冠脉宁口服液干预ApoE基因敲除小鼠动脉粥样硬化的实验研究

摘要

目的：探讨冠脉宁口服液对 ApoE基因敲除小鼠(ApoE /小鼠)动脉粥样硬化病变(AS)的影响及其机制。方法30只以 C57BL/6J为背景的10周龄 ApoE /小鼠,高脂饲料喂养12周后随机分为3组：模型组、冠脉宁组、复方丹参组,每组10只。冠脉宁组给予冠脉宁口服液20 g/(kg·d)灌服；复方丹参组给予复方丹参溶液3.5 g/(kg·d)灌服；模型组给予等量生理盐水灌服。另设10只相同背景和周龄的普通饲料喂养的C57BL/6J小鼠作为空白对照组。分别给药12周后小鼠摘除眼球采血,酶法检测血脂水平,ELISA方法检测血清中内脏脂肪素(visfatin)、白介素6(IL 6)水平。HE染色观察小鼠主动脉病理形态学变化。结果空白对照组主动脉未见动脉粥样硬化改变,模型组有较明显的主动脉内膜增厚及粥样斑块的形成。模型组血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL C)水平及血清中visfatin、IL 6的表达显著高于空白对照组,而高密度脂蛋白胆固醇(HDL C)水平则显著低于空白对照组(P<0.05)。与模型组比较,冠脉宁组、复方丹参组 TC、TG、LDL C水平及血清中 visfatin、IL 6水平显著降低(P<0.05),而HDL C水平显著升高(P<0.05),且病理损伤程度减轻。冠脉宁组与复方丹参组比较,血脂指标、visfatin、IL 6水平差异无统计学意义(P>0.05)。结论冠脉宁口服液可降低 ApoE /小鼠的血脂水平及血清中 visfatin、IL 6水平,具有一定的抗动脉粥样硬化作用,可能通过调节血脂代谢、降低炎症细胞因子水平达到抑制动脉粥样硬化进展、稳定动脉粥样硬化斑块的目的。%Objective To explore the effects and its mechanisms of Guanmaining oral liquid (GOL)on atherosclerosis(AS)in apoli-poprotein E gene knockout mice(ApoE / mice).Methods Total y 30 C57BL/6J genetic background ApoE / mice which were 10 weeks old were fed a high fat diet for 12 weeks until the formation of a mature atherosclerotic plaque.They were randomly divided into three groups:model group,GOL group,compound salvia miltiorrhiza group,10 mice in each group. Another 10 wild type normal C57BL/6J mice were used as the blank control group.They were administered for 12 weeks.Blood was extracted from the bulbus ocu-lis.The serum lipid contents were observed with enzyme method.visfatin and interleukin 6 (IL 6)level were detected by enzyme linked immunosorbent assay(ELISA).HE stain was used to observe aortic pathomorphological changes.Results The blank control group showed no distinctive changes of atherosclerosis,the model group had distinctive increase of aortic intima thickness and ather-osclerotic plaque formation.The model group also had high serum levels of total cholesterol(TC),triglyceride(TG)and low density li-poprotcin(LDL),as wel as high visfatin and IL 6 expression .However,high density lipoprotein(HDL)in the model group was lower than the blank control group(al P<0.05).Compared with the model group,the serum levels of TC,TG,LDL C were decreased.Vis-fatin and IL 6 expression were lowered(P<0.05),while HDL C was increased(P<0.05)in Guan maining group and compound salvia miltiorrhiza group,degree of pathological damage was reduced.There was no significant difference in above mentioned indi-cators between GOL group and compound salvia miltiorrhiza group(P>0.05).Conclusion GOL could decrease the serum levels and the expression of visfatin and IL 6 of ApoE / mice.It can inhibit the development of atherosclerosis by regulating serum lipids, suppressing inflammation factors,which is the possible mechanism of stabilizing the atherosclerotic plaque.