本文選題：肺纖維化 + 辛伐他汀��； 參考：《南華大學(xué)》2014年碩士論文

【摘要】：【目的】 建立博來(lái)霉素(bleomycin, BLM)誘導(dǎo)的大鼠肺纖維化模型，探討Snail1、E-鈣粘素（E-cadherin, E-cad）、波形蛋白（Vimentin, VIM）在肺纖維化過(guò)程中的表達(dá)及辛伐他汀的干預(yù)作用。 【方法】 選用健康雄性SD大鼠60只，隨機(jī)分為4組，每組15只：A組為對(duì)照組；B組為模型組（BLM組）；C組為SIM5mg組，造模后第1天開(kāi)始連續(xù)每天給予辛伐他�。�5mg/kg）溶液灌胃；D組為SIM10mg組，造模后第1天開(kāi)始連續(xù)每天給予辛伐他汀（10mg/Kg）溶液灌胃。B-D組一次性氣管內(nèi)滴注BLM（5mg/Kg）制造肺纖維化動(dòng)物模型。A組氣管內(nèi)給予等體積的生理鹽水。分別于第7、14、28天隨機(jī)各處死5只，堿性水解法檢測(cè)肺組織羥脯氨酸（HYP）含量；HE染色觀察肺組織肺泡炎和纖維化變化；RT-PCR法檢測(cè)Snail1mRNA、E-cad mRNA、VIM mRNA的表達(dá)；免疫組織化學(xué)技術(shù)SP法檢測(cè)Snail1蛋白、E-cad蛋白、VIM蛋白的表達(dá)。 【結(jié)果】 1. HYP含量 與A組比較，7d、14d、28d時(shí)B、C及D組大鼠肺組織HYP含量均有升高，差異有統(tǒng)計(jì)學(xué)意義（P㩳0.05），以B組HYP含量最高。與B組比較，C組、D組HYP含量均有下降，D組低于C組，其差異有統(tǒng)計(jì)學(xué)意義，以D組28d下降明顯。 2.病理改變（HE染色） A組大鼠肺組織結(jié)構(gòu)正常，肺泡間隔未見(jiàn)增寬，無(wú)炎性細(xì)胞浸潤(rùn)，無(wú)纖維化改變。B組7d肺組織以炎癥反應(yīng)為主；14d肺組織結(jié)構(gòu)破壞，可見(jiàn)較多炎性細(xì)胞和成纖維細(xì)胞；28d肺組織結(jié)構(gòu)破壞嚴(yán)重，成纖維細(xì)胞增殖，肺纖維化形成。C、D組肺泡炎癥及纖維化程度較B組不同程度減輕。 3. Snail1、Vimentin及E-cad表達(dá)檢測(cè) 7d、14d、28d時(shí)，A組Snail1、Vimentin為低表達(dá)，E-cad為高表達(dá)；B組Snail1、Vimentin表達(dá)增高，E-cad表達(dá)減低，差異有統(tǒng)計(jì)學(xué)意義（P㩳0.05）；辛伐他汀干預(yù)后，與B組比較，C、D組Snail1、Vimentin表達(dá)不同程度減低，E-cad表達(dá)不同程度升高，其差異均有統(tǒng)計(jì)學(xué)意義（P0.05），以D組28天最為明顯（P0.05）。 【結(jié)論】 1.辛伐他汀能夠減輕BLM誘導(dǎo)的大鼠肺纖維化程度。 2.辛伐他汀抗纖維化機(jī)制可能與抑制Snail1、Vimentin表達(dá)，促進(jìn)E-cad表達(dá)，，延緩上皮細(xì)胞間質(zhì)轉(zhuǎn)化有關(guān)。
[Abstract]:[purpose] A rat model of pulmonary fibrosis induced by bleomycin (BLM) was established to investigate the expression of Snail1 E-cadherin E-cadherin and vimentin Vimentin in the process of pulmonary fibrosis and the intervention of simvastatin. [methods] Sixty male Sprague-Dawley rats were randomly divided into 4 groups. 15 rats in each group were divided into two groups: control group (n = 15), model group B (n = 15), SIM5mg group C (n = 15) and simvastatin group (n = 5 mg / kg). Group D was treated with simvastatin (5 mg / kg) daily as SIM10mg group. One day after the model was established, the rats in group A were given simvastatin 10 mg / kg) solution intravenously intratracheal instillation of BLM5 mg / kg) to make pulmonary fibrosis animal model. Group A was given normal saline in the trachea of the same volume. Five rats were killed randomly on day 7, 14 and 28, respectively. The content of hydroxyproline (HYP) in lung tissue was detected by alkaline hydrolysis method and the changes of pulmonary alveolitis and fibrosis were observed by HE staining. The expression of Snail1 mRNA-E-cad mRNAVIM mRNA was detected by RT-PCR. Immunohistochemistry SP method was used to detect the expression of E-cad protein and vim protein in Snail1. [results] 1. HYP content Compared with group A, the content of HYP in lung tissue of group C and group D increased at 14 days and 28 days, and the difference was statistically significant. The content of HYP in group B was the highest. Compared with group B, the content of HYP in group C was lower than that in group C, and the difference was statistically significant, especially in group D for 28 days. 2. Histopathological changes (HE staining) In group A, the lung tissue structure was normal, alveolar septum was not enlarged, no inflammatory cells were infiltrated, and no fibrosis was observed. It can be seen that more inflammatory cells and fibroblasts destroyed the lung tissue structure seriously at 28 days, the proliferation of fibroblasts and the degree of alveolar inflammation and fibrosis in group C. Con D were reduced compared with those in group B. 3. Detection of vimentin and E-cad expression in Snail1 The expression of Snail1Vimentin in group A was lower than that in group B, and the expression of Vimentin in group B was significantly higher than that in group B (P < 0.05), and the expression of Snail1Vimentin in group C was lower than that in group B, and the expression of E-cad was increased in group C (P < 0.05) after treatment with simvastatin, and the expression of Snail1Vimentin in group A was significantly lower than that in group B (P < 0.05), and the expression of Vimentin in group A was significantly lower than that in group B (P < 0.05). The difference was statistically significant (P 0.05), especially in group D (28 days). [conclusion] 1. Simvastatin can reduce the degree of pulmonary fibrosis induced by BLM in rats. 2. The anti-fibrosis mechanism of simvastatin may be related to the inhibition of Snail1Vimentin expression, the promotion of E-cad expression and the delay of epithelial interstitial transformation.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R563

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 黃珊;張文雍;潘春球;羅薇;余常輝;孟瑩;李旭;;膽管結(jié)扎誘導(dǎo)的肝纖維化大鼠肝臟上皮間質(zhì)表型的變化[J];南方醫(yī)科大學(xué)學(xué)報(bào);2012年02期

2 彭紅霞;陳明;張超;歐三桃;劉斌;;Akt信號(hào)蛋白在阿托伐他汀作用于UUO大鼠腎小管-間質(zhì)中的表達(dá)[J];中國(guó)病理生理雜志;2008年06期

本文編號(hào)：1807512