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目的:探究补阳还五汤加味对动脉粥样硬化(AS)形成的预防及机制研究。方法:将30只雄性载脂蛋白E基因敲除小鼠(Apo E-/-小鼠)随机分为Apo E-/-小鼠组、模型组、补阳还五汤加味组和辛伐他汀组,另以正常雄性C57BL/6J小鼠设组。模型组、补阳还五汤加味组和辛伐他汀组采用高脂饮食造模。第4周后,补阳还五汤加味组和辛伐他汀组分别灌以补阳还五汤20 g·kg~(-1)+水蛭粉0.46 g·kg~(-1),辛伐他汀3 mg·kg~(-1)。第9周后,检测血清总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)值,取动物主动脉根部经苏木素-伊红(HE)常规染色后观察组织形态变化并测量纤维帽厚度和内-中膜厚度、检测主动脉p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节激酶5(ERK5)蛋白表达变化。结果:血脂水平,与C57BL/6J小鼠正常组比较,Apo E-/-小鼠组和模型组TC,TG,LDL-C均升高且HDL-C均降低(P<0.01);与模型组比较,补阳还五汤加味组与辛伐他汀组均能降低Apo E-/-小鼠TC,TG,LDL-C水平,同时升高HDL-C(P<0.05,P<0.01)。HE染色,C57BL/6J小鼠正常组主动脉管壁无斑块形成,Apo E-/-小鼠组管壁有极少斑块形成,内-中膜略有增厚。模型组斑块形成明显,内-中膜明显增厚。补阳还五汤加味组与辛伐他汀组较模型组斑块减少,内-中膜厚度减少。蛋白表达,与C57BL/6J小鼠正常组比较,模型组主动脉组织中p38MAPK的蛋白表达量增多(P<0.01),ERK5的蛋白表达量减少(P<0.01);与模型组比较,补阳还五汤加味组和辛伐他汀组均能降低p38MAPK蛋白的表达量(P<0.01),增加组织中ERK5蛋白的表达(P<0.01)。结论:补阳还五汤加味与辛伐他汀均有预防AS的作用。补阳还五汤加味预防AS发生的机制可能与干预MAPK信号通路中的p38MAPK,ERK5途径有关。
Objective: To investigate the prevention and mechanism of Buyang Huanwu Decoction on the formation of atherosclerosis (AS). Methods: Thirty male ApoE - / - mice were randomly divided into three groups: Apo E - / - mice, model group, BYHWD modified group and simvastatin Group, another set of normal male C57BL / 6J mice. Model group, Buyang Huanwu Decoction group and Simvastatin group with high-fat diet modeling. After 4 weeks, Buyang Huanwu Decoction group and Simvastatin group were respectively treated with 20g · kg -1 of Bu Yang Huanwu Decoction, 0.46 g · kg -1 of Leech Powder, 3 mg · kg -1. After 9 weeks, serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL- - Eosin (HE) routine staining and histological changes were observed and the thickness of the fibrous cap and the thickness of the intima - media were measured to detect the expression of p38 mitogen - activated protein kinase (p38MAPK) and extracellular signal - regulated kinase 5 (ERK5) in the aorta Variety. Results: Compared with the normal group, the level of TC, TG, LDL-C and the HDL-C of Apo E - / - mice and model group were significantly lower than those of the normal group (P <0.01) Compared with the control group, BYHWD modified group and Simvastatin group could lower the level of TC, TG and LDL-C in Apo E - / - mice and HDL-C at the same time (P <0.05, P <0.01). In HE staining, there was no plaque formation in the aortic wall of C57BL / 6J mice. Apo E - / - mice had minimal plaque on the wall and a slight thickening of the intima - media. The model group plaque formation, significantly increased in the medial - tunica media. Buyang Huanwu Decoction group and Simvastatin group than the model group plaque reduction, intima-media thickness decreased. Compared with the normal control group, the protein expression of p38MAPK in the aortic tissue increased (P <0.01) and the protein expression of ERK5 decreased (P <0.01) in C57BL / 6J mice. Compared with the model group, Both Huanwu decoction group and simvastatin group could reduce the expression of p38MAPK protein (P <0.01) and increase the expression of ERK5 protein (P <0.01). Conclusion: Buyang Huanwu Decoction and simvastatin have the effect of preventing AS. The mechanism of Buyang Huanwu Decoction in preventing and treating AS may be related to the intervention of p38MAPK and ERK5 in MAPK signaling pathway.