The Mechanism of Jianpi Gushen Huayu Decoction (健脾固肾化瘀方) in the Treatment of Diabetic Kidney Disease Based on SIRT6/NRF2 Pathway

Author：LIU Zhen, DONG Li, CHEN Xiaoting, ZHANG Hui, PAN Baochao, SU Xiuhai, WANG Qinghai, LYU Shuquan

Unit：Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province, Cangzhou Hebei 061000, China

Quote：引用：刘珍，董礼，陈晓婷，张辉，潘保朝，苏秀海，王庆海，吕树泉.基于SIRT6/NRF2通路研究健脾固肾化瘀方治疗糖尿病肾脏病的机制[J].中医药导报,2025,31(1):32-36,41.

DOI：10.13862/j.cn43-1446/r.2025.01.006

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Abstract：

Objective: To evaluate the effect of Jianpi Gushen Huayu decoction (JPGS) in the treatment of diabetic kidney disease and to explore the mechanism from the oxidative stress and inflammatory mediated by sirtuin-6 (SIRT6)/ nuclear factor-erythroid 2 related factor 2 (NRF2) pathway. Methods: After one week of adaptive feeding, 60 C57BL/6J mice were randomly divided into normal group (n=50) and modeling group (n=50). Rats were given maintenance feed in normal group, while carbohydrate and high fat diet (HFD) in modeling group for 8 weeks. After 8 weeks, mice in modeling group were received intraperitoneal injection of STZ for modeling. The successfully modeled mice were randomly divided into model group, SIRT6 agonist group, low-dose JPGS group, medium-dose JPGS group, and high-dose JPGS group, 10 mice in each group. Kit was used to determine 24-h urine protein quantification (24 h-UPQ), serum creatinine (Cr) and urea nitrogen (BUN) in mice. Hematoxylin-eosin and Masson staining were performed on the same part of the kidney. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), IL-1β, IL-6 and TNF-α in kidney tissue were measured by kits. Western blotting was used to detect the expression of SIRT6/NRF2 pathway-related factors [SIRT6, NRF2, HO-1, GCLC, NQO1], and RT-qPCR was used to detect the expression of GCLC mRNA, NQO1 mRNA, SOD1 mRNA, and GPX1 mRNA. Results: JPGS reduced Cr, BUN, 24h-UPQ, attenuated renal histopathological injury, decreased MDA and ROS levels, enhanced SOD and GSH-Px activities, lowered IL-1β, IL-6, and TNF-α levels, elevated the expression levels of SIRT6, NRF2, HO-1, GCLC, and NQO1, and increased expression of GCLC mRNA, NQO1 mRNA, SOD1 mRNA and GPX1 mRNA in mice of diabetic kidney disease. Conclusion: JPGS can inhibit oxidative stress and inflammatory by activating SIRT6/NRF2 pathway to alleviate DKD kidney injury.

Key words：diabetic kidney disease; Jianpi Gushen Huayu decoction; oxidative stress; inflammatory; SIRT6; NRF2

摘要：目的：研究健脾固肾化瘀方（JPGS）治疗糖尿病肾脏病的效果并从沉默调节蛋白6（SIRT6）/核因子类红细胞相关因子2（NRF2）通路介导的氧化应激与炎症反应研究JPGS治疗糖尿病肾脏病的作用机制。方法：60只C57BL/6J小鼠适应性喂养1周后，随机分为正常组（n=50）及造模组（n=50）。正常组小鼠给予正常小鼠维持饲料，造模组小鼠高糖高脂饮食喂养8周。8周后，造模组小鼠腹腔注射STZ进行造模。模型成功的小鼠随机分为模型组、SIRT6激动剂组、JPGS低剂量组、JPGS中剂量组及JPGS高剂量组，每组10只。采用试剂盒测定小鼠24 h尿蛋白定量，血清肌酐、尿素氮。对肾脏同一部位进行苏木素-伊红、Masson染色。采用试剂盒测定小鼠肾组织丙二醛水平，超氧化物歧化酶和谷胱甘肽过氧化物酶活性、活性氧水平、白细胞介素-1β、IL-6、肿瘤坏死因子-α水平。采用Western blotting检测SIRT6/NRF2通路相关因子[SIRT6、NRF2、血红素氧合酶-1、谷氨酸半胱氨酸连接酶催化亚基、NAD(P)H醌氧化还原酶1]表达，采用RT-qPCR检测GCLC mRNA、NQO1 mRNA、SOD1 mRNA、GPX1 mRNA表达。结果：JPGS能降低糖尿病肾脏病小鼠的Cr、BUN、24 h-UPQ，减轻肾组织病理损伤，降低MDA、ROS水平，增强SOD、GSH-PX活性，降低IL-1β、IL-6、TNF-α水平，升高SIRT6、NRF2、HO-1、GCLC、NQO1表达水平，升高GCLC mRNA、NQO1 mRNA、SOD1 mRNA及GPX1 mRNA的表达。结论：JPGS可以激活SIRT6/NRF2通路抑制氧化应激与炎症反应以缓解糖尿病肾脏病的肾损伤。

关键词：糖尿病肾脏病；健脾固肾化瘀方；氧化应激；炎症；SIRT6；NRF2

Release time：2025-11-28

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