瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的：观察他汀类调脂药物瑞舒伐他汀（Rosuvastatin）对2型糖尿病（type2diabetesmellitus,T2DM）大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法：将45只雄性SD大鼠随机分为正常对照组（NC组）、2型糖尿病组（DM组）、2型糖尿病瑞舒伐他汀治疗组（DR组）,每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/（kg.d）灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）水平与稳态血糖（BG）、稳态胰岛素（PGI）浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40（clusterofdifferentiation 40,CD40）及基质金属蛋白酶-2（MMP-2）、激活蛋白-1（activator protein-1,AP-1）的表达水平。结果：DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高（F=33.71~426.05,q=5.26~40.82,P〈0.01）,但2组间各指标比较差异无显著性（P〉0.05）。DR组CD40、MMP-2、AP-1表达水平和浸润的单核细胞数明显低于DM组（F=36.86~716.82,q=8.59~37.86,P〈0.05）,DR组主动脉内皮损伤明显轻于DM组。结论：瑞舒伐他汀能抑制CD40、MMP-2、AP-1表达和单核细胞浸润,防止早期AS形成。

Inhibition of Early Atherogenesis by Rosuvastatin in Male Ratswith Diabetes Mellitus

Objective：To investigate the effects of rosuvastatin on early atherogenesis in male rats with type 2 Diabetes Mellitus,and to explore the mechanism of them.Methods：Forty-five male SD rats were randomly and equally divided into three groups：control group（NC group）,DM group and rosuvastatin group（DR group）.High fat and high glucose diet were given to establish the DM rat model.The rats in DM and DR group were fed with high-glucose and high fat diet for one month,and were injected with streptozotocin（25mg/kg） intraperitoneally.The rats in NC group were fed with full diet,and were injected with citrate buffer.After that,DR group was given rosuvastatin 5mg/（kg·d）,while NC group and DM group were given normal saline.All the medicine was given by intragastric administration for the three groups.sixteen weeks,to measure the TC,TG,LDL-C,BG and PGI.Immunohistochemistry was used to analyze the expressions of CD40,MMP-2 and AP-1 in aortic wall.Results：The levels of TC,TG,LDL-C and BG in DM and DR groups were markedly higher than that of NC group（F=33.71～426.05,q=5.26～40.82,P〈0.01）,but the differences between DM group and DR group were not significant（P〉0.05）.The CD40,MMP-2 and AP-1 expression level in DR group and the monocytes infilitrating into the intima of the aorta was significantly lower than that of DM（F=36.86～716.82,q=8.59～37.86,P〈0.05）.The endothelial damage of the aorta in rosuvastatin groups was less severe than that in DM group.Conclusion：Rosuvastatin can prevent early atherogenesis by inhibiting the CD40,MMP-2,AP-1expression and alleviating the monocytes infilitrating into the arterial wall.