辣椒素对高盐诱导大鼠肾小球损害及转化生长因子β_1/Smads通路的影响  

The effect of capsaicin on high-salt-induced glomerular damage and transforming growth factor-β_1/Smads pathway in rats

作　　者：赵宇[1,2] 刘燕 商黔惠[1,3] 李浩[1,3] 任思斯[1,3] 刘婵 刘娟[1] 祝之明[5] ZHAO Yu;LIU Yan;SHANG Qian-hui;LI Hao;REN Si-si;LIU Chan;LIU Juan;ZHU Zhi-ming(Institute of Clinical Medicine of Zunyi Medical College Department of Cardiology,Affiliated Hospital of Zunyi Medical College,Zunyi Guizhou 563003,China)

机构地区：[1]遵义医学院附属医院临床医学研究所,贵州遵义563003 [2]遵义医学院附属医院内分泌科,贵州遵义563003 [3]遵义医学院附属医院心内科,贵州遵义563003 [4]清华大学附属垂杨柳医院 [5]陆军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9期837-844,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：目的探讨膳食辣椒素对高盐诱导肾小球损害的作用和机制。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)。用智能无创鼠尾动脉血压仪监测尾动脉压1次/4周;生化方法测定24h尿微量白蛋白、血尿肌酐;HE、Masson染色观察肾小球形态及胶原纤维;real-time聚合酶链反应法检测肾脏皮质区转化生长因子β1(TGF-β1)、Smad2、Smad3、Smad7的mRNA表达,Western-blot法检测皮质区瞬时受体电位通道香草醛亚型1(TRPV1)、TGF-β1、磷酸化Smad2/3(p-Smad2/3)、Smad7、Ⅰ型胶原的蛋白表达。结果与普食组相比,高盐组的大鼠颈动脉收缩压升高[(145.8±5.8)比(118.1±8.3)mm Hg,P<0.05],肾小球纤维化指数明显增高(23.2±2.4比13.6±1.1,P<0.05),24h尿微量白蛋白明显增高,肌酐清除率(Ccr)降低;肾脏皮质区TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达升高,Ⅰ型胶原蛋白表达增高、TRPV1蛋白表达降低。辣椒素干预后,大鼠颈动脉收缩压较高盐组明显降低[(125.5±6.8)比(145.8±5.8)mm Hg,P<0.05],肾小球纤维化指数明显降低(16.5±1.4比23.2±2.4,P<0.05),24hMAU明显降低,TRPV1蛋白表达增高,Ⅰ型胶原蛋白表达下降,上述TGF-β1/Smads通路各基因和蛋白表达也显著降低(均P<0.05)。结论辣椒素能改善高盐诱导肾小球损害,其机制可能与激活TRPV1、抑制TGF-β1/Smads通路有关。Objective To investigate the protective effects of dietary capsaicin on high-salt-induced progression of glomerular damage in Wistar rats. Methods Thirty-six male Wistar rats were randomly divided into three groups： normal diet group [n= 12, regular salt diet（0.5% ）], high salt diet group [n= 12, high salt diet（4%）], and high salt diet plus capsaicin group [n= 12, high salt diet（4 % ） with 0.02 % capsaicin inside]. Tail artery blood pressure was determined by intelligent noninvasive blood pressure monitor-mouse instrument every 4 weeks. The urinary microalbumin and 24-hour ereatinine were measured by biochemical methods. Glomerular sclerosis was observed by HE staining, and renal fibrosis was observed by Masson staining. In addition, the mRNA expression of transforming growth factor-β1 （TGF-β1）, Smad2, Smad3 and Smad7 were evaluated by real-time polymerase chain reaction （PCR） and the protein expression of transient receptor potential vanilloid 1 （TRPV1）, TGF-β1, p-Smad2/3 and Smad7 were observed by immunochemistry and quantitated by Western-blot analyses in renal cortex. Results Compared with the normal diet group, the blood pressure [-（145.8±5.8） vs （118.1±8.3）mm Hg, P〈0.05], fibrosis index of the glomerular （23.2±2.4 vs 13.6±1.1, P〈0.05） and the urinary microalbumin were increased in high salt group, creatinine clearance rate was decreased, the mRNA and protein expressions of TGF-β1 , Smad2, Smad3 and Smad7 were increased. After the intervention of capsaicin, the blood pressure [-（125.5± 6.8） vs （145.8±5.8）ram Hg, P〈0. 05], fibrosis index of the glomerular （16.5±1.4 vs 23.2±2.4, P〈0.05） and the urinary mi eroalbumin and expression of collagen type I were much lower than the high salt group, the gene and protein expression mentioned were also significantly reduced while TRPV1 was increased （all P〈0.05）. Conclusion High blood pressure and glomerular damage may be induced by long-term high salt diet in Wistar rats, capsaicin may reduce gl

关 键 词：高盐 辣椒素 转化生长因子β1/Smads 肾小球损害 

分 类 号：R692[医药卫生—泌尿科学]