目的:探讨补阳还五汤对同型半胱氨酸(homocysteine,Hcy)致动脉粥样硬化(AS)的保护作用与细胞间隙连接蛋白(connexin,Cx)的关系。方法:将32只雄性载脂蛋白E基因敲除(ApoE-/-)小鼠随机分为模型组、补阳还五汤低、中、高剂量组,以正常雄性C57BL/6J小鼠设正常对照组。模型组和治疗组采用Hcy ig造模,0.1 g.kg-1.d-1。造模同时,治疗组分别ig补阳还五汤(5,10,20 g.kg-1.d-1)。8周后观察和测量主动脉根部AS斑块面积、血管壁面积,检测主动脉组织活性氧(ROS)含量,p38MAPK,ERK,Cx37,Cx43蛋白表达变化。结果:模型组AS病变明显,主动脉组织中ROS含量(17.01±1.31)×105 RFU与正常对照组ROS含量(2.73±0.18)×105 RFU相比显著升高(P〈0.01);模型组与正常组比p38MAPK,ERK,Cx43蛋白表达明显增高,Cx37蛋白表达显著降低;不同剂量的补阳还五汤改善AS病变的同时显著降低血管组织中ROS含量,下调p38MAPK,ERK,Cx43的蛋白表达水平,提高Cx37蛋白的表达水平。结论:补阳还五汤可能通过拮抗有丝分裂激活蛋白激酶磷酸化水平,改善细胞间隙连接而抗Hcy所致动脉硬化的作用。
Objective:To study the possible link between preventing effect of Buyang Huanwu decoction(BHD) for atherosclerosis(AS) with connexins(Cx).Method:Thorty-two male ApoE-/-mice were randomly divided into four groups:model group and three dose groups of BHD(5,10,20 g·kg-1·d-1).C57BL/6J mice was used to set up a normal control group.AS model was established by intragastric administration of homocysteine(0.1 g·kg-1·d-1).Meanwhile,treatment groups were intragastric administrated with BHD(5,10,20 g·kg-1·d-1).Eight weeks later,the area of atherosclerotic plaques,blood vessel walls and the ratio between them were observed and measured.The aortic ROS content and the expression of MAPKp38,ERK,Cx37,Cx43 were determined.Result:Model group showed evident AS lesions differently to the three treatment groups.The model group ROS content was elevated(17.01±1.31) ×105 RFU,compared with that in control group(2.73±0.18)×105 RFU,showing significant difference(P 0.01).The MAPKp38,ERK,Cx43 protein expressions were significantly elevated,while Cx37 decreased in the models.Different doses of BHD could decrease ROS content,down-regulate MAPKp38,ERK,Cx43 protein expressions,and up-regulate Cx37 expression.Conclusion:BHD could prevent atherosclerosis induced by homocysteine via preventing AMPKs and regulating connexin expression.