葛根素联合丹参酮ⅡA对糖尿病血管病变大鼠炎症相关因子的影响

Effect of Puerarin Combined with TanshinoneⅡA on Inflammatory Factors in DM Rats with Vascular Lesions

目的:观察葛根素联合丹参酮ⅡA对糖尿病血管病变大鼠的保护作用及其相关机制。方法:高脂饲料喂养大鼠给予尾静脉注射链脲佐菌素(STZ)制作糖尿病血管病变模型,将造模成功大鼠随机分为模型对照组、葛根素0.5 g/kg+丹参酮ⅡA1 g/kg组、葛根素0.25 g/kg+丹参酮ⅡA 0.5 g/kg组、葛根素0.05 g/kg+丹参酮ⅡA 0.1 g/kg组,丹参酮ⅡA 0.5 g/kg组,葛根素0.25 g/kg组,阳性对照(二甲双胍0.09 g/kg)组,连续给药70 d。观察药物干预后大鼠体重及一般情况;采用全自动生化分析仪检测大鼠血糖、血脂含量;采用ELISA法检测大鼠血清胰岛素(insulin,INS)、晚期糖基化终末产物(advanced glycation end products,AGEs)含量,主动脉匀浆AGEs、oxLDL、单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)、TNF-α含量;HE染色观察冠状动脉组织病理学改变;免疫组织化学染色观察主动脉血管细胞粘附分子-1(vascular cell adhesion molecule 1,VCAM-1)、细胞间粘附分子-1(intercellularadhesion molecule 1,ICAM-1)蛋白表达。结果:与正常对照组比较,模型组血糖、血脂、血清INS含量以及AGEs、主动脉匀浆AGEs、oxLDL、TNF-α和MCP-1含量均明显升高,主动脉组织ICAM-1和VCAM-1蛋白表达明显增强;与模型组比较,葛根素0.5 g/kg联合丹参酮ⅡA 1 g/kg组可明显降低血糖及血脂(CHOL、LDL-C)含量,降低血清胰岛素含量,降低主动脉匀浆AGEs、oxLDL、MCP-1、TNF-α含量,减轻冠状动脉组织病变,下调主动脉组织VCAM-1、ICAM-1蛋白表达,配伍使用效果好于单药。结论:葛根素联合丹参酮ⅡA能减轻糖尿病大鼠血管病变,其机制可能与抑制炎症反应有关。

Objective:To observe the protecting effect and mechanism of Puerarin combined with TanshinoneⅡA on DM(diabetes mellitus)with vascular lesions in rats.Methods:The rats(fed with high fat diet)were injected intravenously STZ to establish diabetes model with vascular lesions.Model rats were randomly divided into the model control group,the combination of Puerarin and TanshinoneⅡA(0.5 g/kg+1 g/kg)group,the combination of Puerarin and TanshinoneⅡA(0.25 g/kg+0.5 g/kg)group,the combination of Puerarin and TanshinoneⅡA(0.05 g/kg+0.1 g/kg)group,TanshinoneⅡA(0.5 g/kg)group,Puerarin(0.25 g/kg)group and the positive control(Metformin,0.09 g/kg)group.Rats in each group were administered respectively for 70 days.After administration,the general condition and body weights of rats were observed.The contents of blood glucose and blood lipids were determined by Automatic Biochemical Analyzer.The contents of insulin and AGEs in serum,as well as the contents of AGEs,oxLDL,MCP-1 and TNF-αin aorta homogenate were detected by ELISA.Pathological changes of coronary tissues were observed by HE staining.The protein expressions of VCAM-1 and ICAM-1 of aorta were observed by immunohistochemistry.Results:Compared with the control group,levels of blood glucose and blood lipids,the contents of insulin in serum,AGEs,oxLDL,MCP-1 and TNF-αin aorta homogenate were significantly increased in the model group.The protein expressions of VCAM-1 and ICAM-1 of aorta were significantly increased.Compared with the model group,levels of blood glucose and blood lipids were decreased,the contents of serum insulin,AGEs,oxLDL,MCP-1 and TNF-αin aorta homogenate were decreased.The coronary lesions were relieved,and the protein expressions of VCAM-1 and ICAM-1 of aorta were reduced.Puerarin combined with TanshinoneⅡA showed better results than single administration.Conclusion:Combination of Puerarin and TanshinoneⅡA can relieve vascular lesions of DM rats.The mechanisms may be related to the inhibition of inflammatory response.