糖肾方抑制TGF-β1/Smad3通路促进小鼠肾小管上皮细胞胆固醇流出  

Tangshen formula promotes cellular cholesterol efflux in HG-induced mTECs by suppression of TGF-β1/Smad3 pathway

作　　者：刘鹏 赵海玲[2] 申正日 王晨 王昀 邱新萍 李平[2] LIU Peng;ZHAO Hailing;SHEN Zhengri;WANG Chen;WANG Yun;QIU Xinping;LI Ping(Shunyi Hospital,Beijing Traditional Chinese Medicine Hospital,Beijing 101300,China;Beijing Key Lab for Immol/Lune-Mediated Inflammatory Diseases,Institute of Clinical Medical Science,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京中医医院顺义医院,北京101300 [2]中日友好医院临床医学研究所,免疫炎性疾病北京市重点实验室,北京100029

出　　处：《中国临床药理学与治疗学》2021年第1期1-9,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：北京市顺义区科技三项费项目(KS201938);国家自然科学基金青年项目(8190152536);国家自然科学基金国际(地区)合作与交流项目(81620108031);北京中医医院顺义医院自然基金项目(SYYJ-201802)。

摘　　要：目的:利用高糖诱导的小鼠肾小管上皮细胞(mouse tubular epithelial cells,mTECs)观察中药糖肾方颗粒及Smad3抑制剂SIS3对于TGF-β1/Smad3通路及细胞胆固醇流出通路的影响。方法:25 mmol/L高糖诱导mTECs细胞后,分别给予糖肾方及Smad3抑制剂SIS3干预,利用ELISA试剂盒检测细胞中脂质含量,利用Western blot和Real-time PCR检测细胞中TGF-β1/Smad3通路及过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptorγcoactivator 1α,PGC-1α)、肝脏X受体(liver X receptor,LXR)、ATP-结合盒转运蛋白A1(ABCA1)、ATP-结合盒转运蛋白G1(ABCG1)的表达。结果:糖肾方可以降低高糖诱导mTECs细胞中总胆固醇(total cholesterol,TC)、甘油三酸酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)含量,上调高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)含量(P<0.05);糖肾方及Smad3抑制剂SIS3可下调高糖诱导mTECs细胞中TGF-β1、Smad3、CollagenⅠ和Fibronectin的表达,上调PGC-1α、LXR、ABCA1、ABCG1的表达(P<0.05)。结论:糖肾方可通过抑制TGF-β1/Smad3信号通路促进细胞胆固醇流出,减轻肾损害。AIM:To observe the effect of Tangshen formula(TSF)treatment on TGF-β1/Smad3 pathway and cellular cholesterol efflux and explore its potential mechanism in HG-induced mouse tubular epithelial cells(mTECs).METHODS:After 25 mmol/L high glucose induced mTECs,TSF and Smad3 inhibitor SIS3 were given to intervene respectively.The lipid content in the cells was detected by ELISA kit;TGF-β1/Smad3 pathway and PGC-1α,LXR,ABCA1,ABCG1 were detected by Western blot and real-time PCR.RESULTS:TSF diminished the levels of TC,TG,LDL-C and increased the levels of HDL-C in HG-induced mTECs.Western blot and real-time PCR analysis showed that expression levels of TGF-β1,Smad3,CollagenⅠand Fibronectin were significantly downregulated in the HG-induced mTECs with TSF and SIS3 treatment.And PGC-1α,LXR,ABCA1,ABCG1 expression levels were significantly upregulated in the HG-induced mTECs with TSF and SIS3 treatment.CONCLUSION:TSF can promote the cellular cholesterol efflux in HG-induced mTECs vis suppression of TGF-β1/Smad3 pathway.

关 键 词：糖肾方 糖尿病肾病 TGF-β1/Smad3通路 胆固醇流出 Smad3抑制剂SIS3 

分 类 号：R965.2[医药卫生—药理学]