The Mechanism Of Fufang Zhujieshen Tablet In Treatment Of Adjuvant Arthritis Rat Based On JAK1/STAT3 Signaling Pathway

ObjectiveTo explore the action mechanism of JAK1/STAT3 pathway in the anti-inflammatory effect of Fufang Zhujieshen tablet.;And to observe the anti-inflammatory and anti-tumor effects of Fufang Zhujieshen tablet on adjuvant arthritis rats,MethodsClinical observation: Inpatients were randomly divided into methotrexate group and Fufang Zhujieshen tablet group according to inclusion criteria and diagnostic criteria.The methotrexate group was given methotrexate tablets 10mg/w + hydroxychloroquine tablets 0.25g/d,and Fufang Zhujieshen tablet group was supplemented with Fufang Zhujieshen tablets 1.6g/3times/d on the basis of methotrexate group for 8 weeks.Before and after treatment,the patient's general data were included,including the patient's gender,age,and course of disease;The clinical symptoms and signs such as morning stiffness time(h)and rheumatoid nodules(numbers);The patients were investigated by DAS28 score and HAQ score;The serum CRP,JAK1 and STAT3 content were detected by ELISA.;medication safety observations include WBC?PLT levels.SD rats were randomly divided into normal group,model group,methotrexate group and Fufang Zhujieshen tablet group(15 each)to establish a rat model of adjuvant arthritis.The rats in normal group and model group were given 1ml/kg/d saline,Fufang Zhujieshen tablet group was given Fufang Zhujieshen tablets(0.756 g g/kg/d),while the methotrexate group was given methotrexate(0.79mg/kg/qw).Whole treatment continued eight week.After treatment,the general conditions of rats in each group were observed including body weight,arthritis index and joint swelling.The pathological observation about the synovial tissue of the right knee joint in rats were performed.The levels of JAK1 and STAT3 in the serum of rats were detected by ELISA.The safety observation included detection of ALT,AST,SCr and BUN levels in rat serum;Western Blot method was used to detect the changes of JAK1 and STAT3 protein in the synovial tissue of right knee joint.ResultsClinical observation results: General data: There was no significant difference in gender,age and disease duration between methotrexate group and Fufang Zhujieshen tablet group(P>0.05).Comparison of clinical symptoms and signs Morning stiffness time(h)and rheumatoid nodules number between the two groups: Before treatment there was no significant difference between the two groups(P>0.05).Morning stiffness time(h)and rheumatoid nodules number after treatment in the methotrexate group was higher than that in Fufang Zhujieshen tablet group(P<0.05).Morning stiffness time(h)and rheumatoid nodules numbers after treatment in the methotrexate group was less than that before treatment(P<0.05).According to the differences in Fufang Zhujieshen tablet group,morning stiffness time(h)and rheumatoid nodules number was less than that before treatment(P<0.05).Concerning the time and group differences,the effect of Fufang Zhujieshen tablet group was better than that of methotrexate group.Comparison of DAS28 score and HAQ score between the two groups: There was no significant difference in HAQ and DAS28 scores before treatment(P>0.05).After treatment,the scores of HAQ and DAS28 were compared between the two groups,and the scores of the Fufang Zhujieshen tablet group was lower than that of the methotrexate group(P<0.05).The DAS28 and HAQ scores of methotrexate group before and after treatment were compared,and the score after treatment was lower than that before treatment(P<0.05).The DAS28 and HAQ scores of Fufang Zhujieshen tablet group before and after treatment were compared,the scores after treatment were lower than those before treatment(P<0.05).There was no significant difference between the two groups(P>0.05)before treatment with CRP,JAK1 and STAT3.After treatment,Fufang Zhujieshen was lower than the methotrexate group in CRP,JAK1 and STAT3 level,the methotrexate group was slightly higher than the normal value,and the bamboo ginseng group values were in the normal range(P<0.05).The levels of CRP,JAK1 and STAT3 in the methotrexate group were lower than those before treatment(P<0.05).The comparison of CRP,JAK1 and STAT3 before treatment in Fufang Zhujieshen tablet group was lower than that after treatment(P<0.05);there was no significant difference in WBC and PLT between the two groups before treatment(P>0.05).The levels of WBC and PLT after methotrexate treatment were lower than those before treatment and slightly lower than normal(P<0.05).There was no significant difference in WBC and PLT after treatment in two groups(P>0.05).General situation: Compared with the normal group,the model group lost weight,the swelling degree of the foot and the arthritis index were significantly increased;compared with the model group,the weight of each treatment group increased,the swelling degree of the foot and the arthritis index descended.Compared with the model group,the two treatment groups improved in these three aspects.ELISA showed that compared with the model group,the levels of JAK1 and STAT3 in the serum of the two treatment groups were significantly lower,and the methotrexate group was slightly better than the Fufang Zhujieshen tablet group(P<0.05).In terms of drug safety: ALT,AST,SCr,and BUN in the serum of the model group were on a sharp increase compared with the normal group;ALT,AST,SCr,BUN in the serum of the control group compared with the model group were increased(P<0.05),while the treatment group is not increased.Western Blot method: Distinguished the model group from the normal group,the content of JAK1 and STAT3 in the synovial tissue of the right knee joint in the model group had a dramatic increase.Compared with the model group,the contents of JAK1 and STAT3 in the synovial tissue in the right knee joint about the two treatment groups were greatly decreased.The effect of methotrexate was slightly better than that of Fufang Zhujieshen tablet group(P<0.05).ConclusionsFufang Zhujieshen tablet has anti-inflammatory effects on SD rat AA model;the effective mechanism of Fufang Zhujieshen tablet in the therapy of rheumatoid arthritis may reduce the expression of CRP?JAK1 and STAT3 proteins in serum and synovial tissue based on JAK1/STAT3 signal pathway;Fufang Zhujieshen tablet has no damaging effect on liver and kidney function.Compared with the adverse reactions of liver and kidney dysfunction and leukopenia caused by methotrexate tablets,the safety of the drug is slightly better than that of methotrexate tablets.