Anti-atherosclerotic effect of recombinant hirudin on ApoE-/-mice
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.After 8 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 of α-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 of α-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 vascular collagen and development of atherosclerosis in ApoE-/-mice.
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