绞股蓝皂苷对AGEs诱导下人肾小球系膜细胞中RAGE及转化生长因子-β_1表达的影响  

Effect of gypenosides on RAGE and TGF-β_1 expression in human mesangial cells induced by AGEs

作　　者：张秋艳[1] 唐灵[1] 王艳[1] 周康[1] 张慧云[1] 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)

机构地区：[1]桂林医学院附属医院老年内科,广西桂林541001

出　　处：《中国药理学通报》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)

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.

关 键 词：绞股蓝皂苷 糖尿病肾病 人肾小球系膜细胞 晚期糖基化终末产物 晚期糖基化终末产物受体 转化生长因子-β1 纤维化 

分 类 号：R284.1[医药卫生—中药学] R322.61[医药卫生—中医学]