| 叶玉燕.基于AMPK/mToR自噬信号通路研究达格列净对糖尿病肾病大鼠肾损伤改善的作用机制[J].浙江中西医结合杂志,2024,34(10): |
| 基于AMPK/mToR自噬信号通路研究达格列净对糖尿病肾病大鼠肾损伤改善的作用机制 |
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| 投稿时间：2024-03-29 修订日期：2024-09-10 |
| DOI： |
| 中文关键词: 达格列净 糖尿病肾病大鼠 AMPK/mToR自噬信号通路 免疫组化 |
| 英文关键词: |
| 基金项目:浙江省公益类金华市科学技术研究计划项目(2021-4-067) |
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| 中文摘要: |
| 目的 研究达格列净在糖尿病肾病(diabetic nephropathy,DN)大鼠肾损伤改善的作用机制。方法 40只清洁级Wistar雄性大鼠按随机数字表分为空白对照组(蒸馏水灌胃)、模型组(蒸馏水灌胃)、达格列净低剂量组(达格列净1mg.kg-1.d-1)灌胃)、达格列净高剂量组(达格列净10mg.kg-1.d-1)灌胃)各10只,干预12周,观察各组大鼠体质量、24h尿量、24h尿蛋白、尿素氮(BUN)、肌酐(Scr)的差异性；比较各组病理结果；免疫组化检测各组大鼠肾组织AMPK及mTOR蛋白表达；qRT-PCR检测肾组织AMPK、mTOR mRNA表达。结果 空白对照组、达格列净高剂量组、达格列净低剂量组、模型组体质量依次降低,24h尿量、随机血糖、24h尿蛋白、BUN、Scr依次升高。任意组间差异均有统计学意义(P<0.05)；模型组、达格列净低剂量组与达格列净高剂量组病理结果比较,肾小球大小逐渐恢复,细胞排列依次紧密有序,肾小管上皮细胞空泡样变性逐渐减小,细胞排列整齐度依次增加,出血减少。免疫组化:P-AMPK棕黄色颗粒状阳性反应物:空白对照组(++++)、模型组(+),达格列净低剂量组(++),达格列净高剂量组(+++)；P-mTOR棕黄色颗粒状阳性反应物:空白对照组(+)、模型组肾小管(++++)、达格列净低剂量组(+++)、达格列净高剂量组(++)；空白对照组、达格列净高剂量组、达格列净低剂量组、模型组AMPK蛋白、mRNA依次降低,mTOR蛋白、mRNA表达依次增加,任意组间差异均有统计学意义(P<0.05)。结论 达格列净可激活AMPK/m TOR自噬信号通路,保护肾小球的滤过屏障,减少蛋白尿的发生,延缓大鼠的糖尿病肾病进程。 |
| 英文摘要: |
| Objective To investigate the mechanism of dapagliflozin in the improvement of kidney injury in rats with diabetic nephropathy (DN). Methods? A total of 40 clean-grade Wistar male rats were divided into blank control group (distilled water gavage), model group (distilled water gavage), dapagliflozin low-dose group (dapagliflozin 1mg.kg-1.d-1) gavage), and dapagliflozin high-dose group (dapagliflozin 10mg.kg-1.d-1) gavage) according to the random number table, and the body weight, 24-hour urine output, 24-hour urine protein, urea nitrogen (BUN), and body weight, 24-hour urine output, 24-hour urine protein, urea nitrogen (BUN) were observed in each group. Differences in creatinine (Scr), pathological results were compared among the groups, immunohistochemistry was used to detect the expression of AMPK and mTOR protein in kidney tissue, and qRT-PCR was used to detect the expression of AMPK and mTOR mRNA in kidney tissue.Results The body weight of the blank control group, dapagliflozin high-dose group, dapagliflozin low-dose group, and model group decreased sequentially, and the 24-hour urine output, random blood glucose, 24-hour urine protein, BUN, and Scr increased sequentially. There were statistically significant differences between any groups (P<0.05). Compared with the pathological results of the model group, the low-dose dapagliflozin group and the high-dose dapagliflozin group, the glomerular size gradually recovered, the cell arrangement was tight and orderly, the vacuolar degeneration of renal tubular epithelial cells gradually decreased, the uniformity of cell arrangement increased, and the bleeding decreased. Immunohistochemistry: P-AMPK brownish-yellow granular positive reactants: blank control group (++++), model group (+), dapagliflozin low-dose group (++), dapagliflozin high-dose group (+++); P-mTOR brown-yellow granular positive reactants: blank control group (+), model group renal tubule (++++), dapagliflozin low-dose group (+++), dapagliflozin high-dose group (++); The AMPK protein and mRNA decreased in the blank control group, dapagliflozin high-dose group, dapagliflozin low-dose group, and model group, and the mTOR protein and mRNA expressions increased sequentially, and the differences between any group were statistically significant(P<0.05). Conclusion Dapagliflozin can activate the AMPK/m TOR autophagy signaling pathway, protect the glomerular filtration barrier, reduce the occurrence of proteinuria, and delay the progression of diabetic nephropathy in rats. |
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