Effect of metformin in vivo on the inhibition of inflammation and joint protection of the collagen-induced arthritis rat model

Abstract

Objective To verify the effect of metformin in vivo on the inhibition of inflammation and joint protection of the collagen-induced arthritis (CIA) rat model.Methods Under 4 ℃,dissolved type]Ⅱ collagen into acetic acid.In order to made the mixture into emulsion,blended it with complete freund's adjuvant to 1∶ 1.Gave several spots intraperitoneal injection of 0.3 mL emulsion in the rat tail and the skin around anus.Repeat the experi-mental operation on the 7th day to strengthen the induction.After the success of the induction,gave CIA rat models high doses of metformin(100 mg.kg-1 · d-1),low doses of metformin(50 mg · kg-1 · d-1) and methotrexate (2.7 mg · kg-1 · w-1) for treatment by gavage on the 7th day.Evaluated the arthritis score of each group of rats and measured the width of talus every two days.Executed rats and drew materials on the 28th day,then shot X-ray films of the ankle of rat and detected the levels of inflammatory and anti-inflammatory factors in rat serum by Elisa.Results After continuous observation rat foot arthritis scoring and measurement from talus width:arthritis scoring of high doses of metformin group was obviously lower than other induced groups (P ＜ 0.05),talus width is also much smaller(P ＜ 0.05) ; the rest of the treatment groups also has a certain effect on reducing arthritis score and the width of talus compared to the induced group (P ＜ 0.05).X-ray radiography show:high doses of metformin group can significantly save joint structure and make joint clearance clear; the treatment effect of the rest treatment groups are not better than high dose group,also has severe soft tissue swelling,bone absorption,joint disintegration and severe damage.Elisa show:High doses of metformin can lower the level of inflammatory factors-TNF-α,IL1 β,IL-6 (P ＜ 0.05),also can rise the level of anti-inflammatory factor-IL-10 obviously(P ＜ 0.05).Low doses of metformin and MTX have the similar effect (P ＜ 0.05),but not more significant than high doses of metformin.Conclusions Metformin in vivo can significantly Inhibit the inflammation and protect the joint structure of the collagen-induced arthritis (CIA) rat model. Key words: Metformin ; Type Ⅱ collagen; Arthritis, rheumatoid ; Inflammation; Joints, protection