本文選題：佐劑性關(guān)節(jié)炎 + 錳超氧化物歧化酶��； 參考：《安徽醫(yī)科大學(xué)》2016年碩士論文

【摘要】：背景：氧化應(yīng)激性反應(yīng)是導(dǎo)致類風(fēng)濕關(guān)節(jié)炎(rheumatoid arthritis, RA)的一個(gè)重要因素,長(zhǎng)期治療、生活方式的改變、關(guān)節(jié)疼痛和功能受限等使RA患者處于應(yīng)激狀態(tài),機(jī)體出現(xiàn)脂質(zhì)過(guò)氧化反應(yīng),氧自由基(oxygen free radical, ROS)的生成增加,而清除ROS的能力下降。佐劑性關(guān)節(jié)炎(adjuvant arthritis, AA)大鼠模型由于和RA在形態(tài)學(xué)上相似,且造模簡(jiǎn)單,是目前較為常用的RA動(dòng)物模型,常用于RA藥物篩選模型。真核細(xì)胞線粒體中含有錳超氧化物歧化酶(manganese superoxide dismutase, MnSOD),屬于金屬抗氧化酶,能夠特異性的將超氧陰離子自由基(superoxide anion free radical)(0.-)2轉(zhuǎn)化為H202和O2。MnSOD主要存在于線粒體,而線粒體是細(xì)胞內(nèi)氧化代謝和產(chǎn)生能量、自由基的重要場(chǎng)所,故其在抗氧化損傷中作用顯著。去乙�；�(sirtuins, SIRTs)家族中的SIRT3主要位于線粒體,是具有去乙�；富钚缘腟IRTs,具有調(diào)節(jié)線粒體的能量代謝和抗氧化應(yīng)激的作用。目的：通過(guò)建立弗氏佐劑性關(guān)節(jié)炎(AA)大鼠模型,觀察分析持續(xù)性的炎癥刺激有無(wú)引起肝臟生化及形態(tài)學(xué)上的改變,這種改變與氧化應(yīng)激性反應(yīng)是否具有相關(guān)性,并且探討肝臟錳超氧化物歧化酶(MnSOD)、去乙�；�3(Sirtuin3, SIRT3)的改變與AA大鼠肝臟損傷的關(guān)系。方法：弗氏完全佐劑(Freund's complete adjuvant, FCA)足趾皮下注射誘導(dǎo)SD大鼠從,造模后d 12、19、26,分批處死大鼠,計(jì)算肝指數(shù),檢測(cè)血清谷草轉(zhuǎn)氨酶(aspartate transaminase, AST)、谷丙轉(zhuǎn)氨酶(glutamic-pyruvic transaminase,ALT)、肝勻漿檢測(cè)丙二醛(methane dicarboxylic aldehyde, MDA)、谷胱甘肽過(guò)氧化物酶(glutathion peroxidase, GSH-Px)、超氧化物歧化酶(superoxide dismutase, SOD)的變化,肝組織免疫組化和Western blot檢測(cè)MnSOD、SIRT3蛋白表達(dá)變化。結(jié)果：與正常組大鼠比較,弗氏完全佐劑誘導(dǎo)的SD大鼠關(guān)節(jié)炎模型在造模后的3d即出現(xiàn)急性炎癥表現(xiàn),足爪、關(guān)節(jié)發(fā)紅腫脹,繼而踝關(guān)節(jié)背屈/趾屈活動(dòng)度減小,活動(dòng)受限,繼發(fā)性炎癥進(jìn)一步發(fā)展,說(shuō)明從大鼠模型建立成功。從大鼠造模d12后,肝臟指數(shù)升高,血清轉(zhuǎn)氨酶升高,肝勻漿中MDA升高,GSH-Px、SOD活性下降(P0.05或P0.01),肝組織中MnSOD、 SIRT3蛋白表達(dá)下降。從大鼠關(guān)節(jié)和肝臟HE染色可見(jiàn)：滑膜組織增生水腫,血管翳形成,滑膜組織內(nèi)小血管增生,擴(kuò)張充血,大量炎性細(xì)胞浸潤(rùn)。嚴(yán)重者出現(xiàn)軟骨的破壞和骨的侵蝕。炎癥后期關(guān)節(jié)間隙變窄,從而形成不可逆的關(guān)節(jié)改變；肝臟結(jié)構(gòu)損傷逐漸嚴(yán)重,表現(xiàn)為炎細(xì)胞浸潤(rùn),肝血竇充血,肝細(xì)胞有點(diǎn)片狀壞死。結(jié)論：AA模型組大鼠存在肝損傷,肝勻漿中氧化應(yīng)激指標(biāo)升高,其機(jī)制與肝臟中MnSOD和SIRT3表達(dá)有一定的關(guān)聯(lián)。
[Abstract]:Background: oxidative stress response is an important factor leading to rheumatoid arthritis (RA). Long-term treatment, changes in lifestyle, joint pain and limited function lead to stress and lipid peroxidation in RA patients. The formation of oxygen free radical, ROS) increased, while the ability of scavenging ROS decreased. Adjuvant arthritis (AA) rat model is a commonly used animal model for RA drug screening because it is similar to RA in morphology and simple in making model. The mitochondria of eukaryotic cells contain manganese superoxide dismutase, MnSODX, which belong to metal antioxidant enzymes, and can specifically transform superoxide anion free radical)(0.-)2 into H202 and O2.MnSOD mainly in mitochondria. Mitochondria are important sites for intracellular oxidative metabolism, energy production and free radical production, so mitochondria play a significant role in antioxidant damage. The SIRT3 of deacetylase sirtuins (SIRTs) family is mainly located in mitochondria and is a kind of SIRTs with deacetylase activity which can regulate mitochondrial energy metabolism and antioxidant stress. Aim: to establish a rat model of Freund's adjuvant arthritis (Freund's adjuvant arthritis) and to investigate whether the persistent inflammatory stimulation causes biochemical and morphological changes in the liver and whether the changes are related to the oxidative stress response. The relationship between liver manganese superoxide dismutase (MnSOD), deacetylase (3), Sirtuin 3 (SIRT3) and liver injury in AA rats was studied. Methods: Sprague-Dawley rats were induced by subcutaneous injection of Freundus complete adjuvant, FCA), a Freundus adjuvant. The rats were killed in batches and liver index was calculated. Serum glutamic-pyruvic transaminase (alt), aspartate transaminase (AST), glutamic-pyruvic transaminase (alt), malondialdehyde (MDA) methane dicarboxylic aldehyde, malondialdehyde (MDA), glutathione peroxidase (Glutathione peroxidase), glutathione peroxidase (GSH-PxD), superoxide dismutase (SOD), and the expression of MnSOD- SIRT3 protein in liver tissue were detected. Results: compared with the normal group, the SD rat model of arthritis induced by Freund's complete adjuvant showed acute inflammation, redness and swelling of the paw and joint on the 3rd day after the establishment of the model, and then the motion of the ankle joint was decreased and the movement was limited. Secondary inflammation was further developed, indicating success in the establishment of rat models. The liver index increased, serum aminotransferase increased, the activity of MDA increased in liver homogenate, the activity of GSH-PxX SOD decreased by P0.05 or P0.01A, and the expression of MnSOD and SIRT3 protein in liver tissue decreased. From the HE staining of the joints and livers of rats, the synovial tissue was proliferative and edema, pannus was formed, the small vessels in the synovial tissue proliferated, dilated and congested, and a large number of inflammatory cells infiltrated. Severe cases appear cartilage damage and bone erosion. In the late stage of inflammation, the joint space became narrower, which resulted in irreversible joint changes. The damage of liver structure was gradually serious, showing inflammatory cell infiltration, hepatic sinusoidal congestion, and hepatocyte necrosis. Conclusion there is liver injury and oxidative stress index in liver homogenate of rats in the weight AA group. The mechanism is related to the expression of MnSOD and SIRT3 in the liver.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R593.22

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 盧錦森;馬中飛;縱何香;葉桂萍;郭利梅;何舒寧;張夢(mèng)琳;陳曉宇;;白藜蘆醇對(duì)佐劑性關(guān)節(jié)炎大鼠血管內(nèi)皮因子表達(dá)的影響[J];安徽醫(yī)科大學(xué)學(xué)報(bào);2015年07期

2 瞿暢;丁晨;王君澤;高瞻;;基于Kinect體感交互技術(shù)的上肢關(guān)節(jié)活動(dòng)度測(cè)量方法[J];中國(guó)生物醫(yī)學(xué)工程學(xué)報(bào);2014年01期

3 張玲玲;陳尹;陳鏡宇;汪慶童;吳華勛;魏偉;;芍藥苷對(duì)膠原誘導(dǎo)性關(guān)節(jié)炎大鼠滑膜細(xì)胞Ras和Raf-1表達(dá)的影響[J];中國(guó)新藥雜志;2008年05期

4 陳柏松;徐玉東;鐘淑琦;馬彥文;馬月秋;;大鼠佐劑性關(guān)節(jié)炎模型的建立與評(píng)價(jià)[J];哈爾濱醫(yī)科大學(xué)學(xué)報(bào);2005年06期

，

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