Mechanism of Yiqi yangyin huazhuo tongluo formula in ameliorating diabetic kidney disease by regulating the gut microbiota-LPS/Caspase-11/GSDMD pathway
- VernacularTitle:益气养阴化浊通络方调控肠道菌群-LPS/Caspase-11/GSDMD通路改善糖尿病肾病的机制研究
- Author:
Zijun HOU
1
;
Yingli LI
2
;
Kelei GUO
2
;
Yiyuan WANG
3
;
Shiyu HUANG
3
;
Lujia ZHANG
3
;
Hua BIAN
3
Author Information
1. School of Nursing，Henan University of Chinese Medicine，Zhengzhou 450046，China
2. Zhang Zhongjing School of Chinese Medicine，Nanyang Institute of Technology，Henan Nanyang 473004，China;Henan Provincial Key Laboratory of Zhang Zhongjing Formulae and Immunoregulation，Nanyang Institute of Technology，Henan Nanyang 473004，China
3. Zhang Zhongjing School of Chinese Medicine，Nanyang Institute of Technology，Henan Nanyang 473004，China
- Publication Type:Journal Article
- Keywords:
Yiqi yangyin huazhuo tongluo formula;
Diabetic kidney disease;
gut microbiota;
LPS/Caspase-11/GSDMD pathway;
pyroptosis
- From:
China Pharmacy
2026;37(19):2536-2543
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mechanism of Yiqi yangyin huazhuo tongluo formula in ameliorating diabetic kidney disease （DKD） based on the gut microbiota-lipopolysaccharide （LPS）/Caspase-11/gasdermin D （GSDMD） pathway.METHODS A DKD mouse model was established by high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin. The successfully modeled mice were randomly divided into model group， metformin group （positive control， 200 mg/kg） and Yiqi yangyin huazhuo tongluo formula group （32.4 g/kg， calculated as crude drug dosage）， with 10 mice in each group； another 10 mice were set as the control group. Mice were intragastrically administered with corresponding drug solutions or normal saline once a day for 8 consecutive weeks. After the last administration， serum glycolipid metabolism indicators and urinary renal function indicators of mice were determined； the pathological and morphological changes of renal and colonic tissues were observed； LPS contents in renal tissues， colonic contents and serum were detected. 16S rRNA high-throughput sequencing was performed for gut microbiota analysis of colonic contents. The protein expressions of Occludin and zonula occludens-1 （ZO-1） in colonic tissues as well as Caspase-11 and GSDMD in renal tissues were detected.RESULTS Compared with the control group， the model group exhibited significantly elevated levels of serum fasting blood glucose， triglyceride， total cholesterol， serum creatinine， blood urea nitrogen and microalbumin， LPS contents in each sample， as well as protein expressions of Caspase-11 and GSDMD in renal tissues （ P ＜0.05）. The protein expressions of ZO-1 and Occludin in colonic tissues， together with Chao1 and Ace indices of gut microbiota， were markedly decreased （ P ＜0.05）， and the ratio of Firmicutes to Bacteroidetes was abnormally increased. Obvious histopathological changes were observed in renal and colonic tissues； the percentage of PAS-positive area in kidney was markedly increased （ P ＜0.05）. Compared with the model group， the Yiqi yangyin huazhuo tongluo formula group showed remarkable reductions in glycolipid metabolism and renal function-related indicators（except total cholesterol）， LPS contents in various samples， and renal protein expressions of Caspase-11 and GSDMD （ P ＜0.05）. The protein expression level of ZO-1 in colonic tissues and the Ace index of gut microbiota were significantly increased （ P ＜0.05）， and the relative abundance of beneficial genera including Bifidobacterium ， Faecalibaculum and Akkermansia in the gut microbiota was elevated.CONCLUSIONS The mechanism by which Yiqi yangyin huazhuo tongluo formula ameliorates DKD may be related to reshaping gut microbiota， repairing intestinal mucosal barrier， reducing LPS translocation into blood， and further inhibiting Caspase-11/GSDMD-mediated pyroptosis in kidney.
