Qingre Sanzhuo Decoction Treats Gouty Arthritis Combined with Hyperuricaemia in Rats via NLRP3/ASC/Caspase-1 Pathway
10.13422/j.cnki.syfjx.20241137
- VernacularTitle:基于NLRP3/ASC/Caspase-1途径探讨清热散浊饮对痛风性关节炎合并高尿酸血症模型大鼠的作用机制
- Author:
Haolin LI
1
;
Qian BAI
1
;
Weigang CHENG
1
;
Weiqing LI
2
;
Juanjuan YANG
1
;
Peixin HE
1
;
Huijun YANG
2
;
Haidong WANG
2
Author Information
1. Gansu University of Chinese Medicine， Lanzhou 730000， China
2. Gansu Provincial Hospital of Traditional Chinese Medicine， Lanzhou 730050， China
- Publication Type:Journal Article
- Keywords:
Qingre Sanzhuo decoction;
NOD-like receptor protein 3 （NLRP3）/apoptosis-associated speck-like protein containing CARD （ASC）/cysteinyl aspartate-specific protease 1 （Caspase-1） pathway;
gouty arthritis;
hyperuricaemia
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(3):49-57
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.
