重组水蛭素抗ApoE^(-/-) 小鼠动脉粥样硬化的研究  

Anti-atherosclerotic effect of recombinant hirudin on ApoE^(-/-)mice

作　　者：赖宗强 赖吴芳 韦文兴 张晓慧 黎渊弘[1] LAI Zongqiang;LAI Wufang;WEI Wenxing(The Second Affiliated Hospital of Guangxi Medical University,Guangxi,Nanning 530007,China)

机构地区：[1]广西医科大学第二附属医院,南宁市530007 [2]广西壮族自治区北海市人民医院

出　　处：《河北医药》2024年第11期1617-1621,共5页Hebei Medical Journal

基　　金：广西自然科学基金面上项目(编号:2020GXNSFAA238042);广西医科大学第二附属医院院内课题(编号:EFYKY170004)。

摘　　要：目的探讨重组水蛭素对ApoE^(-/-)小鼠动脉粥样硬化血脂水平和粥样斑块的影响。方法高脂饲料喂养雄性ApoE^(-/-)小鼠随机分为模型组和重组水蛭素低、中、高剂量给药组,正常饮食的C57BL/6J小鼠作为正常对照组。连续给药8周后,检测血脂水平;HE染色以及Masson染色观察主动脉血管病理学改变;CD68、α-SMA免疫组织化学染色分别观察重组水蛭素对粥样斑块中巨噬细胞浸润和平滑肌肌动蛋白的影响。结果与模型组比较,重组水蛭素各剂量给药组的血清总胆固醇、三酰甘油和低密度脂蛋白胆固醇水平均有不同程度的降低(P<0.05);各给药组与模型组的高密度脂蛋白胆固醇的差异无统计学意义(P>0.05);Masson染色显示模型组主动脉血管胶原异常增生,而各给药组胶原含量均有不同程度减少;CD68、α-SMA免疫组织化学染色显示,模型组主动脉粥样斑块处有大量CD68表达和少量α-SMA表达,而重组水蛭素各给药组粥样斑块处CD68表达减少(表示巨噬细胞浸润减少)、α-SMA表达增加(P<0.05)。结论重组水蛭素能降低ApoE^(-/-)小鼠血清血脂水平,延缓平滑肌细胞凋亡,抑制血管胶原增生,从而抑制动脉粥样硬化的发展。Objective To investigate the anti-atherosclerotic effects of recombinant hirudin on blood lipid levels and atherosclerotic plaques in ApoE^(-/-)mice.Methods Male ApoE^(-/-)mice fed with a high-fat diet were randomly divided into the model group and the low-dose,medium-dose,and high-dose recombinant hirudin groups.C57BL/6J mice fed a normal diet were taken as the control group.AfteR8 weeks of continuous administrations,serum lipid levels were detected.The hematoxylin and eosin(HE)staining and Masson staining were used to observe the pathological changes in aortic vessels.The effects of recombinant hirudin on macrophage infiltration and smooth muscle actin in atherosclerotic plaques were observed by immunohistochemical staining of CD68 and alpha-smooth muscle actin(α-SMA),respectively.Results Compared with those of the model group,serum total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)in low-dose,medium-dose,and high-dose recombinant hirudin groups significantly decreased to varying degrees(P<0.05).There was no significant difference in high density lipoprotein cholesterol(HDL-C)between model group and recombinant hirudin groups(P>0.05).Masson staining showed that the collagen of aortic vessels in the model group was abnormally proliferated,while the collagen content in low-dose,medium-dose,and high-dose recombinant hirudin groups was reduced to varying degrees.Immunohistochemical staining showed a high positive expression of CD68 and low positive expression ofα-SMA in the atherosclerotic plaque of the model group.The positive expression of CD68 was significantly reduced in the atherosclerotic plaque of low-dose,medium-dose,and high-dose recombinant hirudin groups,suggesting the decreased macrophage infiltration(P<0.05).The positive expression ofα-SMA in recombinant hirudin groups was significantly enhanced(P<0.05).Conclusion Recombinant hirudin can reduce the serum blood lipids and inhibit the apoptosis of smooth muscle cells,proliferation of vasculaRcollagen and development o

关 键 词：动脉粥样硬化 重组水蛭素 血脂水平 巨噬细胞 

分 类 号：R972.6[医药卫生—药品]