辛伐他汀和二甲双胍对动脉粥样硬化大鼠动脉构型及CD40/CD40L表达的影响

Effect of Simvastatin and Metformin on Aortic Configurational Changes and CD40/CD40L Expression in Atherosclerosis Rats

目的探讨辛伐他汀和二甲双胍对动脉粥样硬化(AS)大鼠血脂、动脉病理及构型变化、血清及动脉组织CD40L水平的影响及可能机制。方法成年SD雄性大鼠50只,随机分为N组(对照组)、SF组(高盐高脂组)、ST组(辛伐他汀组)、MT组(二甲双胍组)、ST+MT组(辛伐他汀+二甲双胍组),每组10只,N组用标准饲料饲养,其他组用高盐高脂饲料饲养。喂养16周后,检测各组血脂、动脉组织病理及构型、血清及动脉组织CD40L水平。结果 (1)血脂:SF组总胆固醇、三酰甘油明显高于N组(P<0.01),ST组与N组比较差异无统计学意义(P>0.05);MT组、ST+MT组明显低于N组(P<0.01)。(2)动脉组织病理:N组无异常;ST组、MT组、ST+MT组均有不同程度的中膜增厚,未形成典型AS斑块;SF组可见典型AS斑块。(3)主动脉构型变化:各组中膜层厚度均较N组增厚,增厚程度依次为SF>MT>ST>ST+MT。LA/TVA比值:SF组较N组、ST组、MT组及ST+MT组均减小(P<0.01),ST组与MT组、ST+MT组与N组均无差异(P均>0.05)。(4)血清sCD40L水平:SF组浓度高于N组、ST组、MT组、ST+MT组(P<0.05),而N组、ST组、MT组、ST+MT组之间无明显差异(P>0.05)。(5)动脉组织CD40L表达强度:SF组表达强度明显高于其他4组(P<0.05),ST组、MT组、ST+MT组与N组无差异(P>0.05)。结论动脉粥样硬化大鼠血清和动脉组织CD40L浓度增高。他汀类药物和双胍类药物均能通过降低血脂,抑制组织CD40/CD40L表达,减轻炎症反应而起到拮抗动脉粥样硬化的作用,其中双胍类药物的降血脂作用更加明显,他汀类药物则在保护血管,改善动脉粥样硬化方面占优。两药联用的效果明显优于单用任何一种。

Objective To investigate the effect of simvastatin and mefformin on blood lipid, aortic pathological and configurational changes, serum sCIMOL level and arterial tissue CIMOL protein expression in atherosclerosis （AS） rats, and to explore the potential intervention mechanism. Methods A total of 50 healthy SD male rats, aged 8 weeks, weight about 200 g,were randomly divided into 5 groups（n = 10） ：Group N （normal control group） ,Group SF（high salt ＋ high fat group）, Group ST（ high fat plus high salt ＋ simvastatin group）, Group MT（high fat plus high salt ＋ mefformin group） ,Group ST ＋ MT（high fat plus high salt ＋ simvastatin ＋ metformin group）. After 16-week feeding,the rats in each group were detected for blood lipid, aortic pathology and configuration, serum sCIMOL level and the expression of CIMOL in arterial tissue. Results ① Blood lipid： In Group SF, total cholesterol （ TC ）, triglyceride （TG） were significantly higher than those in Group N（P 〈0.01 ） ,and no significant difference was observed between Group ST and Group N （P 〉0.05） ;TC ,TG in Group MT and Group ST ＋ MT were significantly lower than those in Group N（ P 〈 0.01 ）.② Aorta atherosclerotic pathology：Group N showed no abnormal changes in tissue structure;Group ST, Group MT and Group ST ＋ MT showed varying degree medial thickening, but no formation of typical atherosclerotic plaques; Group SF showed typical atherosclerotic plaques. ③ Aorta configuration changes：The medial thickness in each treatment group was significantly thicker than that in Group N,which was highest in Group SF but lowest in Group ST ＋ MT（SF 〉 MT 〉 ST 〉 ST ＋ MT）. The ratio of lumen area/total vascular area （LA/TVA） in Group SF was smaller than those in Group N, Group ST, Group MT, Group ST ＋ MT（P 〈 0.01 ）, no significant difference was observed between Group ST and Group MT, and between Group ST ＋ MT and Group N （ all P 〉 0.05 ）. ④ Serum sCIMOL level ： In Group SF, the serum concentration of sCD40L was higher than those in Group N, Group ST, Group MT and Group ST ＋ MT（P 〈0.05）, and no significant difference was found in sCIMOL concentration among Group N, Group ST, Group MT and Group ST ＋ MT（P 〉0.05）. ⑤ Expression of CIMOL in arterial tissues：The expression of CD40L in Group SF was higher than those in Group N, Group ST, Group MT and Group ST ＋ MT （ P 〈 0. 05 ）, and no significant difference was found in CIML expression among Group N, Group ST, Group MT and Group ST ＋ MT （ P 〉 0.05 ）. Conclusion The level of serum sCD40L and expression of CD40L in arterial tissues increase in AS rats. Both simvastatin and mefformin have an anti-atherosclerosis effect by reducing blood lipid, inhibiting the expression of CD40L and relieving inflammatory response. Biguanides drugs have a more significant effect for decreasing blood lipid while stafins drugs are better in protecting vessel and improving AS. The combination of the two drugs above is superior to either of them in effect.