摘要
目的观察绞股蓝皂苷(gypenosides,GP)对晚期糖基化终末产物(advanced glycation endproducts,AGEs)诱导下人肾小球系膜细胞(human mesangial cells,HMCs)中晚期糖基化终末产物受体(RAGE)及转化生长因子-β_1(TGF-β1)表达的影响。方法将体外培养的(体积分数为0.15的FBS的DMEM低糖培养液)人肾小球系膜细胞(HMCs)分为4组:正常组、模型组、GP组、阳性对照组。除正常组外,其余组均再给予200 mg·L^(-1)AGEs刺激。此外,GP组中加入不同浓度GP(25、75、175 mg·L^(-1))进行干预,阳性对照组中加入氨基胍盐酸盐(10^(-1)mmol·L^(-1))。应用Western blot技术检测各实验组中RAGE和TGF-β_1蛋白的表达;RT-PCR技术检测各实验组中RAGE和TGF-β_1 mRNA的表达。结果模型组AGEs诱导下HMCs中RAGE、TGF-β1蛋白及mRNA表达水平明显高于正常组(P<0.01);与模型组比较,GP组中GP可明显下调HMCs中RAGE、TGF-β_1蛋白及mRNA的表达,且呈浓度依赖性(P<0.01)。结论 GP可降低AGEs诱导下HMCs中RAGE的表达,阻断AGEs-RAGE信号通路,并下调下游因子TGF-β_1的表达,进而延缓糖尿病肾病纤维化进程。
Aim To observe the effect of gypenosides( GP) on the expression of receptor for advanced gly-cated endproducts( RAGE) and transforming growth factor-β_1( TGF-β_1) in human mesangial cells( HMCs)induced by AGEs. Methods HMCs were cultured in DMEM of low glucose containing 15% fetal bovine serum in vitro,which were divided into four groups: the normal group,model group,GP group and positive control group. In addition to the normal group,the other groups were stimulated by AGEs( 200 mg ·L^(-1)); furthermore,GP group was intervened with different concentrations( 25,75,175 mg · L^(-1)) of GP,while control group was given 10 mmol·L^(-1)of aminoguanidine hydrochloride. The expression of RAGE and TGF-β_1protein of each group was detected by Western blot; the expression of RAGE and TGF-β_1mRNA of each group was detected by RT-PCR. Re-sults The expression of RAGE,TGF-β_1protein and mRNA in HMCs induced by AGEs in the model group was significantly higher than that of the normal group( P 0. 01); compared with the positive control group( P 0. 01),GP could obviously reduce the expression of RAGE,TGF-β_1protein and mRNA in a dose-dependent manner. Conclusion GP can reduce the expression of RAGE in HMCs induced by AGEs,block AGEs-RAGE signaling pathway and decrease the expression of the downstream factor TGF-β_1,therefore,it plays the role in the resistance of rennal fibrosis in DN.
作者
张秋艳
唐灵
王艳
周康
张慧云
ZHANG Qiu-yan TANG Ling WANG Yan ZHOU Kang ZHANG Hui-yun(Dept of Geriatrics,the Affiliated Hospital of Guilin Medical University, Guilin Guangxi 541001 ,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2016年第9期1301-1306,共6页
Chinese Pharmacological Bulletin
基金
广西自然科学基金资助项目(No 2013GXNSFAA019197)
广西壮族自治区卫计委项目(No Z2016387)
桂林市科学研究与技术开发计划项目(No 20120121-1-1)