肝细胞生长因子治疗冠状动脉粥样硬化大鼠的实验研究

Experimental study on the therapeutic effect of hepatocyte growth factor in rats with atherosclerosis

目的探讨肝细胞生长因子(HGF)治疗大鼠冠状动脉粥样硬化(AS)的实验效果。方法选取10周龄SPF级成年雄性SD大鼠72只,其中18只为正常组(等量生理盐水灌胃)、54只为AS模型大鼠。AS模型大鼠随机分为阳性对照组[阿托伐他汀治疗,4.8 mg/(kg·d)],实验组A[HGF,10 mg/(kg·d)]、实验组B[HGF,30 mg/(kg·d)]各18只,干预时间12周。检测并对比各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、氧化修饰低密度蛋白(ox-LDL)、内皮型一氧化氮(NO)、内皮素-1(ET-1)、过氧化物歧化酶(SOD)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及冠状动脉中CD40L、基质金属蛋白酶-9(MMP-9)蛋白的表达情况。结果模型组的血清TC、TG、LDL-C、ox-LDL、ET-1、IL-6、TNF-α水平均显著高于正常组(P<0.05),模型组HDL-C、NO、SOD水平均低于正常组(P<0.05);实验组A、实验组B及阳性对照组的TC、TG、LDL-C、ox-LDL、ET-1、IL-6、TNF-α水平均显著低于模型组(P<0.05),HDL-C、NO、SOD均显著高于模型组(P<0.05);模型组的冠脉CD40L、MMP-9蛋白水平均显著高于正常组(P<0.05);实验组A、实验组B及阳性对照组冠脉CD40L、MMP-9蛋白表达水平均显著低于模型组(P<0.05)。实验组B的TC、TG、LDL-C、ox-LDL、ET-1、IL-6、TNF-α、CD40L、MMP-9蛋白水平显著低于实验组A(P<0.05),HDL-C、NO、SOD显著高于实验组A(P<0.05)。结论 HGF治疗大鼠AS的实验疗效明显,可以显著降低血脂及炎症反应水平,减轻冠脉损伤程度。

Objective To investigate the effect of hepatocyte growth factor(HGF)on coronary atherosclerosis(AS)in rats.Methods 10 week old male SD SPF 72 rats,of which 18 for normal group(normal saline),54 AS rats(normal saline),AS rats were randomly divided into positive control group[atorvastatin,4.8 mg/(kg·d)],experimental group A[HGF,10 mg/(kg·d)],group B[HGF,30 mg/(kg·d)]with 18 rats in each group,intervention time was 12 weeks.The expression levels of TC,TG,HDL-C,LDL-C,ox-LDL,NO,ET-1,SOD,IL-6 and TNF-αin serum and CD40L and MMP-9 in coronary artery were detected and compared.Results The serum TC,TG,LDL-C,ox-LDL,ET-1,IL-6,TNF-αlevels of model group were significantly higher than those of normal group(P<0.05),HDL-C,NO,SOD in model group were significantly lower than those in the normal group(P<0.05);TC,TG,LDL-C,ox-LDL,ET-1,IL-6,TNF-αlevels of experimental group A,experimental group B and positive control group were significantly lower than those of the model group(P<0.05),HDL-C,NO and SOD were significantly higher than those in the model group(P<0.05).Coronary CD40L,MMP-9 protein levels of model group were significantly higher than normal group(P<0.05);Coronary B CD40L and MMP-9 protein expression levels of experimental group A,experimental group and positive control group were significantly lower than those in the model group(P<0.05).The levels of TC,TG,LDL-C,ox-LDL,ET-1,IL-6,TNF-α,CD40L and MMP-9 in experimental group B were significantly lower than those in experimental group A(P<0.05).HDL-C,NO and SOD were significantly higher than those in experimental group A(P<0.05).Conclusion The therapeutic effect of HGF on rats with AS is significant,which can significantly reduce the level of blood lipid and inflammatory reaction,and reduce the degree of coronary injury.