辣椒素通过抑制肾小管间质纤维化改善高盐诱导肾脏损害的作用  

Capsaicin improved high-salt induced renal injury by inhibiting renal tubulointerstitial fibrosis

作　　者：赵宇[1,2] 李浩[1,3] 商黔惠[1,3] 任思斯 刘婵[1] 刘娟[1] 祝之明 ZHAO Yu;LI Hao;SHANG Qian-hui;REN Si-si;LIU Chan;LIU Juan;ZHU Zhi-ming(Institute of Clinical Medicine of Zunyi Medical College l Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi Guizhou 563003, Chin)

机构地区：[1]遵义医学院附属医院临床医学研究所心血管病研究所高血压研究室,贵州遵义563003 [2]遵义医学院附属医院内分泌科 [3]遵义医学院附属医院心内科 [4]第三军医大学第三附属医院高血压内分泌科

出　　处：《中华高血压杂志》2018年第4期349-356,共8页Chinese Journal of Hypertension

基　　金：国家自然科学基金资助项目(81160041;81460077);贵州省国际科技合作计划[G字(2012)7038号];贵州省优秀科技教育人才省长专项基金项目[黔省专合字(2012)15号];贵州省科技厅联合基金项目[黔科合LH字(2015)7535号]

摘　　要：目的探讨辣椒素对高盐诱导肾小管间质纤维化(RIF)的作用和机制。方法雄性Wistar大鼠36只,随机分为普食组(n=12,0.5%正常盐饲料)、高盐组(n=12,4%高盐饲料)、辣椒素组(n=12,4%高盐+0.02%辣椒素饲料)。每4周用智能无创鼠尾动脉血压仪测大鼠尾动脉收缩压;24周测定血肌酐、24h尿蛋白、尿视黄醇结合蛋白和尿TH-糖蛋白;HE、Masson染色观察肾髓质形态及纤维化;免疫组化法及Western-blot法检测肾髓质区瞬时受体电位通道香草醛亚型1(TRPV1)、转化生长因子β_1(TGF-β_1)、p-Smad2/3、α平滑肌肌动蛋白(α-SMA)、波形蛋白、Ⅰ型胶原、Ⅲ型胶原蛋白表达。结果与普食组相比,高盐组大鼠血压升高[(138.9±6.8)比(107.8±7.6)mm Hg,P<0.05],RIF指数明显增高(23.55±2.23比11.30±1.26,P<0.05),24h尿蛋白、视黄醇结合蛋白明显增高,TH-糖蛋白降低;肾脏髓质区TRPV1表达降低,TGF-β_1、α-SMA、p-Smad2/3、波形蛋白、Ⅰ型胶原、Ⅲ型胶原蛋白表达增高。辣椒素干预后,大鼠尾动脉收缩压较高盐组明显降低[(119.5±8.3)比(138.9±6.8)mm Hg,P<0.05],RIF指数明显降低(15.65±1.72比23.55±2.23,P<0.05),24h尿蛋白、视黄醇结合蛋白降低,TH-糖蛋白排泄增高,肾髓质TRPV1表达明显增加,TGF-β_1、α-SMA、p-Smad2/3、波形蛋白、Ⅰ型胶原、Ⅲ型胶原蛋白表达显著降低(均P<0.05)。结论长期高盐摄入可诱导Wistar大鼠RIF,辣椒素可能通过激活TRPV1,抑制RIF,改善高盐诱导的高血压肾脏损伤。Objective To investigate the effect of capsaicin on high-salt induced renal tubulointerstitial fibrosis in Wistar rats and its possible mechanism. Methods Thirty-six male Wistar rats were randomly divided into three groups：normal diet group[n=12,regular salt diet（0.5% salt）],high salt diet group[n=12,high salt diet（4%salt）],and capsaicin group[n=12,high salt（4% salt）＋0.02% capsaicin diet]. Tail arterial systolic blood pressure was measured by intelligent noninvasive blood pressure monitor every 4 weeks. The serum creatinine,24-hour urinary protein,24-hour urinary retinol binding protein（URBP）and Tamm-Horsfall（TH）glycoprotein were measured at the 24 th week. The morphological changes of renal medulla were observed by HE staining,and renal tubulointerstitial fibrosis was observed by Masson staining. In addition,the protein expressions of transient receptor potential vanilloid 1（TRPV1）,transforming growth factor-β_1（TGF-β_1）,p-Smad2/3,α-smooth muscle actin（α-SMA）,vimentin,collagen typeⅠ（ColⅠ）and collagen typeⅢ（ColⅢ）in the renal medulla were measured by immunohistochemistry and Western blotting. Results Compared with the normal diet group,the blood pressure[（138.9±6.8）vs（107.8±7.6）mm Hg,P〈0.05],fibrosis index of renal interstitium（23.55±2.23 vs 11.30±1.26,P〈0.05）,24-hour urinary protein,24-hour URBP were significantly increased,while 24-hour urinary TH glycoprotein was decreased in the high salt group. The protein expressions of TRPV1 was lower,while expression of TGF-β1,p-Smad2/3,α-SMA,vimentin,ColⅠand ColⅢin the renal medulla were higher in the high salt group than those in the normal diet group. Compared with the high salt group,the blood pressure [（119.5±8.3）vs（138.9±6.8）mm Hg,P〈0.05],fibrosis index of renal interstitium（15.65±1.72 vs 23.55±2.23,P〈0.05）,24-hour urinary protein,24-hour URBP were decreased,while 24-hour urinary TH glycoprotein and the protein expression of TRPV1 was significantly increased,the prot

关 键 词：高盐 辣椒素 转化生长因子Β1 肾小管间质纤维化 肾脏纤维化 

分 类 号：R544.1[医药卫生—心血管疾病] R692[医药卫生—内科学]