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(P<0.01)。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(P<0.01)。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(P<0.01);高、低剂量apelin组显著高于高脂模型组(P<0.01);高剂量apelin组显著高于低剂量组(P<0.01)。高、低剂量apelin组的p22phox表达明显少于高脂模型组(P<0.01)。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(P<0.01);p22phox、NF-κB p65在高、低剂量apelin组的表达显著低于高脂模型组(
Objective To determine the effects of exogenous apelin-13 peptide on the formation of atheroselerosis in rats, and investigate its possible underlying mechanisms. Methods A total of 60 SD rats （7 to 8 months old, weighing 170 to 220 g） were randomly divided into 4 groups （ n = 15 ）, that is, normal control group （ group N, fed with normal diet）, model group （ group M, fed with high fat diet, every 2 d given normal saline through caudal vein）, low-dose apelin-13 group （group LA, fed with high fat diet, every 2 d receiving 2 mg/kg apelin-13 through caudal vein） , and high-dose apelin-13 group （ group HA, fed with high fat diet, every 2 d given 8 mg/kg apelin-13 through caudal vein）. In the beginning of high-fat feeding, the rats of latter 3 groups were injected intra-peritoneally with 60 × 10^4 U/kg vitamin D3 for one time. At the end of 12 weeks＇ feeding, the rats＇ blood samples were harvested for their serum lipids levels, malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in each group. Ultrasound examination was used to observe abdominal aortic lesions. After all rats were killed, their aortic arches were collected. HE staining was employed to observe the morphological changes of artery tissue, immunohistochemical assay to detect the expression of smooth muscle actin （α-SMA） and p22phox, and Western blotting to detect the expression ofp22phox, NF-κB p65, JNK and p-JNK. Results Compared with group N, the lipids of the other 3 groups were significantly increased besides HDL-C （P 〈0.01 ）. The MDA content was significantly lower, while SOD activity was higher in group LA and group HA than in group M, with those in group HA more significant （P 〈 0.01 ）. HE staining indicated that the group M and group LA had significantly thickened and unsmooth intima in the aortic arch, with many fibrosis plaques, inflammatory cells infiltration, cholesterol crystal and calcification, suggesting obvious typical signs of atheroselerosis. In HA group, the sligh
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2014年第17期1822-1827,共6页
Journal of Third Military Medical University
