Effects of Shenxiao Jiedu Tongluo Recipe on AIM2-mediated pyroptosis of renal cells in a golden hamster model of diabetic nephropathy
10.3969/j.issn.1001-1528.2024.11.010
- VernacularTitle:肾消解毒通络方对糖尿病肾病金黄地鼠肾脏AIM2介导细胞焦亡的影响
- Author:
Yu-Peng XIAO
1
;
Ying-Jun DING
;
Bao-Zhu DING
;
Shu-Jie HOU
;
Si-Yang LIU
;
Zi-Wei ZHANG
;
Xiao-Xia LI
;
Wen-Jie LIANG
;
Nan ZHANG
Author Information
1. 河北中医学院中西医结合学院,河北省中西医结合肝肾病证研究重点实验室,河北 石家庄 050200
- Keywords:
Shenxiao Jiedu Tongluo Recipe;
diabetic nephropathy;
absent in melanoma 2(AIM2);
pyroptosis;
inflammation
- From:
Chinese Traditional Patent Medicine
2024;46(11):3603-3612
- CountryChina
- Language:Chinese
-
Abstract:
AIM To investigate the effects and mechanism of Shenxiao Jiedu Tongluo Recipe on renal AIM 2-mediated pyroptosis of a golden hamster model of diabetic nephropathy(DN).METHODS Fifty male golden hamsters of SPF grade were randomly divided into the control group and the model group.The golden hamsters of the model group successfully developed into DN models by feeding of high glucose and high fat diet and intraperitoneal injection of STZ were further randomly assigned into the model group,the enagliflozin group(10 mg/kg),and the low-dose and the high-dose Shenxiao Jiedu Tongluo Recipe groups(12.8,25.6 g/kg)for 8 weeks gavage of the corresponding administration.The golden hamsters had their levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,and Sur detected by automatic biochemical analyzer;their serum SOD activity and MDA level detected by biochemical method;their serum levels of IL-1β,IL-18,and TNF-α detected by ELISA method;their pathomorphological changes of kidney tissue observed by HE and PAS staining;their protein expressions of ROS and γH2AX detected by immunofluorescence or immunohistochemistry;and their renal protein expressions of AIM 2,caspase-1 and GSDMD detected by Western blot and immunohistochemistry.RESULTS Compared with the control group,the model group showed atrophic glomeruli;enlarged glomerular capsule cavity;mesangial expansion;edema and necrosis in the dilated renal tubules;increased levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.01);and decreased serum SOD activity(P＜0.01).Compared with the model group,the high-dose Shenxiao Jiedu Tongluo Recipe group and the enagliflozin group displayed improved renal histopathology,decreased levels of 24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.05,P＜0.01);and increased serum SOD activity(P＜0.01).CONCLUSION Shenxiao Jiedu Tongluo Recipe can inhibit AIM 2-mediated cell death and alleviate renal inflammatory damage in golden hamsters by inhibiting their expression of ROS-dsDNA-AIM 2 signal pathway to attain reduction of their renal ROS level,DNA damage of renal intrinsic cells,and synthesis of AIM 2 inflammatory corpuscles as well.
