首都医科大学学报 ›› 2022, Vol. 43 ›› Issue (5): 674-679.doi: 10.3969/j.issn.1006-7795.2022.05.002

• 肾脏病基础与临床研究 • 上一篇    下一篇

共享外周循环对糖尿病肾病小鼠肾损伤的影响

黄琪1, 周亦伦1*, 孙雪峰2*   

  1. 1.首都医科大学附属北京天坛医院肾内科,北京 100050;
    2.中国人民解放军总医院肾内科 肾脏疾病国家重点实验室,北京 100853
  • 收稿日期:2022-05-09 出版日期:2022-10-21 发布日期:2022-10-25
  • 基金资助:
    国家自然科学基金(81900662)。

Effect of shared peripheral circulation on renal injury in diabetic kidney disease mice

Huang Qi1, Zhou Yilun1*, Sun Xuefeng2*   

  1. 1. Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
    2. Department of Nephrology, Chinese People's Liberation Army General Hospital, State Key Laboratory of Kidney Disease, Beijing 100853, China
  • Received:2022-05-09 Online:2022-10-21 Published:2022-10-25
  • Contact: * E-mail:zhouyilun2008@sina.cn, xfssun@126.com
  • Supported by:
    National Natural Science Foundation of China(81900662).

摘要: 目的 构建野生小鼠与糖尿病肾病(diabetic kidney disease, DKD)小鼠的连体动物模型,使得DKD小鼠与野生小鼠共享外周循环,探讨外周循环改变对DKD的作用。方法 将8周龄C57BL/6J雄性小鼠与同品系、同性别、链脲佐菌素(streptozocin,STZ)诱导的不同DKD时期的小鼠(8周龄时STZ造模,分别取造模后12、20、28周)构建连体模型。连体8周后处死动物,分别采集各组小鼠的血液、尿液和肾脏组织标本。结果 共获得24对连体小鼠,DKD 12周、20周及28周各8对,以无外周循环支持的同时期DKD小鼠作为阳性对照组,以同龄野生小鼠作为阴性对照组。与阳性对照组相比,接受共享外周循环的DKD小鼠无论是DKD 12周、20周还是28周,其血糖、胰岛素、三酰甘油及总胆固醇浓度均明显减低。自DKD 20周开始,接受共享外周循环的DKD小鼠,其尿蛋白/肌酐浓度明显低于阳性对照组,该优势在DKD 28周时更为显著。此外,DKD 28周时,阳性对照组的肾脏组织损伤程度及纤维化标志物蛋白表达明显高于接受共享外周循环的DKD小鼠。结论 共享外周循环可降低DKD小鼠的血糖浓度、增强其胰岛素敏感性、调节脂质代谢,进而减轻肾脏组织损害,改善肾脏纤维化,保护肾功能。

关键词: 糖尿病肾病, 外周循环, 连体动物模型

Abstract: Objective To investigate the effects of the shared peripheral circulation on diabetic kidney disease (DKD).Methods Parabiotic surgery was performed between the 8-week-old male C57BL/6J mice and the DKD male mice of the same strain, the DKD mice was induced by streptozocin (STZ) injection and divided into three groups based on the stage of DKD: 12 weeks after STZ injection, 20 weeks after STZ injection, and 28 weeks after STZ injection. The animals were sacrificial 8 weeks after parabiotic surgery,and the blood, urine and kidney tissue samples of mice in each group were collected. Results A total of 24 pairs of parabiosis mice were obtained, 8 pairs in DKD 12 weeks, 8 pairs in DKD 20 weeks and 8 pairs in DKD 28 weeks. DKD mice in the same stage without peripheral circulation were set as the positive control group, and wild mice of the same age as the negative control group.The levels of blood glucose, insulin, triglyceride and total cholesterol in DKD with shared peripheral circulation group were significantly lower than those in the positive control group throughout all stage of DKD. In the DKD 20 weeks, the level of albumin-to-creatinine ratio in the group receiving shared peripheral circulation was significantly lower than that in the positive control group, with superiority was more significant in the DKD 28 weeks. In addition, in the DKD 28 weeks, the degree of renal injury and the expression of fibrosis marker protein in the positive control group were significantly higher than those in DKD mice receiving shared peripheral circulation. Conclusion Shared peripheral circulation could reduce blood glucose level, enhance insulin sensitivity and regulate lipid metabolism in DKD mice, and then alleviate renal tissue damage, improve renal fibrosis and protect renal function.

Key words: diabetic kidney disease, peripheral circulation, parabiosis animal model

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