| 宋 丹,陈远珍,蒋 英,李 萍,谭桂平,黄连方.丁酸钠通过调节SIRT1/AMPK信号通路对慢性肾衰竭大鼠肾功能的影响[J].现代生物医学进展英文版,2023,(7):1218-1224. |
| 丁酸钠通过调节SIRT1/AMPK信号通路对慢性肾衰竭大鼠肾功能的影响 |
| Effect of Sodium Butyrate on Renal Function in Rats with Chronic Renal Failure by Regulating SIRT1/AMPK Signal Pathway |
| Received:November 27, 2022 Revised:December 23, 2022 |
| DOI：10.13241/j.cnki.pmb.2023.07.004 |
| 中文关键词: 丁酸钠 SIRT1/AMPK 慢性肾衰竭 大鼠 肾功能 |
| 英文关键词: Sodium butyrate SIRT1/AMPK Chronic renal failure Rats Renal function |
| 基金项目:深圳市光明区卫生健康局2018-2019年度中医药科研项目（GM2019020016）；广东省医学科学技术研究基金项目（B20180697） |
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| 中文摘要: |
| 摘要 目的：探讨丁酸钠（NaB）通过调节沉默信息调节因子1（SIRT1）/单磷酸腺苷活化蛋白激酶（AMPK）信号通路对慢性肾衰竭（CRF）大鼠肾功能的影响。方法：选用SD大鼠72只，随机分为6组（12只/组）：control组、Model组、NaB低剂量组（100 mg/kg）、NaB中剂量组（200 mg/kg）、NaB高剂量组（400 mg/kg）、抑制剂组（400 mg/kg NaB+2 mg/kg SIRT1/AMPK通路抑制剂EX527）；采用饲喂0.5%腺嘌呤饲料以建立CRF大鼠模型，建模成功后，灌胃和腹腔注射相应药物。使用试剂盒检测大鼠24 h尿蛋白（24 h U-pro）、血清肌酐（SCr）、尿素氮（BUN）水平；采用苏木精-伊红（HE）及Masson染色法观察肾脏病理改变，并计算胶原容积分数（CVF）；采用茜素红染色法与主动脉钙含量测定评估主动脉钙化情况；采用酶联免疫吸附法（ELISA）检测各组大鼠肾脏组织白细胞介素（IL）-6、IL-β、肿瘤坏死因子（TNF）-α水平；采用过氧化氢酶（CAT）、丙二醛（MDA）、活性氧（ROS）检测试剂盒检测大鼠肾脏组织中CAT、MDA、ROS水平；采用蛋白免疫印迹法（WB）检测各组大鼠SIRT1/AMPK信号通路及骨形态发生蛋白2（BMP2）、Runt相关转录因子2（Runx2）蛋白的表达。结果：与control组比较，Model组大鼠肾脏组织损伤严重、胶原纤维沉积显著、主动脉钙化严重，CAT活性、SIRT1、p-AMPK/AMPK表达水平显著降低（P<0.05），CVF、主动脉钙含量和SCr、BUN、24 h U-pro、IL-6、IL-β、TNF-α、MDA、ROS水平及BMP2、Runx2蛋白表达水平显著升高（P<0.05）；与Model组比较，NaB低、中、高剂量组大鼠肾脏组织损伤减轻、胶原纤维沉积面积明显减少、主动脉钙化程度减轻，CVF、主动脉钙含量和SCr、BUN、24 h U-pro、IL-6、IL-β、TNF-α、MDA、ROS水平及BMP2、Runx2蛋白表达水平显著降低（P<0.05），CAT活性、SIRT1、p-AMPK/AMPK表达水平显著升高（P<0.05）；SIRT1/AMPK通路抑制剂EX527可降低高剂量NaB对CRF大鼠主动脉钙化和肾功能的改善作用（P<0.05）。结论：NaB可能通过激活SIRT1/AMPK信号通路，减轻肾脏组织炎症、氧化应激损伤、主动脉钙化和肾纤维化，从而起到改善CRF大鼠肾功能的作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of sodium butyrate (NaB) on renal function in rats with chronic renal failure (CRF) by regulating silent information regulator 1 (SIRT1)/adenosine monophosphate activated protein kinase (AMPK) signal pathway. Methods: A total of 72 SD rats were selected, and they were randomly divided into six groups (12 rats/group): control group, Model group, low dose NaB group (100 mg/kg), medium dose NaB group (200 mg/kg), high dose NaB group (400 mg/kg), and inhibitor group (400 mg/kg NaB+2 mg/kg SIRT1/AMPK pathway inhibitor EX527). The CRF rat model was established by feeding 0.5% adenine feed, and after successful modeling, the corresponding drugs were injected by gavage and intraperitoneal injection. The levels of 24 h urine protein (24 h U-pro), serum creatinine (Scr) and blood urea nitrogen (BUN) in rats were detected with the kits. The hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes of the kidney, and the collagen volume fraction (CVF) was calculated. The alizarin red staining and aortic calcium content determination were used to evaluate aortic calcification. The levels of interleukin (IL)-6, IL-β and tumor necrosis factor-alpha (TNF-α) in kidney tissue of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA). The levels of CAT, MDA and ROS in kidney tissue of rats were detected with catalase (CAT), malondialdehyde (MDA) and reactive oxygen species (ROS) detection kits. The western blot was used to detect the expression of SIRT1/AMPK signal pathway and bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (Runx2) protein in rats in each group. Results: Compared with the control group, the kidney tissue of rats in the model group was severely damaged, collagen fiber deposition was significant, aortic calcification was serious, CAT activity, SIRT1, p-AMPK/AMPK expression levels were significantly decreased (P<0.05), while CVF, aortic calcium content and SCr, BUN, 24h U-pro, IL-6, IL-β, TNF-α, MDA, ROS and BMP2, Runx2 protein expression levels were significantly increased(P<0.05). Compared with the model group, the renal tissue damage, collagen fiber deposition area, aortic calcification, CVF, aortic calcium content, and SCr, BUN, 24h U-pro, IL-6, IL-β, TNF-α, MDA, ROS and BMP2, Runx2 protein expression levels in the low, middle, and high dose NaB groups were significantly decreased(P<0.05), while CAT activity, SIRT1, p-AMPK/AMPK expression were significantly increased(P<0.05). EX527, an inhibitor of SIRT1/AMPK pathway, could reduce the improvement of aortic calcification and renal function in CRF rats by high-dose NaB (P<0.05). Conclusion: NaB may play a role in improving the renal function of CRF rats by activating SIRT1/AMPK signal pathway and reducing renal tissue inflammation, oxidative stress injury, aortic calcification and renal fibrosis. |
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