芒柄花苷经AMPK/SIRT1/FoxO1通路对2型糖尿病肾病大鼠肾损伤的改善作用

doi:10.3969/j.issn.1006-6233.2022.11.05

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摘要 目的: 探讨芒柄花苷经AMPK/SIRT1/FoxO1通路对2型糖尿病肾病(DN)大鼠肾损伤的改善作用。方法: 用腹腔注射链脲佐菌素准备大鼠DN模型,芒柄花苷低剂量组和芒柄花苷高剂量组大鼠分别灌胃给予芒柄花苷(剂量分别为50mg/kg和200mg/kg),阳性对照组灌胃给予二甲双胍(250mg/kg),阴性对照组和模型组灌胃给予等量生理盐水,持续16周。测定大鼠血清中BUN、Scr和血糖水平,对大鼠肾脏进行病理学检查,同时采用Western Blot法检测肾组织中SOD、GSH-PX、MDA、AMPK、SIRT1、FoxO1、FN和LC3B蛋白水平。结果: 模型组大鼠肾小球异常肥大,系膜细胞增殖,系膜基质增加,间质纤维化;芒柄花苷和二甲双胍治疗后,肾小球形态逐渐恢复正常,肾小球内的炎症和纤维化程度也有不同程度的改善。与阴性对照组比较,模型组、芒柄花苷低剂量组、芒柄花苷高剂量组和阳性对照组各组大鼠BUN、Scr、血糖、MDA、FoxO1和FN水平升高,SOD、GSH-PX、AMPK、SIRT1和LC3B水平降低(P<0.05)。与模型组比较,芒柄花苷低剂量组、芒柄花苷高剂量组和阳性对照组大鼠BUN、Scr、血糖、MDA、FoxO1和FN水平降低,SOD、GSH-PX、AMPK、SIRT1和LC3B水平升高(P<0.05)。与芒柄花苷低剂量组比较,芒柄花苷高剂量组和阳性对照组大鼠BUN、Scr、血糖、MDA、FoxO1和FN水平降低,SOD、GSH-PX、AMPK、SIRT1和LC3B水平升高(P<0.05)。芒柄花苷高剂量组和阳性对照组各指标差异无统计学意义(P>0.05)。结论: 芒柄花苷对2型糖尿病肾病大鼠肾损伤具有明显的改善作用,其机制可能是与芒柄花苷激活AMPK/SIRT1/FoxO1通路有关。

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	姚艺
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关键词 ：芒柄花苷, AMPK/SIRT1/FoxO1通路, 2型糖尿病, 糖尿病肾病, 肾损伤

Abstract：Objective: To investigate the ameliorating effect of Ononin on renal injury in rats with type 2 diabetic nephropathy via AMPK/SIRT1/FoxO1 pathway.Methods: The DN model of rat was prepared by intraperitoneal injection of streptozotocin. The rats in the low-dose Ononin group and the high-dose Ononin group were given Ononin by gavage (the doses were 50mg/kg and 200mg/kg, respectively), and the positive control group was given metformin (250mg/kg) by gavage, and the negative control group and model group were given the same amount of normal saline by gavage for 16 weeks. The serum levels of BUN, Scr and blood sugar were measured, and pathological examinations of rat kidneys were performed. At the same time, Western Blot method was used to detect the protein levels of SOD, GSH-PX, MDA, AMPK, SIRT1, FoxO1, FN and LC3B in kidney tissue.Results: In the model group, the glomerulus was abnormally enlarged, the mesangial cells proliferated, the mesangial matrix increased, and the interstitial fibrosis. After Ononin and metformin treatment, the glomerular morphology gradually returned to normal, The degree of inflammation and fibrosis transformation in the glomerulus were also improved in varying degrees. Compared with the negative control group, the levels of BUN, Scr, blood sugar, MDA, FoxO1 and FN in the model group, Ononin low-dose group, Ononin high-dose group and positive control group increased, SOD, GSH -PX, AMPK, SIRT1 and LC3B levels decreased(P<0.05). Compared with the model group, the levels of BUN, Scr, blood sugar, MDA, FoxO1 and FN in the low-dose Ononin group, high-dose Ononin group and the positive control group decreased, and SOD, GSH-PX, AMPK, SIRT1 and LC3B increased(P<0.05). Compared with the low-dose Ononin group, the levels of BUN, Scr, blood glucose, MDA, FoxO1 and FN in the high-dose Ononin group and the positive control group decreased, and the levels of SOD, GSH-PX, AMPK, SIRT1 and LC3B increased(P<0.05). There was no significant difference in indexes between the high-dose Ononin group and the positive control group(P>0.05). Conclusion: Ononin has a significant improvement effect on kidney injury in rats with type 2 diabetic nephropathy, and its mechanism may be related to the activation of AMPK/SIRT1/FoxO1 pathway by Ononin.

Key words： Ononin AMPK/SIRT1/FoxO1 pathway Type 2 diabetes Diabetic nephropathy Kidney injury

基金资助:湖北省卫生健康委员会项目,(编号:WJ2021F038)

通讯作者: 陈思思

引用本文:

姚艺, 李艳丽, 丁洪成, 陈思思. 芒柄花苷经AMPK/SIRT1/FoxO1通路对2型糖尿病肾病大鼠肾损伤的改善作用[J]. 河北医学, 2022, 28(11): 1785-1789.
YAO Yi, LI Yanli, DING Hongcheng, et al. The Ameliorating Effect of Ononin on Renal Injury in Rats with Type 2 Diabetic Nephropathy via AMPK/SIRT1/FoxO1 Pathway. HeBei Med, 2022, 28(11): 1785-1789.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2022.11.05 或 http://www.hbyxzzs.cn/CN/Y2022/V28/I11/1785

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