| 刘恺远.卡格列净通过Sirt1/Claudin-1/β-catenin/Snail信号通路对糖尿病肾病小鼠模型肾脏的保护作用[J].浙江中西医结合杂志,2022,32(10): |
| 卡格列净通过Sirt1/Claudin-1/β-catenin/Snail信号通路对糖尿病肾病小鼠模型肾脏的保护作用 |
| Protective effect of canagliflozin on kidney of diabetic nephropathy mouse model through SIRT1/Claudin-1/β-catenin/snail signaling pathway |
| 投稿时间：2022-03-31 修订日期：2022-09-09 |
| DOI： |
| 中文关键词: 卡格列净 糖尿病肾脏疾病 Sirt1/Claudin1/β-catenin/Snail信号通路 |
| 英文关键词:Canagliflozin Diabetic kidney disease Sirt1/Claudin1/β-catenin/Snail signaling pathway |
| 基金项目:浙江省医药卫生科技计划项目 |
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| 中文摘要: |
| 目的：探讨卡格列净通过Sirt1/Claudin-1/β-catenin/Snail信号通路对糖尿病肾脏疾病小鼠模型肾脏的保护。方法：采用db雄性小鼠6只作为正常对照组（NC组）；SPF级2型糖尿病模型6周龄db/db雄性小鼠12只，高脂饲料完成糖尿病肾病造模，用随机表法分为糖尿病肾病组（DKD组）、糖尿病肾病+卡格列净干预组（DKD+Can组），NC组、DKD组分别予生理盐水10ml/kg，灌胃，1次/日，卡格列净干预组予10mg/（kg·d），灌胃，1次/日，共灌胃12周。末次灌胃后检测生理生化指标检测，PAS法染色观察各组小鼠肾脏组织形态。采用westren blot方法检测Sirt1、Claudin-1、β-catenin、Snail蛋白表达水平。结果：与NC组相比，DKD组Sirt1蛋白表达水平下降[（0.10±0.28）比（0.33±0.17）；P <0.01]；与DKD组相比DKD+Can组Sirt1蛋白表达水平上升[（0.24±0.01）比（0.10±0.28）；P <0.01]；Claudin-1、β-catenin、Snail表达在DKD组较NC组蛋白表达升高[Claudin-1（0.24±0.02）比（0.05±0.00）；β-catenin（0.42±0.03）比（0.08±0.00）；Snail（0.20±0.01）比（0.06±0.00）；P 均<0.01]。在DKD+Can组较DKD组降低[Claudin-1（0.12±0.01）比（0.24±0.02）；β-catenin（0.24±0.02）比（0.42±0.03）；Snail（0.15±0.01）比（0.20±0.01）；P 均<0.01]。肾小球PAS染色显示糖尿病肾病小鼠出现肾小球硬化，使用卡格列净12周后糖尿病肾病小鼠尿蛋白明显减少，肾小球硬化改善。结论：卡格列净糖尿病肾病小鼠肾脏保护机制可能通过上调Sirt1表达水平，下调Claudin-1、β-catenin、Snail表达有关。 |
| 英文摘要: |
| ABSTRACT Objective To investigate the protective effect of canagliflozin on the diabetes kidney disease mice through Sirt1/Claudin1/β-catenin/Snail signaling pathway. Methods Six male db mice were used as normal control group (NC group); Twelve 6-week-old db/db male mice with SPF type 2 diabetes mellitus were randomly divided into diabetes kidney disease group (DKD group), diabetic nephropathy+canagliflozin intervention group (DKD+Can group), NC group and DKD group were given 10ml/kg saline once a day, and canagliflozin intervention group was given 10 mg/day. After the last gastric infusion, the physiological and biochemical indexes were detected, and the renal tissue morphology of mice in each group was observed by PAS staining. The expression levels of Sirt1, Claudin-1, β-catenin and Snail protein were detected by westren blot. Results Compared with NC group, the expression level of Sirt1 protein in DKD group decreased [(0.10±0.28) vs (0.33±0.17); P <0.01]； Compared with DKD group, the expression level of Sirt1 protein in DKD+Can group increased [(0.24 ±0.01) vs (0.10±0.28); P <0.01]； The expression of Claudin-1, β-catenin and Snail in DKD group was higher than that of NC group [Claudin-1 (0.24±0.02) vs (0.05±0.00); β-catenin(0.42±0.03) vs(0.08±0.00); Snail(0.20±0.01) vs (0.06±0.00); P < 0.01]. Compared with DKD group, the express of Claudin-1, β-catenin and Snail in DKD+Can group was lower[claudin-1 (0.12±0.01) vs (0.24±0.02); β-catenin(0.24±0.02) vs (0.42±0.03); Snail(0.15±0.01) vs (0.20±0.01); P < 0.01]. Glomerular PAS staining showed that glomerulosclerosis occurred in diabetic nephropathy mice. After 12 weeks of treatment, urine protein of diabetic nephropathy mice decreased significantly, and glomerulosclerosis improved. Conclusion The mechanism of renal protection of mice with diabetic nephropathy induced by canagliflozin may be related to the up-regulation of Sirt1 expression and down-regulation of Claudin-1, β-catenin and Snail expression. |
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