| Objective:To observe the express of P-selectin,MMP-2 in carotid artery of diabetic rats before and after simvastatin intervention, and explore the protective effect on macrovascular of diabetic rats.Methods:Fifty-four male Wistar rats(weight from 190 to 230 gram) were randomly divided into control group(A,n=18),diabetes mellitus group(B,n=18)and Simvastatin intervention group (C,n=18). After fasting 12 hours, diabetes mellitus group and Simvastatin intervention group were injected intraperitoneally streptozotocin(STZ) 55mg/kg which was dissolved in citral buffer with pH=4.3, 0.1mmol/l,72 hours later, the blood sugger of diabetes mellitus group above 16.7mmol/l were regarded as the success of diabetes mellitus rats model; while the control ones were injected intraperitoneally the same volume of citral buffer. After one week of succession of the models, beginning to lavage to intervention group with Simvastatin 10mg.kg-1.d-1 dissolved in Sodium Chloride, then the other two groups with the same volume Sodium Chloride. A total of 12 feeding Weeks, at weeks of 4,8 and 12, each group took 6 rats, measured body weight one time per week, blood sugar one time every 2 weeks. In the early morning, picked air abdominal venous blood, separated serum, tested every biochemical index. Carotid arterial tissues pathological changes were examiated by light microscopy. Examining serum and carotid artery tissue' P-election, MMP-2 expression in quantitative and location by enzyme-free Phytophthora assay (ELISA) and immunohistochemical method.Results:1) The rats of group A were in fine fettle, bright and clean hair, normal growth and development. The rats of group B and group C were all into the mold, duration of test have shown polydipsia, polyphagia, polyuria, weight loss, growth retardation, sluggishness of mind, slow, dull, erect dull hair, lying curled extrados and other symptoms.2) Injection of STZ 72 hours later, fasting blood glucose of the rats of group B and C were significantly higher than group A(P<0.05); however there aren't significant differences statistically between group B and group C (P>0.05). Compared with groupA, fasting insulin of group B and C were significantly lower than group A (P<0.05); however there aren't significant differences statistically between group B and group C (P>0.05).3) Compared with groupA,, TC, TG, LDL-C levelsof the rats of group B and C gradually increased(P<0.05), HDL-C gradually reduced(P<0.05);compared with the group B, the levels of TC, TG, LDL-C of group C decreased, the difference was significant statistically(P<0.05), while the increase of HDL-C was not significant statistically (P> 0.05).4) The expression of serum P-selectin and MMP-2 of rats of group B and C were significantly higher than the group A, the difference was significant statistically(P<0.01); compared with the group B, the expression of serum P-selectin and MMP-2 of rats of group C were lower, the difference between group B and C was significant statistically(P<0.01).5) With the prolonging of duration of DM, compared with groupA,carotid artery intima-media thickness of group Band C were thicker than group A at weeks 8 and 12 after the treatment (P<0.05); however carotid artery intima-media thickness of group C was significantly lower than group B (P<0.05).6) Observed by light microscope:endothelial cells and smooth muscle cells of rats of group A in carotid artery were regular in arrangement, the full structure, the coherent elastic layer of intima-media, and the thickness of carotid artery was not obvious;in the group B, endothelial cells in carotid artery were regular in arrangement,and smooth muscle cells in the media presented slight hyperplasia at weeks 4, and with the prolonging of duration of DM, gradually it presented disordered arrangement of endothelial cells, and smooth muscle cells in proliferation, even foamy macrophages, all of these resulting in the markedly thickened arteriole and narrowing of the lumen; but after the treatment, the changes mentioned above were improved in group C.7) The results of immunohistochemistry showed that there were a little expression of P-selectin and MMP-2 could be seen in endothelial cells and smooth muscle cells of rats of carotid artery in group A, compared with the group A, the expression of P-selectin and MMP-2 were higher in the group B and C(P<0.05), and the group C was lower than group B (P<0.05),Conclusion:This research has found that P-selectin, MMP-2 already existed early in serum and carotid artery tissues of diabetic rats,as the disease progress, the expression of P-selectin, MMP-2 were obviously. The expression of P-selectin and MMP-2 were positive correlation with IMT respectively; By influencing the expression of P-selectin and MMP-2,simvastatin could inhibite vascular endothelial inflammation,smooth muscle cell proliferation and migration,even formation of foam cells. Finally delayed the process of carotid atherosclerosis,so that played the protective effect of large vessels.
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