正常对照组比较,模型组肾脏结构较紊乱,肾小球系膜基质增多,肾小管间质纤维化明显;血浆醛固酮和Ⅲ型胶原含量增高(P<0.01);TGF-β1、Smad2、CTGF、FN mRNA的表达明显上调(P<0.01或P<0.05)。与模型组比较,ICA组肾脏结构有所改善,纤维化减轻;血浆醛固酮和Ⅲ型胶原含量降低(P<0.01或P<0.05);TGF-β1、Smad2、CTGF、FN mRNA的表达明显下调(P<0.01或P<0.05)。结论 ICA能改善自发性高血压大鼠肾间质纤维化,其机制可能与降低血浆醛固酮水平及下调TGF-β1和Smad2的表达有关。

Aim To investigate the effect of icariin （ ICA） on renal interstitial fibrosis in SHR and explore its mechanism. Methods Fourteen male SHR of 13-week-old were randomly divided into model group（ n=7 ） and ICA group （ n=7 ） , and WKY as control group （n=7）. One week after adaptive breeding,the rats in the ICA group were given ICA 40 mg＆#183;kg-1,ig,bid to 26-week-old. The other rats in the model group and control group were given the same amount of normal sa-line. Then, the morphological changes of the kidney were observed by HE and Masson staining,respective-ly. The contents of plasma aldosterone andⅢcollagen were measured by double antibody sandwich method. The mRNA expressions of TGF-β1 , Smad2 , CTGF and FN were examined by real time RT-PCR. Results Compared with the normal control group, the kidney structures of model group were disordered,the mesang-ial matrix and the tubular interstitial fibrosis were in-creased. The contents of plasma aldosterone and Ⅲcollagen were increased in model group （ P ＆lt;0. 01 ） . And the mRNA expressions of TGF-β1 , Smad2 , CTGF and FN in kidney tissues were up-regulated in model group（ P ＆lt;0. 01 or P ＆lt;0. 05 ） . Compared with the model group,the kidney structures were improved and the contents of plasma aldosterone and Ⅲ collagen were reduced, as well as the mRNA expressions of TGF-β1,Smad2,CTGF and FN in kidney tissues were down-regulated（P＆lt;0. 01 or P＆lt;0. 05）in ICA group. Conclusion ICA may have anti-renal interstitial fi-brosis effect on SHR,and the mechanism might be re-lated to the reduced plasma aldosterone levels and the down-regulated expression of TGF-β1 and Smad2 .