The Roles Of Inflammatory Factors In The Formation Of Atherosclerosis

Part I[Objective] To explore the roles of interlekin-17、interlekin-10and matrix metalloproteinase-12in the pathogenesis of atherosclerosis, and further to understand the intervention of atorvastatin on atherosclerosis.[Methods] Twenty-one Japanese big ear rabbits were randomly divided into3groups:control group(n=7), model group(n=7) and intervention group(n=7). The control group with ordinary diet, the model group with high-fat diet,the intervention group with high-fat diet and atorvastatin (5mg.kg-1.d-1),respectively for12weeks. Serum total cholesterol(TC)、triglyceride(TG),high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C) were determined by enzymic colorimetric and precipitation separation method;The expressions of interleukin-17、interleukin-10、matrix metalloproteinase-12were measured by double antibody sandwich enzyme-linked immunosorbent assay(ELISA),The pathological morphology changes of atherosclerosis were observed by HE staining; Endometrial thickness、intimal-medial ratio、plaque area and plaque percentage were measured through image analysis software.[Results] The study showed that serum TC、TG、LDL-C、IL-17and MMP-12levels in the intervention group were significantly lower than those in the model group(P<0.05, for all), and higher than control group(P<0.05,for all). Whereas, no significant change of the level of HDL-C was seen in the three groups(P>0.05). the level of interleukin-10in the intertention group was higher than the model group and control group (P<0.05,for all); The endometrial thickness、intimal-medial ratio、 plaque area and plaque percentage in the intervention group were all significantly lower than the model group (P<0.05,for all); Correlation analysis showed that the serum of interleukin-17and matrix metalloproteinase-12levels were positively correlated with plaque percentage (r=0.847,P=0.001; r=0.839,P=0.001),but the level of interleukin-10was negatively correlated with plaque percentage (r=-0.794,P=0.002). In comparison with each other, the level of interleukin-17was positively correlated with the level of matrix metalloproteinase-12(r=0.709,P=0.001), and was negatively correlated with the level of interleukin-10(r=-0.738,P=0.000). the level of matrix metalloproteinase-12was negatively correlated with the level of interleukin-10(r=-0.563,P=0.015)[Conclusion] It is a relatively mature molding technology through the high-fat diet to establish the models of rabbit atherosclerosis,and owns high success rate,moreover,the lesion of atherosclerosis is similar to the human’s atherosclerotic lesion so that the models can be used in experimental study.The elevated levels of interleukin-17、matrix metalloproteinase-12and decreased level of interleukin-10illustrates that inflammatory factors play an important role in the pathogenesis of atherosclerosis. In addition to lipid lwering function, atorvastatin can depress the chronic inflammatory response of artery in order to resist atherosclerosis by depressing the expressions of interleukin-17and matrix metalloproteinase-12,also improving the expression of interleukin-10. Part Ⅱ[Objective] To investigate the effects of interlekin-17、interlekin-10and matrix metalloproteinase-12on the vulnerability of carotid atherosclerotic plaque and cerebral infarction.[Methods] The case group was divided into2groups:asymptomatic carotid atherosclerosis(ACAS)group、acute atherosclerotic cerebral infarction (AACI) group according to whether or not the clinical stroke incidence took place;These cases were also divided into vulnerable plague (VP) group and unvulnerable plague (UVP)group according to the results of ultrasonic inspection.Separately to establish’ the control group. The plasma levels of these cytokines in subjects were tested by enzyme-linked immunosorbent assay (ELISA)[Results] Compared with the control group, the concentrations of IL-17and MMP-12in AC AS group and AACI group had significantly elevated(P=0.000,for all), moreover, in AACI group, the concentrations of IL-17and MMP-12were higher than the ACAS group(P=0.000;P=0.002).In AACI group, the level of IL-10was lower than the ACAS group and control group(P=0.000,for all). Whereas, no significant change of the level of IL-10was seen in ACAS group and control group(P=0.275). In VP group, the concentrations of IL-17and MMP-12were higher than the UVP group(P=0.000;P=0.014).In VP group, the level of IL-10was lower than the UVP group and control group(P=0.000,for all). Whereas, no significant change of the level of IL-10was seen in UVP group and control group(P=0.742).In comparison with each other, the level of IL-17was positively correlated with the level of MMP-12(r=0.640,P=0.000), and was negatively correlated with the level of IL-10(r=-0.430,P=0.000). the level of MMP-12was weakly negatively correlated with the level of IL-10(r=-0.242,P=0.013)[Conclusion]IL-17、IL-10and MMP-12may participate the pathological process of atherosclerosis and cerebral infarction, elevated IL-17and MMP-12levels plus decreased IL-10level may be closely correlated with the plagues’vulnerability. The results would be helpful to discover the vulnerability of plagues in the early stage and to predict the incidence of acute ischemic stroke.