Experimental Study On The Miao Traditional Medicine Jinwujiangu Decoction On The Expression Of AP-1and NF-κB In CIA Rat Synovial

Objective:By establishing the model of collagen induced arthritis (CIA) rats, observe the effects of Miao traditional medicine Jinwujiangu decoction on arthritis index (AI), joint swelling rate and joint pathological changes in CIA rats, and its’ expression of the subunit c-fos and c-jun of activator proein-1(AP-1) and the NF-κB/P65, NF-κB/P50, IκBα in nuclear transcription factors kappa B (NF-κB) signal pathway in synovial.To investigate the action mechanism of Jinwujiangu decoction on rheumatoid arthritis (RA)Methods:Seventy Wistar rats were randomly divided into blank control group, model group, Jinwujiangu decoction high, middle and low different doses treatment group, Triterygium Wilfordii control group and Prednisone control group,10rats in each group. Except blank control group, the rest of the groups to establish the rat model of CIA, in the14stday of this process, the rats by gavage according to group for4weeks, each group free feeding and drinking.Observe joint swelling rate and AI before treatment, after the First weeks, second weeks, third weeks and the fourth weeks treatment. The rats were killed after4weeks, observe the joint pathological changes under light microscope by HE staining. Isolated synovial from rats joints, then detecting the expression of c-fos, c-jun, NF-κB/P65, NF-κB/P50and IκBα in synovial with Western blotting.Obtained image by using scanner, and determinated its’gray value by ImageJ2x, then Statistics and analysis of the results.Results:1、. The copy of the CIA rat model is successful. Compared with blank control group, the AI and joint swelling rate was significant differences in model group at the same time before treatment (P<0.01). After4weeks of treatment, there was a significant difference between the treatment groups and the model group (P<0.01).The downregulation of joint swelling rate and AI in low dose Jinwujiangu decoction group is less than other treatment groups, but there was significant difference at the same time point compared with model group (P<0.01).it was significant difference at the same time point compared with Prednisone control group (P<0.01). Compared with Triterygium Wilfordii control group, it was no significant difference at the same time point. Jinwujiangu decoction can downregulate the joint swelling rate and AI that dose-related.2、 HE staining:There was no inflammatory cell infiltration and the formation of vascular wing in rat synovium, there was no hyperplasia of cartilage and the cartilage cells arranged in neat rows in blank control group.The CIA model control group showed massive lymphocytic infiltration, edema, formation of vascular wing, cartilage tissue hyperplasia, the cartilage cells were clustered and by a large number of inflammatory cells infiltration, part of the cartilage calcification, necrosis, erosion to the bone and even destruction of the joint bone.The low dose Jinwujiangu decoction group showed inflammatory cell infiltration, hyperpalasia and edema of synovial tissue, cartilage cells were arranged in disorder, part of the cartilage calcification, erosion to the bone and destruction of the joint bone.The middle, high of Jinwujiangu decoction treatment group, Triterygium Wilfordii control group and Prednisone control group showed a small amount of neovascularization, synovial hyperplasia slightly, inflammatory cell infiltration have lessen, synovial tissue close to normal, cartilage tissue hyperplasia slightly and cells were arranged in disorder, the injure of cortical bone occasionally.3、The expression of the subunit c-fos and c-jun of AP-1was significant difference between the model group and the blank control group (P<0.01) Compared with the blank control group, the expression of c-fos and c-jun protein decreased in administration groups, have significant difference(P<0.01or P<0.05). there was no significant difference between different dose Jinwujiangu decoction groups and Triterygium Wilfordii control group, Prednisone control group. The inhibition of low,middle and high dose Jinwujiangu decoction group is dose-dependent, there was no significant difference among different dose groups.4、 Compared with the blank control group, The expression of NF-κB/P65, NF-κB/P50protein was significant difference in the model group (P<0.01) Compared with the model group, The expression of NF-κB/P65, NF-κB/P50protein in treatment groups is decreased, have significant difference (P<0.01or P<0.05) there was no significant difference between different dose Jinwujiangu decoction groups and Triterygium Wilfordii control group, Prednisone control group. Compared with the blank control group, The expression of IκBα protein is decreased in the model group, have significant difference (P<0.01). Compared with the model group, The expression of IκBα protein in administration groups is up-regulated, have significant difference (P<0.01or P<0.05). Compared with the Prednisone control group, The low dose Jinwujiangu decoction group is significant difference (P<0.05), The middle, high of Jinwujiangu decoction treatment group have no significant difference, there was no significant difference between different dose Jinwujiangu decoction groups and Triterygium Wilfordii control group.The inhibition of NF-κB/P65, NF-κB/P50and up-regulation of IκBα among different dose Jinwujiangu decoction group is dose-dependent, there was no significant difference among different dose groups (P>0.05)Conclusion:1、 Jinwujiangu decoction can downregulate the joint swelling rate and AI that dose-related.2、The pathological observation indicated that the Jinwujiangu decoction can protect joint in CIA rats.3. Jinwujiangu decoction can decrease the expression of c-Jun, c-Fos, NF-κB/P65and NF-κB/P50protein in CIA rats synovium, up-regulate the expression of IκBα. The inhibition of c-Jun, c-Fos, NF-κB/P65, NF-κB/P50and up-regulation of IκBα among different dose Jinwujiangu decoction group is dose-dependent.showed Jinwujiangu decoction can inhibit the AP-1and NF-κB signal pathway.