外源性apelin-13对大鼠动脉粥样硬化形成的影响

发布时间：2018-04-15 20:44

本文选题：动脉粥样硬化 + 氧化应激　；参考：《第三军医大学学报》2014年17期

【摘要】：目的探讨外源性apelin-13多肽对大鼠动脉粥样硬化形成的影响及可能机制。方法将60只SD大鼠分为4组(n=15):正常对照组(普通饲料)、高脂模型组(高脂饲料,生理盐水尾静脉注射)、低剂量apelin组(高脂喂养同时隔天给予apelin-13 2 mg/kg尾静脉注射)、高剂量apelin组(高脂喂养同时隔天给予apelin-13 8 mg/kg尾静脉注射)。于高脂喂养伊始一次性给予后3组大鼠维生素D3(60×104U/kg)腹腔注射。12周末造模结束后,检测大鼠血脂、丙二醛(malondialdehyde,MDA)及超氧化物歧化酶(superoxide dismutase,SOD)水平;HE染色观察主动脉弓处组织形态学变化;免疫组化观察平滑肌肌动蛋白(α-SMA)及p22phox在各组血管的表达;超声观察各组腹主动脉病变情况;Western blot检测各组p22phox、NF-κB p65、JNK及p-JNK的表达。结果 1与正常对照组相比,其他3组血脂(除外HDL-C)均明显升高(P0.01)。高、低剂量apelin组较高脂模型组MDA下降,SOD升高,高剂量apelin组变化更显著(P0.01)。2病理观察:高脂模型组及低剂量apelin组主动脉内膜明显增厚、不光滑,纤维斑块形成伴大量炎症细胞浸润、胆固醇结晶及钙化病灶,呈典型动脉粥样硬化改变。高剂量apelin组大鼠主动脉内膜稍欠光滑,有轻微增厚,中层平滑肌细胞排列较紊乱,伴少量纤维增生及炎症细胞浸润。3超声检测:高脂模型组及低剂量apelin组大鼠腹主动脉内膜欠清晰、不光滑、连续性中断,管壁增厚,可见较小斑块突出于管腔。4免疫组化显示主动脉α-SMA表达:其他3组显著低于正常对照组(P0.01);高、低剂量apelin组显著高于高脂模型组(P0.01);高剂量apelin组显著高于低剂量组(P0.01)。高、低剂量apelin组的p22phox表达明显少于高脂模型组(P0.01)。5Western blot显示主动脉p22phox、NF-κB p65及p-JNK在其他3组表达显著高于正常对照组(P0.01);p22phox、NF-κB p65在高、低剂量apelin组的表达显著低于高脂模型组(P0.01);p-JNK在低剂量apelin组及高脂模型组间无差异;p22phox、NF-κB p65及p-JNK在高剂量apelin组的表达较低剂量apelin组显著减少(P0.01);各组JNK表达无明显差异(P0.05)。结论外源性apelin-13多肽能减轻氧化应激效应在大鼠动脉粥样硬化形成中的作用,能抑制平滑肌细胞增殖,减缓动脉粥样硬化发展,其机制可能是通过阻止JNK/NF-κB信号通路激活。
[Abstract]:Objective to investigate the effect of exogenous apelin-13 peptide on atherosclerosis in rats and its possible mechanism.Methods 60 Sprague-Dawley rats were divided into 4 groups: normal control group (normal diet group), high fat model group (high fat diet group).Normal saline was injected into caudal vein, low dose apelin group was given apelin-13 2 mg/kg caudal vein injection every other day, and high dose apelin group was given apelin-13 8 mg/kg tail vein injection every other day.After intraperitoneal injection of 60 脳 10 ~ 4 U / kg vitamin D ~ (3 +) at the beginning of high-fat feeding, after 12 weeks, the blood lipid, malondialdehyde (malondialdehyde) and superoxide dismutase (SOD) levels in rats were measured to observe the morphological changes of aortic arch by HE staining. The results were as follows: (1) after intraperitoneal injection of vitamin D _ (3) (60 脳 10 ~ (4) U 路kg ~ (-1)) at the beginning of high-fat feeding, the tissue morphology of aortic arch was observed by HE staining.The expression of smooth muscle actin (伪 -SMA) and p22phox in each group was observed by immunohistochemistry, and the expression of p22phox- 魏 B p65 blot and p-JNK in each group were detected by ultrasound.Results 1 compared with the normal control group, the serum lipids (excluding HDL-C) in the other three groups were significantly higher than those in the control group (P 0.01).The changes of MDA in high and low dose apelin group were higher than that in high fat model group, and the changes in high dose apelin group were more significant than those in high fat model group and low dose apelin group. The intima of aorta in high fat model group and low dose apelin group were obviously thickened and not smooth, and fibrous plaque formation accompanied with a large number of inflammatory cells infiltration.Cholesterol crystallized and calcified lesions showed typical atherosclerotic changes.In the high dose apelin group, the aortic intima was slightly unsmooth, slightly thickened, and the medial smooth muscle cells were disordered.The abdominal aorta intima of rats in high fat model group and low dose apelin group was unclear, not smooth, continuity was interrupted, and the wall of the aorta was thickened.The expression of 伪 -SMA in the aorta of the other three groups was significantly lower than that of the normal control group (P 0.01), the high and low dose apelin group was significantly higher than that of the hyperlipidemia model group (P 0.01), and the high dose apelin group was significantly higher than the low dose group (P 0.01).The expression of p22phox in the high and low dose apelin group was significantly lower than that in the hyperlipidemic model group (P 0.01). 5 Western blot showed that the expression of p22phoxtr NF- 魏 B p65 and p-JNK in the other three groups were significantly higher than those in the control group.There was no significant difference in the expression of p22phoxanNF- 魏 B p65 and p-JNK between the low dose apelin group and the high fat model group compared with the low dose apelin group, but the expression of JNK in the low dose apelin group was significantly lower than that in the low dose apelin group, but there was no significant difference in the expression of JNK in each group compared with the low dose apelin group.Conclusion exogenous apelin-13 peptide can attenuate the role of oxidative stress in the formation of atherosclerosis in rats, inhibit the proliferation of smooth muscle cells and slow down the development of atherosclerosis. The mechanism may be by blocking the activation of JNK- / NF- 魏 B signaling pathway.
【作者单位】：重庆医科大学附属第二医院心内科;
【分类号】：R543.5

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