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A2M治療Ⅱ型膠原誘導(dǎo)性踝關(guān)節(jié)炎的療效評(píng)價(jià)

發(fā)布時(shí)間:2018-04-28 14:55

  本文選題:踝關(guān)節(jié) + 類風(fēng)濕性關(guān)節(jié)炎。 參考:《山西醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:1、CIA小鼠的踝關(guān)節(jié)腔中補(bǔ)充額外A2M,能否起到抑制炎癥、保護(hù)關(guān)節(jié)軟骨及骨的作用;2、較高濃度的A2M是否有更好的抑制炎癥及保護(hù)關(guān)節(jié)作用;3、FMT能否作為一種敏感的動(dòng)態(tài)活體生物成像監(jiān)測(cè)軟骨及骨損傷的手段。方法:選用健康2月齡雌性DBA/1小鼠60只,隨機(jī)平均分為4組,第1、2、3組進(jìn)行CIA造模,第4組作為陰性對(duì)照。于第33d時(shí)所有CIA小鼠踝關(guān)節(jié)均出現(xiàn)發(fā)紅及腫脹,于第35d時(shí)X光檢測(cè)踝關(guān)節(jié),鑒別其炎癥及關(guān)節(jié)破壞情況。于第36d、42d、49d時(shí),前3組右側(cè)踝關(guān)節(jié)腔內(nèi)分別注射濃度為0.04mg/ml、0.08mg/ml和0.12mg/ml的A2M溶液10ul。于第33d-57d,每4天1次,進(jìn)行小鼠尾靜脈注射ProSense FAST和MMPSense FAST熒光標(biāo)記物,并于每次注射標(biāo)記物后24h使用FMT對(duì)模型鼠進(jìn)行活體炎癥檢測(cè)。于第57d,FMT及X光檢測(cè)后處死小鼠,取踝關(guān)節(jié)進(jìn)行PCR、番紅O染色以及免疫組織化學(xué)檢測(cè)。結(jié)果:于第33d時(shí),所有CIA小鼠踝關(guān)節(jié)均出現(xiàn)發(fā)紅與腫脹,模型建立成功,第35d X光顯示,踝關(guān)節(jié)局部存在炎癥反應(yīng)但并無(wú)骨質(zhì)破壞。治療期間FMT結(jié)果顯示,A2M治療組炎癥反應(yīng)明顯低于陽(yáng)性對(duì)照組,有顯著統(tǒng)計(jì)學(xué)意義;且A2M濃度越高,炎癥抑制越明顯;另X線、PCR、番紅O染色及免疫組織化學(xué)結(jié)果均與FMT結(jié)果相一致,表明關(guān)節(jié)炎癥反應(yīng)減輕,同時(shí)治療組的A2M在一定程度上可以抑制滑膜增生、保護(hù)關(guān)節(jié)軟骨減輕骨質(zhì)破壞。結(jié)論:早期使用A2M治療可以有效抑制CIA動(dòng)物模型的炎癥反應(yīng),延緩病變進(jìn)展程度,且其濃度越高,效果越好;同時(shí)FMT可以成為一種有效的活體檢測(cè)方法,實(shí)時(shí)監(jiān)控并預(yù)測(cè)病情的發(fā)展程度。
[Abstract]:Objective to investigate whether the supplementation of extra A2M into the ankle cavity of the CIA mice can inhibit inflammation. The protective effect of articular cartilage and bone is 2%. Whether the higher concentration of A2M can inhibit inflammation and protect joints can FMT be used as a sensitive dynamic in vivo imaging to monitor cartilage and bone injury. Methods: 60 healthy 2 month old female DBA/1 mice were randomly divided into 4 groups. Group 1 and group 2 were used to model CIA, and group 4 was used as negative control. At the 33rd day, all the CIA mice showed redness and swelling of the ankle joint. At the 35th day, the ankle joint was detected by X-ray to distinguish the inflammation and joint destruction. On the 48th day of 36d, the first three groups were injected with 0.04 mg / ml 0.08 mg / ml A2M solution and 10 ululums respectively. ProSense FAST and MMPSense FAST fluorescent markers were injected into caudal vein of mice every 4 days at 33d-57d and FMT was used 24 hours after each injection to detect in vivo inflammation in model mice. The mice were killed after FMT and X ray examination on the 57th day, and the ankle joints were detected by PCR, Phanerin O staining and immunohistochemistry. Results: on the 33th day, all the CIA mice showed redness and swelling of the ankle joint, and the model was established successfully. On the 35th day, the local inflammation of the ankle joint was found, but no bone destruction was found. FMT results showed that the inflammatory response of A2M treatment group was significantly lower than that of the positive control group, and the higher the A2m concentration, the more obvious the inflammatory inhibition. The results of FMT showed that the reaction of arthritis was alleviated, and A2m in the treatment group could inhibit synovial hyperplasia and protect articular cartilage from bone destruction to some extent. Conclusion: early treatment with A2M can effectively inhibit the inflammatory response of CIA animal model and delay the progress of the disease, and the higher the concentration of A2m, the better the effect, and FMT can be an effective method for in vivo detection. Monitor and predict the development of the disease in real time.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R593.22

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