醋酸泼尼松对糖尿病肾病模型大鼠肾功能、肾脏炎性反应及AMPK/SIRT1信号通路的影响

doi:10.16352/j.issn.1001-6325.2022.02.006

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (2): 243-248.doi: 10.16352/j.issn.1001-6325.2022.02.006

醋酸泼尼松对糖尿病肾病模型大鼠肾功能、肾脏炎性反应及AMPK/SIRT1信号通路的影响

邓九红^1,2, 郑超^1*, 王声遥¹, 王心怡¹

1.温州医科大学第二临床医学院, 浙江温州 325035;
2.平阳县第二人民医院内分泌科,浙江平阳 325405

收稿日期:2021-09-13 修回日期:2021-12-08 出版日期:2022-02-05 发布日期:2022-01-24
通讯作者: ^* chao_zheng@zju.edu.cn
基金资助:
浙江省科技计划项目(2021C03070)

Effects of prednisone acetate on renal function, renal inflammation and AMPK/SIRT1 signaling pathway in diabetic nephropathy rats

DENG Jiu-hong^1,2, ZHENG Chao^1*, WANG Sheng-yao¹, WANG Xin-yi¹

1. the Second Clinical Medical College, Wenzhou Medical University, Wenzhou 325035;
2. Department of Endocrinology, the Second People's Hospital of Pingyang County, Pingyang 325405, China

Received:2021-09-13 Revised:2021-12-08 Online:2022-02-05 Published:2022-01-24
Contact: ^* chao_zheng@zju.edu.cn

摘要/Abstract

摘要： 目的探究醋酸泼尼松对糖尿病肾病(DN)大鼠肾脏炎性反应及腺苷酸活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)信号通路的影响。方法随机选取12只大鼠作为对照组,将其余大鼠用高糖高脂饲料辅以腹腔注射链脲佐菌素(STZ)构建DN大鼠模型。将造模成功大鼠随机分为模型组、醋酸泼尼松低(6.25 mg/kg)、高(12.5 mg/kg)剂量组、醋酸泼尼松+CC组(醋酸泼尼松12.5 mg/kg+AMPK抑制剂compound C 0.2 mg/kg),每组12只。各组给予相应处理,1次/d,共给药4周。观察大鼠一般状态,检测空腹血糖(FBG)、24 h尿微量白蛋白(U-mAlb)、血肌酐(SCr)、血尿素氮(BUN)、血清白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平;苏木精-伊红(HE)和高碘酸-希夫(PAS)染色观察肾脏组织病理形态学变化;蛋白免疫印迹法检测肾组织AMPK/SIRT1信号通路相关蛋白的表达。结果醋酸泼尼松可改善DN大鼠一般状态,降低FBG、24 h U-mAlb、血清SCr、BUN、IL-1β、IL-6和TNF-α水平、肾组织乙酰化核因子-κB p65(ac-NF-κB p65)/NF-κB p65和单核细胞趋化蛋白-1(MCP-1)蛋白表达(P＜0.05),升高磷酸化AMPK(p-AMPK)/AMPK、SIRT1蛋白表达(P＜0.05),改善肾脏病变;compound C可明显减弱醋酸泼尼松对DN大鼠的保护作用。结论醋酸泼尼松可减轻DN大鼠肾脏炎性反应,保护肾功能,其作用机制可能与激活AMPK/SIRT1通路,进而抑制NF-κB激活有关。

关键词: 醋酸泼尼松, 糖尿病肾病, 炎性反应, 腺苷酸活化蛋白激酶/沉默信息调节因子1信号通路(AMPK/SIRT1)

Abstract: Objective To explore the effect of prednisone acetate on renal function, renal inflammatory response and AMP-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) signaling pathway in diabetic nephropathy (DN) rats. Methods Twelve rats were randomly selected as the control group, and the remaining rats were given high-sugar and high-fat diet supplemented with intraperitoneal injection of streptozotocin (STZ) to construct a DN rat model. The successful model rats were randomly divided into model group, prednisone acetate low (6.25 mg/kg), high (12.5 mg/kg) dose groups, prednisone acetate + CC group (prednisone acetate 12.5 mg/kg+AMPK inhibitor compound C 0.2 mg/kg), with 12 animals in each group. Each group was given corresponding treatment, once a day for 4 weeks. The general state of rats was observed, and the fasting blood glucose (FBG), 24-hour urine microalbumin (U-mAlb), blood creatinine (SCr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected; the pathological changes of renal tissue were observed with hematoxylin eosin (HE) staining and periodate schiff (PAS) staining; The expression of proteins related to the renal tissue AMPK/SIRT1 signaling pathway was detected with Western blot. Results Prednisone acetate can improve the general state of DN rats, reduce FBG, 24 h U-mAlb, serum SCr, BUN, IL-1β, IL-6 and TNF-α levels, and renal tissue acetylation nuclear factor-κB p65 (ac-NF-κB p65)/NF-κB p65 and monocyte chemotactic protein-1 (MCP-1) protein expression (P＜0.05), increase phosphorylated AMPK(p-AMPK)/AMPK and SIRT1 protein expression (P＜0.05), improve kidney disease; compound C could significantly weaken the protective effect of prednisone acetate on DN rats. Conclusions Prednisone acetate can reduce renal inflammatory response and protect renal function in DN rats. Its mechanism may be related to the activation of AMPK/SIRT1 pathway to inhibit the activation of NF-κB.

Key words: prednisone acetate, diabetic nephropathy, inflammatory reaction, AMP-activated protein kinase/silent information regulator 1 signaling pathway(AMPK/SIRT1)

中图分类号:

邓九红, 郑超, 王声遥, 王心怡. 醋酸泼尼松对糖尿病肾病模型大鼠肾功能、肾脏炎性反应及AMPK/SIRT1信号通路的影响[J]. 基础医学与临床, 2022, 42(2): 243-248.

DENG Jiu-hong, ZHENG Chao, WANG Sheng-yao, WANG Xin-yi. Effects of prednisone acetate on renal function, renal inflammation and AMPK/SIRT1 signaling pathway in diabetic nephropathy rats[J]. Basic & Clinical Medicine, 2022, 42(2): 243-248.

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醋酸泼尼松对糖尿病肾病模型大鼠肾功能、肾脏炎性反应及AMPK/SIRT1信号通路的影响

Effects of prednisone acetate on renal function, renal inflammation and AMPK/SIRT1 signaling pathway in diabetic nephropathy rats

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