Effects of Mianan Fang on Serum Expression of IL-6,IL-1β,TNF-α and Hipp-ocampal Tissue BDNF Protein in Rats with Depression and Sleep Disorders
Objective Investigate the efficacy and mechanism of Chuanshi Tongbi decoction on the immune-in-flammatory injury of the synovial membrane in collagen 11-induced arthritis(CIA)model rats.Methods Specific patho-gen-free(SPF)male Sprague-Dawley(SD)rats,weighing 200±10 g,were used to establish the CIA model by injecting bovine CⅡ into the tail root.These model rats were divided into model group,positive drug group,and Chuanshi Tongbi treated decoction group according to the random number table,with 6 rats in each group.Another 6 unmodeled rats were taken as a normal group.The normal group and the model group were given deionized water by gavage at a dose of 10 ml/kg every other day.The positive drug group was given methotrexate at a dosage of 0.5 mg/kg per week by intraperitoneal injection.The Chuanshi Tongbi decoction group was administered crude drug at a dosage of 11.2 g/kg every other day by intragastric.The rats were sacrificed after continuous intervention for 4 weeks,and plasma,knee joint synovial membrane,and ankle joint specimens were collected.The pathological changes in the ankle joints of rats were observed by HE stai-ning.The protein expression levels of pJAK1,JAK1,p38,and GABRB1 in the knee joint synovium of rats were detected by Western blot.The expression levels of IL-6,STAT3,and SOCS1 in plasma were detected by ELISA.UHPLC-Q-Exac-tive Orbitrap MS was used to analyze the plasma metabolites.Results Compared with the normal group,rats in the model group showed significant synovium proliferation,severe bone destruction,and inflammatory cell infiltration in the ankle joints.Compared with the model group,rats in the Chuanshi Tongbi decoction group exhibited significant improvement in o-verall scores for joint bone destruction and joint lesions.Compared with the normal group,the expression levels of GABRB1 and SOCS1 protein in the model group were significantly decreased(P<0.01),while the expression levels of p38,pJAK1,IL-6,and STAT3 protein were significantly increased(P<0.01,P<0.05).Compared with the model group,the protein expression levels of GABRB1 and SOCS1 in the Chuanshi Tongbi decoction group and the positive drug group were signifi-cantly up-regulated(P<0.01,P<0.05),and the protein expression of p38,pJAK1,IL-6,and STAT3 were significant-ly inhibited(P<0.01).The up-regulation effect of GABRB1 and the inhibition effect of pJAK1 in the Chuanshi Tongbi decoction group were significantly better than those in the positive drug group(P<0.01).Plasma metabolites analysis re-vealed that glycerophospholipid metabolism,arachidonic acid metabolism,and sphingolipid metabolism pathways,along with related 50 metabolites,were closely related to the occurrence of this disease.Conclusion Chuanshi Tongbi decoction can effectively improve the immune-inflammatory and metabolic injury of joint synovium in CIA model rats.The mechanism may be related to the regulation of the GABRB1-SOCS1/JAK1/STAT3 signaling pathway and the regulation of lipid me-tabolism pathways.