冠心舒通胶囊含药血清对AGEs诱导大鼠血管平滑肌细胞增殖的影响

目的:探讨冠心舒通胶囊含药血清对晚期糖基化终产物(AGEs)诱导血管平滑肌细胞(VSMCs)增殖的影响及其可能机制。方法:分别以0.5g/kg、1g/kg、2g/kg剂量冠心舒通胶囊内容物对大鼠灌胃给药28d制备冠心舒通胶囊含药血清;以各剂量含药血清单独或联合体外制备的AGE-牛血清白蛋白(AGE-BSA)处理原代培养大鼠VSMCs,MTT法检测各处理组细胞增殖水平、RT-PCR检测细胞血小板源性生长因子-B(PDGF-B)mRNA表达水平、酶联免疫吸附法(ELISA)检测培养上清PDGF-B浓度。结果:40mg/L终浓度AGE-BSA显著增强VSMCs增殖水平(P<0.05),0.5g/kg、1g/kg、2g/kg剂量冠心舒通胶囊含药血清对正常VSMCs生长未见显著影响(P>0.05),但显著抑制AGE-BSA诱导的VSMCs增殖(P<0.05),作用具有明显的剂量依赖性。AGE-BSA诱导VSMCs PDGF-B表达与分泌显著增强(P<0.05),1g/kg、2g/kg剂量冠心舒通胶囊含药血清可有效抑制AGE-BSA这一作用(P<0.05),0.5g/kg剂量血清对AGE-BSA这一作用则未见明显影响(P>0.05)。结论:冠心舒通胶囊可剂量依赖性抑制AGEs诱导的VSMCs增殖,作用机制与抑制AGE诱导的PDGF-B表达与分泌有关。

Influence of Guanxin Shutong containing serum on vascular smooth muscle cells proliferation induced by advanced glycation end products

Objective: To investigate the influence of Guanxin Shutong containing serum on advanced glycation end products(AGEs) induced vascular smooth muscle cells(VSMCs) proliferation and its possible mechanism.Methods: Rats were randomly divided into low,medium and high dose Guanxin shutong groups,respectively administrated with 0.5 g/kg.d,1 g/kg.d and 2g/kg.d Guanxin Sutong intragastrically.After continuous administration for 28 days,rat’s sera were harvested for subsequent cells culture experiments.Cultured rat’s aortic VSMCs were treated with different dose Guanxin Shutong containing serum in combination with or without in vitro prepared AGE-bovine serum albumin(AGE-BSA),subsequently;cells proliferation was tested by MTT assay,platelet-derived growth factor-B(PDGF-B) mRNA level in the cells and protein concentration in supernatant were detected respectively by RT-PCR and ELISA.Results: Guanxin Shutong containing serum didn’t show influence on growth of normal VSMCs but dramatically inhibited AGE-BSA induced VSMCs proliferation in a dose dependent manner.AGE-BSA significantly increased PDGF-B mRNA transcription and protein autocrine in VSMCs,this action could be effectively inhibited by 1g/kg and 2g/kg dose Guanxin Shutong containing serum but not by 0.5g/kg dose Guanxin Shutong containing serum.Conclusion: Inhibiting AGEs induced VSMCs proliferation is involved in mechanism of atherosclerosis prevention effect of Guanxin Shutong,suppressing AGEs stimulated PDGF-B expression and autocrine in VSMCs may partially contribute to this inhibitory action.