雷洛昔芬和阿伐他汀对大鼠动脉粥样硬化模型的干预效果研究

目的：研究雷洛昔芬和阿伐他汀对于老年去卵巢大鼠动脉粥样硬化过程中血管内皮功能的影响。方法：40只老年的雌性大鼠随机分为4组,对照组、雷洛昔芬组、阿伐他汀组和联合用药组,所有的大鼠均卵巢切除术并饲喂高脂饲料4周,造模结束后,对照组给予等量生理盐水,雷洛昔芬组给予3 mg/kg雷洛昔芬,阿伐他汀组给予30mg/kg阿伐他汀,联合用药组给予3 mg/kg雷洛昔芬＋30 mg/kg阿伐他汀。给药4周后,麻醉处死,免疫组化检测胸主动脉中MCP-1含量,Elisa法检测胸主动脉中ERα、ERβ、iNOS、eNOS、ET-1和TNF-α含量。结果：雷洛昔芬和阿伐他汀均对ERα不产生作用（P〉0.05）;ERβ三个给药组均优于对照组（P〈0.05）,阿伐他汀组和联合用药组之间无差异（P〉0.05）且均优于雷洛昔芬组（P〈0.05）;iNOS阿伐他汀组和联合用药组之间无差异（P〉0.05）且均优于对照组（P〈0.05）;eNOS对照组和雷洛昔芬组无差异（P〉0.05）,阿伐他汀组和联合用药组之间无差异（P〉0.05）且均优于对照组（P〈0.05）;ET-1不论单用或者联合使用雷洛昔芬和阿伐他汀组均优于对照组（P〈0.05）,联合用药组优于两药单独使用（P〈0.05）;TNF-α对照组、雷洛昔芬组之间无差别,阿伐他汀组和联合用药组优于对照组。MCP-1在对照组、阿伐他汀组和雷洛昔芬组之间无显著差异。联合用药组优于其他三组。结论：在老年去卵巢大鼠中,雷洛昔芬和阿伐他汀给药可显著改善血管内皮功能紊乱和降低炎症相关指标,这两个药物的联合治疗可以用于预防绝经后动脉粥样硬化的发展。

Study on Raloxifene and Atorvastatin in Intervention of Rat Atherosclerosis Model

Objective： To study the influence of the endothelial function by raloxifene and atorvastatin in elder ovariectomized rats atherosclerosis. Methods ： 40 old female rats were randomly divided into four groups ： control group, raloxifene group, atorvastatin group and combined treatment group. All of the rats were ovariectomied and fed high fat forage for 4 weeks. After that, the control group was given equivalent physiological saline; raloxifene group was given 3 mg/kg; raloxifene and atorvastatin group was given 30 mg/kg atorvastatin; combined treatment group was given 3 mg/kg, raloxifene ＋ 30 mg/kg atorvastatin. Taking medicine for 4 weeks, rats were given anesthesia and killed, immunohistochemically detecting the thoracic aorta MCP - 1. ELISA method was used to detect the thoracic aorta ER ot , ER 13 , iNOS, eNOS, ET-1 and TNF- et. Results ： Raloxifene and atorvastatin had no difference in ER ot （ P〉0.05 ）. For ER , three treatment groups were better than control group （ P〈0.05 ）. Atorvastatin and combined treatment group had no difference （ P〉0.05 ） and was better than raloxifene group （ P〈0.05 ）. For iNOS, atorvastatin and combined treatment group had no difference （ P〉0.05 ） and＇all were superior to the control （ P〈0.05 ）. For Enos, the control group and raloxifene group had no difference （P〉0.05）, atorvastatin and combined treatment group had no difference （ P〉0.05 ）and all were superior to the control group （ P〈0.05 ）. No matter using alone or in combination, for ET-1, raloxifene and atorvastatin were better than that in control group （/9〈0.05 ）, combined treatment group was better than the two drugs used alone （ P〈0.05 ）. In TNF- et , control group and raloxifene groups had no difference and atorvastatin group and combined treatment group they were better than control group. MCP - 1 in the control group, raloxifene and atorvastatin had no significant difference. Combined treatment group was better than the other three groups. Conclusion ： In the elder ovariectomized rats, raloxifene aod atorvastatin can significantly improve endothelial dysfunction and reduce inflammation related indexs. The two drugs combination therapy can be used to prevent postmenopausal atheroselerosis development.