發(fā)布時間：2018-05-17 19:51

  本文選題：慢性間歇性缺氧 + 心房結(jié)構(gòu)重構(gòu)��； 參考：《天津醫(yī)科大學》2017年碩士論文

【摘要】：目的:通過建立慢性間歇性缺氧(CIH)大鼠實驗模型,觀察心房肌組織的一般病理變化和心房纖維化的情況,以及心房肌組織細胞外信號調(diào)節(jié)激酶1/2、磷酸化細胞外信號調(diào)節(jié)激酶1/2和核轉(zhuǎn)錄因子kappa B的表達情況,探討慢性間歇性缺氧對SD大鼠心房結(jié)構(gòu)重構(gòu)(ASR)的影響及其相關(guān)的纖維化信號傳導通路。方法:選取12只Sprague-Dawley(SD)健康雄性大鼠,每只體重在250-300g之間,普通飼料適應性喂養(yǎng)1周后,隨機分為對照組(CTL組)和慢性間歇性缺氧組(CIH組),其中CTL組4只大鼠,CIH組8只大鼠。CTL組普通飼料飼養(yǎng),每日自由進食、飲水、活動,CIH組給予每日間歇缺氧5小時處理,連續(xù)間歇缺氧3周,建立慢性間歇性缺氧大鼠實驗模型,CIH組每日除間歇缺氧5小時外,其余時間同CTL組一樣正常飼養(yǎng)。實驗期間觀察對比兩組大鼠的精神、進食、飲水等一般情況。3周實驗結(jié)束后,所有大鼠經(jīng)腹腔注射麻醉后打開胸腔,分離暴露心臟,分別剪取左、右心房肌組織,將組織固定于4%的甲醛溶液中,梯度酒精脫水后制作石蠟切片,并進行組織病理學染色。HE染色法觀察大鼠心房肌組織的一般病理變化;Masson染色法測量大鼠心房肌組織膠原容積分數(shù),評價大鼠心房肌組織膠原纖維增生情況;免疫組織化學染色法檢測大鼠心房肌組織細胞外信號調(diào)節(jié)激酶1/2(ERK1/2)、磷酸化細胞外信號調(diào)節(jié)激酶1/2(p-ERK1/2)和核轉(zhuǎn)錄因子kappa B(NF-κB)的蛋白表達水平并半定量分析,觀察ERK信號傳導通路和NF-κB信號傳導通路的變化。結(jié)果:1.HE染色結(jié)果顯示,與CTL組比較,CIH組大鼠心房肌組織細胞核大小不均,排列紊亂,心肌間隙增大。2.Masson染色結(jié)果顯示CIH組較CTL組大鼠心房肌組織間隙增大,心肌間質(zhì)纖維增生明顯,心房纖維化程度高。3.免疫組織化學染色結(jié)果顯示,CTL組和CIH組大鼠心房肌組織中ERK1/2、p-ERK1/2和NF-κB均有陽性表達,但與CTL組相比,CIH組大鼠心房肌組織ERK1/2蛋白表達水平升高,p-ERK1/2蛋白表達增加,p-ERK1/2/ERK1/2蛋白比值升高;NF-κB的表達增加。結(jié)論:1.慢性間歇性缺氧可引起大鼠心房肌組織細胞結(jié)構(gòu)紊亂,心房肌間質(zhì)纖維化,發(fā)生心房結(jié)構(gòu)重構(gòu)。2.慢性間歇性缺氧可激活ERK和NF-κB信號傳導通路,激活的ERK和NF-κB信號傳導通路參與了慢性間歇性缺氧過程中心房纖維化的形成,但其具體機制有待進一步研究。
[Abstract]:Objective: to observe the general pathological changes of atrial muscle tissue and atrial fibrosis by establishing a rat model of chronic intermittent hypoxia. And the expression of extracellular signal-regulated kinase 1 / 2, phosphorylated extracellular signal-regulated kinase 1 / 2 and nuclear transcription factor kappa B in atrial muscle, To investigate the effect of chronic intermittent hypoxia on atrial structural remodeling (ASR) and its related fibrosis signal transduction pathway in SD rats. Methods: twelve healthy male Sprague-Dawley (SD) rats, each weighing between 250 g and 300 g, were fed with normal diet for 1 week. The rats were randomly divided into two groups: control group (CTL group) and chronic intermittent hypoxia group (CBI group). Among them, 8 rats in CTL group were fed with normal diet, fed freely daily, drank water, and were treated with intermittent hypoxia for 5 hours per day. The experimental model of chronic intermittent hypoxia was established in rats with intermittent hypoxia for 3 weeks, except intermittent hypoxia for 5 hours per day, and the rest time was as normal as that in CTL group. During the experiment, the mental, eating and drinking conditions of the rats in the two groups were observed and compared. At the end of the experiment, all the rats were anesthetized by intraperitoneal injection to open the chest cavity, separate and expose the heart, and cut off the left and right atrial muscle tissues, respectively. The tissue was immobilized in 4% formaldehyde solution, and then the gradient alcohol was dehydrated to make paraffin sections. Histopathological staining and HE staining were used to observe the general pathological changes of rat atrial muscle tissue. Masson staining method was used to measure the collagen volume fraction of rat atrial muscle tissue and evaluate the proliferation of collagen fiber in rat atrial muscle tissue. The expressions of extracellular signal-regulated kinase 1 / 2 ERK1 / 2, phosphorylated extracellular signal-regulated kinase 1 / 2p-ERK1 / 2 and nuclear transcription factor kappa BNF- 魏 B were detected and semi-quantitatively analyzed by immunohistochemical staining. The changes of ERK signaling pathway and NF- 魏 B signaling pathway were observed. Results 1. The results of he staining showed that compared with the CTL group, the nuclei of the atrial myocytes in the CIH group were unevenly sized and disordered, and the myocardial gap was enlarged. 2. The results of Masson staining showed that the gap between the atrial myocytes of the CIH group and the CTL group was larger than that of the CTL group. Myocardial interstitial fiber proliferation is obvious, atrial fibrosis is high. 3. 3. The results of immunohistochemical staining showed that ERK1 / 2 p-ERK1 / 2 and NF- 魏 B were positive in rat atrial myocytes in CTL group and CIH group. However, compared with CTL group, the expression level of ERK1/2 protein in atrial muscle was increased and the ratio of p-ERK1 / 2 / ERK1 / 2 protein was increased, and the expression of NF- 魏 B was increased. Conclusion 1. Chronic intermittent hypoxia can lead to atrial tissue structure disorder, atrial interstitial fibrosis, atrial structural remodeling. 2. Chronic intermittent hypoxia can activate ERK and NF- 魏 B signal transduction pathway. Activated ERK and NF- 魏 B signal transduction pathway participate in the formation of atrial fibrosis during chronic intermittent hypoxia, but its specific mechanism needs further study.
【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】：2017
【分類號】：R541.75

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