二甲双胍对高盐高脂摄入致大鼠主动脉重构的干预研究

Retarding effect of metformin on artery remodeling induced by high-salt plus high-fat diet in rats

目的探讨二甲双胍对高盐高脂摄入致大鼠主动脉重构的干预作用。方法选取36只成年雄性SD大鼠,随机分为3组(n=12):对照组(C组)、高盐高脂组(SF组)和二甲双胍治疗组(T组),C组予标准饲料,SF组及T组高盐高脂饲料喂养,T组加用二甲双胍灌胃。16周后,测量大鼠动脉压、血清甘油三酯(TG)、总胆固醇(TC)及可溶性CD40L(sCD40L)浓度;免疫组化法检测升主动脉根部血管壁组织CD40L的表达;HE染色测量升主动脉起始段中膜层厚度和动脉内腔面积与血管腔横断面积比值。结果 (1)SF组收缩压与C组相比明显增高(P<0.01),而T组较SF组明显降低(P<0.05),但未达到C组水平;(2)SF组TC、TG水平较C组明显升高(P<0.01),而T组TC、TG水平较SF组明显下降(P<0.01);(3)SF组中膜厚度(IMT)较C组显著增厚(P<0.01),血管内腔面积明显缩小(P<0.01)而血管横断面积增加(P<0.01)。T组中膜厚度较SF组变薄(P<0.01)但未达到C组水平;(4)SF组血清sCD40L浓度高于C组和T组(P<0.01)。C组T组之间差异无统计学意义(P>0.05);(5)SF组动脉组织CD40L表达强度明显高于C组和T组(P<0.05),T组与C组差异无统计学意义(P>0.05)。结论二甲双胍可以通过降低血压,调节血脂代谢,抑制CD40系统,起到血管保护作用。

Objective To investigate the effect of metformin on artery remodeling induced by high-salt plus high-fat diet in Rats. Methods Thirty six adult male SD rats were randomly divided into 3 groups （n = 12） ：control （C） group, high salt ＋ high fat （SF） group and high metformin treatment （T） group,gnupc fed ith standard diet others fet with highsah and hegh fat, and group t were comined with metfonmin After fed by a different diet for 16 weeks, the rats were subjected to determine blood pressures and ser- um concentrations of triglycerides （TG）, total cholesterol （TC） and soluble CIM0 ligand（sCD40L）. The expression of CD40/CD40L in the root of ascending aorta was detected by immunohistochemical. The thickness of intima media in the ascending aorta as well as the ratio of lumen area/total vascular area were measured and calculated after HE staining. Results （ 1 ） In group SF, systolic blood pressure was significantly higher than that in group C （P 〈 0.01 ）, Systolic blood pressure in group T were slightly higher than that in group C but significantly lower than that in group SF （P 〈 0.05）. （2） TC and TG level of rats in group SF was significantly higher than that in group C （P 〈 0.01 ）. And the TC,TG level of group T was significantly decreased compared with group SF （ P 〈 0.01 ）. （3） Compared with group C, intimal-medial thickness（IMT） in group SF was significantly thicker （P 〈 0.01 ） , the lumen area was smaller （P 〈0.01 ） ,but the total vascular area was increased（P 〈0.01 ）. IMT in group T was thinner than that in group SF but more thicker than that in group C. （4） In group SF,the serum concentrations of sCD40L were higher than that in group C and group T （P 〈 0.01 ） ; no significant difference of sCD40L concentration between group C and group T （ P 〉 0.05 ）. （5） The expression of CD40/ CD40L in the ascending aorta in group SF was significantly higher than that in group C and group T （ P 〈 0.05 ）, No significant differ- ence of CD40/CD40L expression between group C and T was observed. Conclusion Metformin can prevent atherosclerosis by regu- lating lipid metabolism,lowering blood pressure and down-regulating the expression of CIMO and CIMOL system.