艾塞那肽对ApoE-/-小鼠动脉粥样硬化血清抵抗素的影响

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摘要目的探讨艾塞那肽对蛋白E基因敲除（ApoE-/-）小鼠动脉粥样硬化血清抵抗素的影响。方法选取高脂喂养的6周龄载脂ApoE-/-雄性小鼠30只，按随机数字表法将其分模型组（n = 15）与艾塞那肽组（n = 15），艾塞那肽组给予艾塞那肽1.0 nmol/（kg·d），腹膜下注射，2次/d。选取高脂喂养的同龄、同遗传的背景野生型C57BL/6J雄性小鼠作对照组（n = 15）。12周后处死并收集血清，并采用自动生化分析仪测定检测总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、三酰甘油；采用酶联免疫吸附法测定抵抗素、肿瘤坏死因子-α（TNF-α）及白细胞介素6（IL-6）的含量；主动脉根部作病理切片、苏木精-伊红（HE）染色并测量校正的斑块面积。结果模型组的总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及三酰甘油水平显著高于对照组（P < 0.01）；艾塞那肽组的总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及三酰甘油与模型组比较，差异无统计学意义（P ＞ 0.05）。模型组的抵抗素、TNF-α及IL-6水平与对照组比较，显著升高（P < 0.01），艾塞那肽组的抵抗素、TNF-α和IL-6含量与模型组比较，显著降低（P < 0.01）；艾塞那肽组的主动脉粥样硬化校正斑块面积明显小于模型组（P < 0.05）。结论艾塞那肽可有效降低动脉粥样硬化小鼠的血清抵抗素水平，从而抑制炎性反应及动脉粥样硬化斑块进展，这可能是胰高血糖素样肽-1受体激动剂抗动脉粥样硬化的机制之一。

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	邓国雄韦金儒陈梅香

关键词 ：艾塞那肽, 动脉粥样硬化, 抵抗素, 胰高血糖素样肽-1

Abstract：Objective To investigate the effect of Exenatide on serum resistin in atherosclerosis of apolipoprotein E knockout (ApoE-/-) mice. Methods Thirty six-week-old ApoE-/- male mice fed with high fat were randomly divided into model group (n = 15) and exenatide group (n = 15). The exenatide group was given Exenatide 1.0 nmol/(kg·d), subperitoneal injection twice a day. Male C57BL/6J mice fed with high fat were selected as control group (n = 15). After 12 weeks, the serum was collected and the levels of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglyceride were measured by automatic biochemical analyzer. The contents of resistin, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay. The aortic root was pathologically sliced and stained with hematoxylin-eosin (HE), and the corrected patch area was measured. Results The levels of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride in the model group were significantly higher than those in the control group(P < 0.01). There was no significant difference in total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride between the exenatide group and the model group (P > 0.05); the levels of resistin, TNF-α and IL-6 in the model group were significantly higher than those in the control group (P < 0.01), while the contents of resistin, TNF-α and IL-6 in the exenatide group were significantly lower than those in the model group (P < 0.01). The area of corrected atherosclerosis plaque in the exenatide group was significantly smaller than that in the model group (P < 0.05). Conclusion Exenatide can effectively reduce the level of serum resistin in atherosclerotic mice, thereby inhibiting inflammatory response and atherosclerotic plaque progression, which may be one of the mechanisms of glucagon-like peptide-1 receptor agonists in anti-atherosclerosis.

Key words： Exenatide Atherosclerosis Resistin；Glucagon-like peptide-1

基金资助:国家自然科学基金资助项目（81260059）；
广西壮族自治区南宁市科技局立项课题（20163129）。

通讯作者: 韦金儒（1964.4-），男，博士，教授，硕士生导师，院长；研究方向：冠心病的基础与临床。

作者简介: 邓国雄（1978.9-），男，硕士；研究方向：冠心病的基础和临床。

引用本文:

邓国雄韦金儒陈梅香. 艾塞那肽对ApoE-/-小鼠动脉粥样硬化血清抵抗素的影响[J]. 中国医药导报, 2019, 16(13): 4-7,11.
DEND Guoxiong WEI Jinru CHEN Meixiang. Effect of Exenatide on serum resistin in ApoE-/- mice with atherosclerosis. 中国医药导报, 2019, 16(13): 4-7,11.

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