Therapeutic Effect of Tongluo Jiedu Xiezhuo Prescription on Gouty Arthritis by Regulating Formation and Release of NETs
10.13422/j.cnki.syfjx.20240640
- VernacularTitle:通络解毒泄浊方通过调控中性粒细胞外诱捕网的形成与释放对痛风性关节炎的治疗作用
- Author:
Tingting LIU
1
;
Shumin LIU
1
;
Chunmiao YU
1
;
Yu WANG
1
;
Donghua YU
1
Author Information
1. Institute of Traditional Chinese Medicine， School of Pharmacy， Heilongjiang University of Chinese Medicine， Harbin 150040， China
- Publication Type:Journal Article
- Keywords:
Tongluo Jiedu Xiezhuo prescription;
gouty arthritis;
neutrophil extracellular traps;
inflammatory response;
inflammatory infiltration
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(19):73-80
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of Tongluo Jiedu Xiezhuo prescription （TLJDXZ） on alleviating inflammatory response in rats with gouty arthritis （GA） by regulating the formation and release of neutrophil extracellular traps （NETs）. MethodOxonic acid potassium salt solution combined with uric acid sodium solution was used to establish the GA rat model by injection. Seventy-two SD rats were randomly divided into control model， model group， and low-， medium-， and high-dose （1.58， 3.15， and 6.30 g∙kg-1） TLJDXZ groups， and colchicine group （0.30 mg∙kg-1）. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to characterize the chemical components of TLJDXZ. HE staining was used to observe the ankle joint tissue structure of rats. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of inflammatory factors interleukin （IL）-1β， IL-6，IL-8， blood uric acid （BUA） tumor necrosis factor （TNF）-α， reactive oxygen species （ROS）， and myeloperoxidase （MPO） in serum and tissue. PicoGreen staining method was used to measure ds-DNA concentration in plasma. Western blot was used to detect the expression of citrullinated histone H3 （Cit-H3） and MPO proteins. Immunofluorescence was used to detect the expression of neutrophil elastase （NE） and MPO. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect peptidylarginine deiminase 4 （PAD4） mRNA expression. ResultCompared with control group， the model group had severe joint swelling， with shed cell debris， synovial and connective tissue proliferation， and inflammatory cell punctate infiltration visible in the joint cavity. Blood circulation， oxidative damage， and inflammation in joint tissues significantly worsened （P<0.05）. The expression of NETs-related proteins Cit-H3， MPO， NE， and PAD4 was significantly upregulated （P<0.05）. Compared with the results in model group， joint damage in the TLJDXZ groups was significantly reduced， and the swelling was alleviated. The inflammatory infiltration in the joint cavity， cartilage and synovial morphology， and joint structure were significantly relieved. TLJDXZ significantly reduced oxidative damage and inflammation in peripheral blood circulation and joint tissues （P<0.05）. The expression of NETs-related proteins Cit-H3， MPO， NE， and PAD4 was significantly downregulated （P<0.05）. ConclusionTLJDXZ can effectively alleviate joint inflammatory response in GA rats， and its mechanism of action may be related to the regulation of the formation and release of NETs.
