补阳还五汤抗动脉粥样硬化与间隙连接蛋白关系的研究

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。

Anti-atherosclerosis Effect of Buyang Huanwu Decoction Relates with Connexins

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.