基础医学与临床 ›› 2019, Vol. 39 ›› Issue (10): 1388-1392.

• 研究论文 • 上一篇    下一篇

Apelin改善慢性肾脏病大鼠血管钙化

刘莎,韩雪,郭维康,刁宗礼,刘文虎   

  1. 首都医科大学附属北京友谊医院
  • 收稿日期:2018-07-18 修回日期:2019-03-06 出版日期:2019-10-05 发布日期:2019-09-25
  • 通讯作者: 刘文虎 E-mail:liuwh0211@126.com
  • 基金资助:
    国家自然科学基金;国家自然科学基金;北京市医管局青苗计划;北京市科技计划课题

Apelin ameliorates vascular calcification of rats with chronic kidney disease

  • Received:2018-07-18 Revised:2019-03-06 Online:2019-10-05 Published:2019-09-25

摘要: 目的 探讨脂肪因子Apelin 在慢性肾脏病大鼠血管钙化中的作用。方法 将大鼠随机分为对照组(给予正常饮食)、模型组(给予0.75%腺嘌呤饮食复制血管钙化的慢性肾脏病大鼠模型)、 Apelin干预组(给予0.75%腺嘌呤饮食,并用微量泵每天持续注射Apelin-13 20 μg/kg)、Apelin处理正常大鼠组(给予正常饮食,并用微量泵每天持续注射Apelin-13 20 μg/kg),每组10只。6周后将大鼠处死,用生化法检测血清中肌酐、尿素氮、钙、磷的浓度;ELISA检测血清Apelin-13的浓度;RT-qPCR法检测主动脉中APJ和Pit-1mRNA表达;免疫组化法观察主动脉中 Runx2和骨保护素的表达;Von Kossa染色观察主动脉钙盐沉积。 结果 6周后,与对照组相比,模型组大鼠血清肌酐及尿素氮水平明显升高(P<0.01); 血钙降低、血磷升高(P<0.01);血清Apelin 水平(P<0.01)和主动脉中APJ mRNA(P<0.05)表达下降;主动脉中Runx2、骨保护素表达增加,明显钙盐沉积,Pit-1 mRNA的表达升高(P<0.05)。与模型组相比,Apelin干预组血磷下降(P<0.05);血清Apelin水平和主动脉中APJ mRNA表达量均升高(P<0.05); Runx2和骨保护素的表达下降,主动脉钙化程度减轻,Pit-1 mRNA表达减少(P<0.05)。结论 Apelin可以有效改善慢性肾脏病大鼠血管钙化。

关键词: Apelin, Pit-1, 高磷血症, 血管钙化, 慢性肾脏病

Abstract: Objective To investigate the effect of adipokine Apelin on vascular calcification of rats with chronic kidney disease. Methods The rats were randomly divided into Control group (given normal diet), Model group (given 0.75% adenine diet to induce chronic kidney disease and aortic calcification) , Apelin-treated group ( given 0.75% adenine diet and subcutaneous infusion of Apelin-13 20μg/kg daily) and Apelin-treated normal group (given normal diet and subcutaneous infusion of Apelin-13 20μg/kg daily) , n=10 separately. The rats were sacrificed at six weeks and the serum levels of Ca, P, urea nitrogen and creatinine were analyzed using an autoanalyzer. ELISA was used to evaluate the plasma level of Apelin. RT-qPCR was used to detect the mRNA expression of APJ and Pit-1 in aorta. Immunohistochemistry was used to visualize the distribution of Runx2 and osteoprotegerin in aorta. Von Kossa staining was performed to evaluate aortic calcification. Results At week 6, compared with Control group, serum urea nitrogen and creatinine concentrations increased significantly(P<0.01), serum Ca decreased, serum P increased(P<0.01), with decrease of serum Apelin (P<0.01)and mRNA expression of APJ in aorta(P<0.05), increased expression of Runx2, osteoprotegerin , obvious calcification and increased mRNA expression of Pit-1 in aorta in Model group(P<0.05). Compared with Model group, Apelin-treated group improved hyperphosphatemia(P<0.05), normalized the plasma level of Apelin and APJ mRNA expression(P<0.05), attenuated the expression of Runx2, osteoprotegerin, calcification lesion and Pit-1 mRNA expression(P<0.05). Conclusion Apelin/APJ is able to ameliorate vascular calcification of CKD rats.

Key words: Apelin, Pit-1, Hyperphosphatemia, Vascular calcification, Chronic kidney disease