本文選題：糖尿病 + 1型��； 參考：《天津醫(yī)科大學》2015年碩士論文

【摘要】：研究背景:成纖維細胞生長因子21(FGF21)是成纖維細胞生長因子(FGF)家族的一員,最先由Nishimura等首次于2000年發(fā)現(xiàn),主要在肝臟及脂肪組織合成的內(nèi)分泌激素,可以以自分泌、旁分泌及內(nèi)分泌的方式發(fā)揮激素樣作用,并在糖脂代謝中起重要作用。一項新的研究發(fā)現(xiàn)FGF21的產(chǎn)生與氧化應(yīng)激有關(guān),而N-乙酰半胱氨酸(NAC)可以通過其自身-SH的還原性及脫乙酰基后生成GSH的特性,使組織對抗氧化應(yīng)激的能力增強。NAC能否通過其抗氧化作用調(diào)節(jié)糖尿病大鼠肝臟的FGF21的表達尚未見相關(guān)報道。研究目的:探討NAC對于DM大鼠肝臟FGF21表達的影響。研究方法:1.以Wistar大鼠為實驗動物,予以一次性注射STZ(45mg/kg)建立DM大鼠模型。隨機分為NC組、DM組及DM+NAC干預組,觀察周期分別為6W和12W。2.定期檢測大鼠一般情況及隨機血糖、血脂、肝酶學指標及MDA、SOD等指標變化。3.通過免疫組織化學法觀察肝臟中FGF21的表達位置及各組FGF21的相對表達量。4.采用Western Blot法檢測6W及12W各組FGF21蛋白在肝臟中的表達變化。5.應(yīng)用實時定量PCR技術(shù)檢測6周及12周各組肝臟FGF21mRNA的相對表達量。結(jié)果:1.成功建立1型糖尿病大鼠模型。2.與同期NC組大鼠比較,DM組及NAC干預組的大鼠其多飲、多尿、多食及消瘦癥狀明顯,體重下降顯著(P0.05),隨機血糖升高顯著(P0.05)。3.與同期NC組比較,DM組及NAC干預組其肝功血脂均明顯升高(P0.01);NAC組較同期DM組相比ALT、TG均有所改善,統(tǒng)計學差異顯著(P0.05),AST、TC有下降趨勢,但差異不顯著。4.與同期NC組比較,DM組及NAC組其MDA水平均明顯升高,SOD活性均明顯降低(P0.01);NAC同期DM組相比MDA水平有所下降,SOD活性有所上升,差異具有統(tǒng)計學意義(P0.05)。5.免疫組化結(jié)果顯示FGF21表達于肝細胞胞漿,以中央靜脈周圍較豐富,與NC組相比DM組表現(xiàn)為棕黃色顆粒的先增加后減少,NAC干預組則表現(xiàn)為棕黃色顆粒的逐漸增加。6.Western-Blot結(jié)果顯示W(wǎng)estern blot結(jié)果顯示DM 6周組及NAC 6周組FGF21表達量顯著高于同期NC組,差異具有統(tǒng)計學意義(P0.05)。DM 12周組FGF21表達量明顯低于同期NC組,差異具有統(tǒng)計學意義(P0.05),NAC干預12周組的FGF21表達量則明顯高于同期對照組。且隨著時間的延長糖尿病組FGF21蛋白表達量呈先升后降趨勢,而NAC干預組則呈逐漸上升趨勢。7.實時定量PCR結(jié)果顯示:DM 6W組FGF21mRNA相對表達顯著高于同期NC組及NAC干預6W組,統(tǒng)計學差異顯著(P0.05);DM 12 W組FGF21表達量明顯低于同期NC組及NAC干預組,統(tǒng)計學差異顯著(P0.05)。隨著觀察周期的延長,DM組及NAC干預組FGF21mRNA的表達均呈先升后降趨勢。結(jié)論:1.糖尿病可造成肝臟損傷,并造成氧化抗氧化系統(tǒng)的不平衡。2.6周及12周正常對照組大鼠其肝臟FGF21mRNA相對表達量及FGF21蛋白表達量均無明顯差異。3.與正常對照組相比,糖尿病組及NAC干預組肝臟FGF21的mRNA相對表達量均呈先升后降趨勢。4.隨糖尿病時間的延長,糖尿病組肝臟FGF21蛋白表達量呈先升后降趨勢;干預組肝臟FGF21蛋白表達呈逐漸上升趨勢。5.NAC可能通過抗氧化應(yīng)激作用保護肝臟,增加FGF21的表達,最終使脂代謝紊亂減輕。
[Abstract]:Background: fibroblast growth factor 21 (FGF21), a member of the fibroblast growth factor (FGF) family, was first discovered in 2000 by Nishimura, and was first discovered in 2000. The endocrine hormone, synthesized mainly in the liver and adipose tissue, can play a hormone like role in autocrine, paracrine and endogenous secretions, and play a heavy role in glycolipid metabolism. A new study found that the production of FGF21 is associated with oxidative stress, and N- acetyl cysteine (NAC) can produce GSH by its reducibility and deacetylation of its own -SH, so that the tissue against oxidative stress enhances the ability of.NAC to regulate the expression of FGF21 in the liver of diabetic rats by its antioxidant effect. Objective: To investigate the effect of NAC on the expression of FGF21 in the liver of DM rats. Methods: 1. a rat model of DM rats was established by injecting STZ (45mg/kg) with Wistar rats. The rats were randomly divided into NC group, DM group and DM+NAC intervention group. The observation period was 6W and 12W.2. regularly to detect general and random blood glucose in rats. Changes in blood lipids, liver enzymes, MDA, SOD and other indexes of.3., the expression of FGF21 in the liver and the relative expression of FGF21 in each group.4. were observed by immunohistochemistry. The expression of FGF21 protein in the liver was detected by Western Blot method and the expression of FGF21 protein in the liver was detected by Western Blot method. Results: 1. the results were as follows: 1. the rat model of type 1 diabetic rats was successfully established and compared with the NC group in the same period, the rats in the DM group and the NAC intervention group had more drink, polyuria, polydipsia and emaciation symptoms, the weight loss was significantly decreased (P0.05), the blood glucose increased significantly (P0.05).3. compared with that of the NC group, and the liver function in the DM group and the NAC intervention group increased significantly (P). 0.01): compared with the DM group in the same period, ALT and TG were all improved, and the statistical difference was significant (P0.05), AST, TC had a downward trend, but the difference was not significant between.4. and NC group in the same period, and the MDA level of DM group and NAC group increased obviously. The results of statistical significance (P0.05).5. immunohistochemical staining showed that FGF21 was expressed in the cytoplasm of the liver cell, which was rich around the central vein. Compared with the group NC, the DM group showed a first increase in brown yellow granules, and the NAC intervention group showed a gradual increase in the.6.Western-Blot result of brown yellow granules. The blot result of Western showed that DM 6 weeks group and NAC 6 were shown. The expression of FGF21 in the week group was significantly higher than that in the same period NC group. The difference was statistically significant (P0.05) in the.DM 12 week group, the expression of FGF21 was significantly lower than that in the same period NC group. The difference was statistically significant (P0.05). The FGF21 expression of NAC intervention in the 12 week group was significantly higher than that in the control group, and the expression of FGF21 protein in the diabetic group increased first and then decreased. Trend, while the NAC intervention group showed a gradual increase in.7. real-time quantitative PCR results. The relative expression of FGF21mRNA in DM 6W group was significantly higher than that of NC group and NAC intervention group 6W group, and the statistical difference was significant (P0.05), and DM 12 W group was significantly lower than that of the same period and the intervention group. The expression of FGF21mRNA in the group and the NAC intervention group all increased first and then descended. Conclusion: 1. diabetes can cause liver damage, and cause the imbalance.2.6 weeks and 12 weeks of the oxidative antioxidant system, the relative expression of FGF21mRNA and the expression of FGF21 protein in the liver of the normal control rats were not significantly different from that of the normal control group, the diabetic group and the NAC The mRNA relative expression of FGF21 in the liver of the intervention group increased first and then decreased with the prolongation of the time of diabetes. The expression of FGF21 protein in the liver of the diabetic group increased first and then descended, and the expression of FGF21 protein in the liver of the intervention group was gradually increasing and.5.NAC could protect the liver by antioxidant stress, and the expression of FGF21 was increased, and finally the lipid generation was made. Thanks to the derangement.

【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R587.1

【參考文獻】

相關(guān)碩士學位論文 前1條

1 楊西建;FGF21在對乙酰氨基酚誘導的小鼠急性肝功能衰竭中的作用研究[D];吉林大學;2014年

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本文編號：1785065