CAJ | 학술논문

目的研究二甲双胍对Ⅱ型胶原诱导类风湿性关节炎大鼠模型的抗炎及关节保护的作用.方法 4℃下,将Ⅱ型胶原溶于醋酸中,制成混合液;再与完全弗氏佐剂以1∶1相配比制成乳剂.于大鼠尾部、肛周皮肤多点皮内注射0.3 mL乳剂;实验第7天重复操作,加强诱导1次.造模成功后,于实验第7天将大鼠随机分为5组,为高剂量二甲双胍组、低剂量二甲双胍组、甲氨蝶呤组、诱导组、正常对照组,每组10只,分别给予高剂量二甲双胍(100 mg·kg-1·d-1),低剂量二甲双胍(50 mg· kg-1·d-1),甲氨蝶呤(2.7 mg·kg-1·w-1)灌胃干预治疗,诱导组和正常对照组不给予药物,每隔2d对各组大鼠进行关节炎评分及距骨宽度测量;于第28天处死取材,再进行大鼠踝关节X线片,大鼠血清中炎症因子水平及抗炎因子水平等检测.结果连续观察大鼠后足关节炎评分及距骨宽度测量示:高剂量二甲双胍组关节炎评分及距骨宽度较诱导组显著降低(P＜0.05),其余两用药组较诱导组也有一定降低关节炎评分及距骨宽度的作用(P＜0.05);X线片示:高剂量二甲双胍组可显著保留关节结构并使其免受侵蚀,而剂量低二甲双胍组和甲氨蝶呤组效果比高剂量二甲双胍组较弱,关节结构破坏程度较轻;ELISA结果示:高剂量二甲双胍组可显著降低大鼠血清中炎症因子TNF-α、IL-1β、IL-6水平(P＜0.05),升高抗炎因子IL-10水平(P＜0.05);低剂量二甲双胍组及甲氨蝶呤组大鼠血清中炎症因子TNF-α、IL-1β、IL-6水平较诱导组有所降低(P＜0.05),抗炎因子IL-10水平也有升高(P＜0.05).结论二甲双胍对于Ⅱ型胶原诱导类风湿性关节炎大鼠模型有显著的抗炎及关节保护的作用.
목적 연구이갑쌍고대Ⅱ형효원유도류풍습성관절염대서모형적항염급관절보호적작용.방법 4℃하,장Ⅱ형효원용우작산중,제성혼합액;재여완전불씨좌제이1∶1상배비제성유제.우대서미부、항주피부다점피내주사0.3 mL유제;실험제7천중복조작,가강유도1차.조모성공후,우실험제7천장대서수궤분위5조,위고제량이갑쌍고조、저제량이갑쌍고조、갑안접령조、유도조、정상대조조,매조10지,분별급여고제량이갑쌍고(100 mg·kg-1·d-1),저제량이갑쌍고(50 mg· kg-1·d-1),갑안접령(2.7 mg·kg-1·w-1)관위간예치료,유도조화정상대조조불급여약물,매격2d대각조대서진행관절염평분급거골관도측량;우제28천처사취재,재진행대서과관절X선편,대서혈청중염증인자수평급항염인자수평등검측.결과 련속관찰대서후족관절염평분급거골관도측량시:고제량이갑쌍고조관절염평분급거골관도교유도조현저강저(P＜0.05),기여량용약조교유도조야유일정강저관절염평분급거골관도적작용(P＜0.05);X선편시:고제량이갑쌍고조가현저보류관절결구병사기면수침식,이제량저이갑쌍고조화갑안접령조효과비고제량이갑쌍고조교약,관절결구파배정도교경;ELISA결과시:고제량이갑쌍고조가현저강저대서혈청중염증인자TNF-α、IL-1β、IL-6수평(P＜0.05),승고항염인자IL-10수평(P＜0.05);저제량이갑쌍고조급갑안접령조대서혈청중염증인자TNF-α、IL-1β、IL-6수평교유도조유소강저(P＜0.05),항염인자IL-10수평야유승고(P＜0.05).결론이갑쌍고대우Ⅱ형효원유도류풍습성관절염대서모형유현저적항염급관절보호적작용.
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.