| AIM:To investigate the lipid fluctuation, aortic configuration, serum sCD40L levels and arterial tissue CD40/CD40L expression intensity changes induced by high fat plus high salt chow in rats. As well as, to explore the potential intervention mechanism of simvastatin and metformin on atherosclerosis.METHODS:1.Animal grouping:A total70healthy SD male rats, aged8weeks, weight about200g, were randomly divided into7groups(n=10):N group(normal control group), S group(high salt group), F group(high fat group), SF group(high salt+high fat group),ST group(high fat plus high salt+simvastatin group),MT group(high fat plus high salt+metformin group),ST+MT group(high fat plus high salt+simvastatin+metformin group).2.Animal feeding:N group:standard diet; S group:high salt diet; F group:high fat diet; SF group:high fat plus high salt diet; ST group:high fat plus high salt diet+simvastatin; MT group:high fat plus high salt diet+metformin; ST+MT group: high fat plus high salt diet+simvastatin+metformin.3. Specimens drawn:After16weeks fed, the rats were anesthetized, upon about3ml abdominal aorta blood were subject to determine the lipid profile and serum sCD40L level (enzyme-linked immunosorbent assay),and about lcm ascending aorta root were removed and immobilized, and then slices were taken to perform HE staining to observe the aortic conformational changes as well as immunohistochemisty to determine the expression intensity of CD40/CD40L inthe vessel wall.RESULTS:1.Lipid profile: In F group and SF group, lipid profile wassignificantly higher than in N group(p＜0.01), and no significant differencebetween S group, ST group and N group was observed. Lipid profile in MTgroup and ST+MT group was significantly lower than in N group(p＜0.01).2. Arterial pathology: N group showed no abnormal changes in tissuestructure; S group, ST group, MT group and ST+MT group showed varyingdegree medial thickening, but not formation of atherosclerotic plaques; F groupindicated obviously membrane thickening, atherosclerotic plaques was found inthe partial. SF group showed typical atherosclerotic plaque changes: vascularendothelium continuity is damaged, wall thickening, partial wall to the lumen,formation plaque within the necrotic material and elastic fibers rupture,adventitia thinning and teared.3. Aorta configuration changes: The aorta configuration in S group, F group,and SF group was obviously abnormal. The thickness of intimal media in Sgroup and F group was thicker than that in N group（p＜0.05）, and the medialthickness in SF group was significantly thicker than that in N group（p＜0.01）.The ratio of lumen area/total vascular area (LA/TVA) in S group and F groupwas smaller than that in N group（p＜0.05）, and the ratio of LA/TVA in SFgroup was significantly smaller than in N group（p＜0.01）. The medial thicknessin ST group and MT group was thinner than that in SF group（p＜0.05）, and themedial thickness in ST+MT group was significantly thinner than that in SFgroup（p＜0.01）, but did not reach the level of N group.4. Serum sCD40L level: In S group, F group and SF group, the serumconcentrations of sCD40L were higher than that in N group, ST group, MTgroup and ST+MT group (p<0.05), meanwhile that in SF group was also higherthan in S group and F group (p<0.05).However, no significant difference ofsCD40L concentration between S group and F group as well as N group, STgroup, MT group and ST+MT group was observed (p＞0.05).5. Arterial tissue CD40/CD40L expression: The expression of CD40/CD40L in the ascending aorta in S group, F group and SF group was higher than that in N group, ST group, MT group and ST+MT group (p<0.05), and that in SF group was also higher than in S group and F group (p<0.05), and no significant difference of CD40/CD40L expression between S group and F group as well as N group, ST group, MT group and ST+MT group was found (p>0.05).CONCLUSIONS:1.The formation of atherosclerosis could be induced by simple high-fat diet in rats, however, that was not obviously in rats when fed by simple high-salt chow. Typical atherosclerosis plaque could be observed in rats when fed by high-salt plus high-fat chow.2. High-salt and high-fat diet could induce atherosclerosis in rats, accompanied by a heighten in serum concentrations of sCD40L and enhance in the expression of CD40/CD40L in artery, which suggested that high-salt and high-fat could lead to arterial tissue lesions by inflammation pathways in response to vascular injury.3. Both simvastatin and metformin could have an anti-atherosclerosis effect but simvastatin seemed to have a stronger effect, among which the effect of anti-atherosclerosis of combined treating group was obviously higher than a single drug. Which may by related to improving blood lipids, decreasing serum sCD40L and arterial CD40/CD40L. |
PDF Full Text Request