基础医学与临床 ›› 2018, Vol. 38 ›› Issue (9): 1292-1297.

• 研究论文 • 上一篇    下一篇

倍半萜内酯减轻糖尿病小鼠胰岛素抵抗及早期肾损伤

邱维1,张薇1,陶建瓴1,王海云1,郑法雷2,李雪梅1   

  1. 1. 北京协和医院
    2. 中国医学科学院 北京协和医学院 北京协和医院 肾内科
  • 收稿日期:2017-09-05 修回日期:2018-07-05 出版日期:2018-09-05 发布日期:2018-09-10
  • 通讯作者: 李雪梅 E-mail:lixmpumch@126.com
  • 基金资助:
    NF-κB抑制剂小白菊内酯延缓抵抗素介导炎症和糖尿病肾病发生

Sesquiterpene lactones alleviate insulin resistance and early renal injury in diabetic mice

  • Received:2017-09-05 Revised:2018-07-05 Online:2018-09-05 Published:2018-09-10

摘要: 目的 观察C57BKS db/db小鼠胰岛素抵抗、慢性炎性反应及糖尿病肾病进展,并探讨倍半萜内酯(PTN)的作用。方法 以db/m鼠为对照组(db/m),db/db鼠为实验组(db/db),后者腹腔注射PTN(1.0 mg/kg 隔日一次)为干预组(db/db+PTN)。于8、12和16周取血、尿及肝肾组织,酶法测定血尿生化指标、ELISA检测血单核细胞趋化蛋白1(MCP-1)及IL-6含量,肝脏病理HE、肾脏PAS染色及免疫组化染色检测NF-кB、MCP-1表达。结果 1)与db/m组相比,db/db组小鼠出现血糖、血脂、胰岛素及尿白蛋白显著升高(p<0.05),肝脏脂肪化、肾小球肥大及基质扩张表现,血清及肾脏局部炎性因子表达增加(p<0.05);2)与db/db组相比,12周db/db+PTN组血清MCP-1、IL-6以及肾脏NF-кB和MCP-1表达减低(p<0.05);16周db/db+PTN组胰岛素抵抗指数下降(p<0.05),肾小球肥大、系膜基质增生与肝脏脂肪化减轻。结论 PTN可减少慢性炎性反应及胰岛素抵抗,从而改善肝脏脂肪化及早期糖尿病肾病预后。

关键词: 关键词: 糖尿病肾病、胰岛素抵抗、慢性炎症、倍半萜内酯

Abstract: Objective To observe the state of insulin resistance and chronic inflammatory in C57BKS db/db mice, and to investigate the role of sesquiterpene lactones (pathenolide, PTN). Methods The db/m mice were injected with normal saline (db/m+NS) as control group, db/db mice with normal saline (db/db+NS) as experimental group and db/db mice with intraperitoneal injection of PTN(1.0 mg/kg qod)as intervention group (db/db+PTN). In 8, 12 and 16 weeks the blood, urine sample, kidney and liver were taken from the mice. Tests had been made on albumin, creatinine, glucose, lipids, insulin (radioimmunoassay), MCP-1, IL-6 (ELISA) in serum and albumin, creatinine in urine. And the semi-quantitive analysis of tissue MCP-1 and NF-кB levels were also done through immunohistochemistry method. Results 1) db/db mice had elevated blood lipids, fatty liver and other metabolic abnormalities such as hyperglycemia, hyperinsulinemia and insulin resistance. The level of urinary albumin was increased and pathology showed enlargement of glomerulus and matrix. And inflammation factor increased significantly both in serum and kidney. 2) After the therapy of PTN, both the serum MCP-1, IL-6, NF-kB and the NF-кB, MCP-1 expression in the kidney in 12 weeks old db/db mice were significantly lower than the db/db group. The level of HOMA-IR in db/db+PTN group in 12 weeks old was significantly lower than the db/db group, and the degree of fatty liver was significantly relieved. Conclusions PTN can reduce the inflammatory reaction, alleviate insulin resistance, and improve fat liver and prognosis of early diabetic nephropathy.

Key words: Keywords:diabetic nephropathy, insulin resistance, chronic inflammation, sesquiterpene lactones

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