Mechanism of Huayu jiedu formula in alleviating inflammatory injury in chronic kidney disease based on AIM2 pyroptosis pathway
- VernacularTitle:基于AIM2焦亡途径探讨化瘀解毒方减轻慢性肾脏病炎性损伤的作用机制
- Author:
Jinhuan XUE
1
;
Ziwen WU
1
;
Fan YANG
1
;
Yunyun LOU
1
;
Yingjun DING
1
;
Yupeng XIAO
2
;
Xianhui LIU
1
;
Wenjie LIANG
1
Author Information
1. Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Hepatorenal Diseases，Hebei University of Chinese Medicine，Shijiazhuang 050200，China
2. Dept. of Traditional Chinese Medicine Pediatrics，Hebei Children’s Hospital，Shijiazhuang 050031，China
- Publication Type:Journal Article
- Keywords:
chronic kidney disease;
Huayu jiedu formula;
absent in melanoma 2;
pyroptosis pathway
- From:
China Pharmacy
2025;36(21):2638-2644
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease （CKD）. METHODS Fifty male SD rats were randomly divided into a sham surgery group （10 rats） and a modeling group （40 rats）. The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling， the rats were randomly divided into model group， esaxerenone group （positive control）， and TCM low- and high-dose groups， with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone， while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively， the sham surgery group and model group were given an equal volume of physiological saline， all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea （SUr）， serum creatinine （SCr）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels； enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α（TNF-α）； immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α） ， mitochondrial transcription factor A （TFAM）， absent in melanoma 2（AIM2）， caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in renal tissue； real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group， the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction， severe tubular dilation， and increased deposition of blue fibrin； the levels of SUr， SCr， MDA， IL-1β， IL-6， TNF-α，the protein expression of AIM2， GSDMD， caspase-1， IL-1β， IL-18 ， and the mRNA expression of AIM2 were significantly increased or up-regulated （P＜0.01）； the levels of SOD， the protein expression of PGC-1α， TFAM were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function， alleviate renal inflammatory damage and pyroptosis， and exert renal protective effects by regulating the AIM2 pyroptosis pathway.
