Effect and Mechanism of Sishenjian on Synovial Lesions in Knee Osteoarthritis Rats
10.13422/j.cnki.syfjx.20240506
- VernacularTitle:四神煎对膝骨关节炎大鼠滑膜病变的影响及机制
- Author:
Zixuan HU
1
;
Xuejun HUANG
1
;
Nan YAO
1
;
Sha PENG
1
;
Dan'e HUANG
1
;
Tao JIANG
1
;
Haining GAN
1
;
Xiaodan HUANG
1
Author Information
1. Guangdong Provincial Second Hospital of Traditional Chinese Medicine(TCM), Guangdong Provincial Engineering Technology Research Institute of TCM,The Fifth Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510095,China
- Publication Type:Journal Article
- Keywords:
Sishenjian;
synovitis;
angiogenesis;
synovial fibrosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(11):18-26
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate (MIA) in rats with knee osteoarthritis (KOA). MethodSixty female Sprague-Dawley (SD) rats were randomly divided into the following six groups: normal group, model group, celecoxib group, and high-, medium-, and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib (18 mg·kg-1) and Sishenjian (14.4, 7.2, 3.6 g·kg-1) were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured, and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin (HE) staining and picrosirius red staining. Immunohistochemistry (IHC) was used to detect the expression of vascular endothelial growth factor A (VEGFA) in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group, the transverse diameter of the knee joint in the model group significantly increased (P<0.01). Compared with the model group, the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased (P<0.01). Compared with the normal group, the expression levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the knee joint synovial fluid of model group significantly increased (P<0.01). Compared with the model group, the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased (P<0.01). Compared with the normal group, the expression levels of TGF-β1, Smad2/3, phosphorylation(p)-Smad2/3, type Ⅰ collagen α1 (ColⅠα1), type Ⅲ collagen α1 (ColⅢα1), VEGFA proteins and TGF-β1, Smad2/3, ColⅠα1, ColⅢα1 mRNA in knee joint synovium of model group significantly increased (P<0.01). Compared with the model group, the expression levels of TGF-β1, Smad2/3, phosphorylation (p)-Smad2/3, ColⅠα1, ColⅢα1, VEGFA proteins and TGF-β1, Smad2/3, ColⅠα1, ColⅢα1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased (P<0.05, P<0.01). ConclusionSishenjian can inhibit synovial inflammation and angiogenesis, and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β1/Smad2/3 pathway.