Effect of Yiqi Yangyin Huoxue Prescription on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway in Diabetic Kidney Disease Rats
10.13422/j.cnki.syfjx.20221945
- VernacularTitle:益气养阴活血方对糖尿病肾病大鼠NLRP3/Caspase-1/GSDMD细胞焦亡通路的影响
- Author:
Pingping JIA
1
;
Chundong SONG
1
;
Fengyang DUAN
1
;
Ningli WANG
1
;
Ying DING
1
;
Yaoxian WANG
2
;
Xianqing REN
1
;
Wensheng ZHAI
1
Author Information
1. Department of Pediatrics， The First Affiliated Hospital of Henan University of Traditional Chinese Medicine，Zhengzhou 450000，China
2. Beijing University of Chinese Medicine，Beijing 100029，China
- Publication Type:Journal Article
- Keywords:
Yiqi Yangyin Huoxue prescription;
diabetic kidney disease;
pyroptosis;
NOD-like receptor protein 3（NLRP3）;
cysteine protease-1（Caspase-1）;
gasdermin D（GSDMD）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(1):75-81
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the possible mechanism of Yiqi Yangyin Huoxue prescription in the prevention and treatment of kidney injury of diabetic kidney disease（DKD）rats based on NOD-like receptor protein 3（NLRP3）/cysteine protease-1（Caspase-1）/gasdermin D （GSDMD）pyroptosis pathway. MethodFifty male SD rats were randomly divided into normal group （n=8） and modeling group （n=42）. The modeling group was given a one-time intraperitoneal injection of streptozotocin （STZ） after high-sugar and high-fat diet for 6 weeks to induce the establishment of a DKD rat model. After successful modeling， the rats were randomly divided into model group， valsartan group （8.33 mg·kg-1）， and Yiqi Yangyin Huoxue prescription low-dose and high-dose group （11，22 g·kg-1）. After continuous gavage for 6 weeks， the fasting blood glucose （FBG）， total cholesterol （CHO）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （SCr） and 24-hour urine protein quantification （24 h-UTP） were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of kidney tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin-1β （IL-1β） and interleukin-18 （IL-18） levels. The protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue of rats in each group were determined by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in normal group， the levels of FBG， CHO， TG， BUN， SCr， 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in model group were increased （P<0.01）， and the kidney tissue lesions were severe. Compared with the conditions in model group， the levels of FBG， CHO， TG， BUN， SCr， 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in each intervention group were decreased （P<0.05， P<0.01）， and the degree of kidney tissue lesions was improved， with Yiqi Yangyin Huoxue prescription high-dose group showing the optimal effect. ConclusionYiqi Yangyin Huoxue prescription could inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway， and thus relieve the inflammatory response of DKD rats and alleviate the pathological damage of the kidneys.
