本文選題：肺纖維化 + 紅霉素��； 參考：《南華大學》2012年碩士論文

【摘要】：目的 使用博來霉素復制大鼠肺纖維化模型，探討整合素連接激酶（ILK）、E-鈣粘素（e-cadherin，E-cad）、α-平滑肌蛋白（α-SMA）在肺纖維化過程中的表達及紅霉素的干預作用。 方法 健康雄性SD大鼠90只，隨機分為6組，每組15只，分別為第1組正常對照組；第2組模型組；第3組造模前三天連續(xù)給紅霉素，然后予以博萊霉素（bleomycin，BLM）造模；第4組BLM造模后2h開始給紅霉素，共給14d；第5組BLM造模后第14d開始給紅霉素，至第28d；第6組BLM造模前三天連續(xù)給紅霉素至造模后第28d。2至6組氣管內予以BLM(5mg/g)制作肺纖維化動物模型，，1組氣管內予以等體積生理鹽水，造模后各組按方案進行給藥。分別于7、14、28d隨即各處死5只，取左肺組織放于4%甲醛固定后做HE染色及免疫組化檢測ILK、E-cad、α-SMA蛋白的表達；取右肺組織進行羥脯氨酸檢測和RT-PCR檢測ILKmRNA、E－cadherin mRNA、α-SMA mRNA的表達。 結果 1.HE染色顯示：第2組7d組織以炎癥反應為主，可見肺成纖維細胞；14d見大量炎性細胞浸潤，較多肺成纖維細胞；28d見大量肺成纖維細胞，說明肺纖維化模型形成。第2至6組病理改變趨勢相同，逐漸向肺纖維化發(fā)展，但第6組纖維化程度最輕。 2.HYP含量：7d、14d、28d與空白對照組比，2-6組含量均增高，且P＜0.05，以第2組升高最為明顯；3、5組各時間段HYP檢測與2組相比無明顯變化；4、6組予以紅霉素干預后，含量均有所下降，且P＜0.05以第6組28d最為顯著，P＜0.01。 3.RT-PCR、免疫組化顯示：在正常肺組織中，ILK、α-SMA表達為低表達，E-cad為高表達。肺纖維化發(fā)生時，與正常組織相比較，ILK、α-SMA表達增強（P＜0.05），E-cad表達減弱（P＜0.05）；予以紅霉素干預后，與模型組相比較，第4、6組ILK、α-SMA表達水平下降，E-cad上升（P＜0.05），以第6組28d最為明顯（P＜0.01）. 結論1、紅霉素可以預防博來霉素所致大鼠肺纖維化，其效果與早期用藥及療程有關。2、紅霉素防治肺纖維化作用機制可能與抑制ILK、α-SMA表達，增高E-cad水 平，延緩上皮細胞-間質轉化發(fā)展過程有關。
[Abstract]:Purpose To investigate the expression of E-cadherine-cadherin (E-cadherin) and 偽 -smooth muscle protein (偽 -SMA) in pulmonary fibrosis induced by bleomycin in rats, and to investigate the effect of erythromycin on it. Method 90 healthy male Sprague-Dawley rats were randomly divided into 6 groups, each group (n = 15): normal control group (group 1), model group (group 2), erythromycin (Erythromycin) (group 3) and bleomycin (BLM) (group 3). In group 4, erythromycin was given 2 hours after BLM was made, and erythromycin was given to BLM in group 5 on the 14th day. On the 28th day, the rats in the sixth group were given erythromycin three days before the model was made, and the rats in the 28d.2 to group 6 were given BLMN 5mg / g intratracheal administration. The rats in group 1 were given the same volume of normal saline in trachea. After the model was made, each group was given drugs according to the plan. The left lung tissues were fixed with 4% formaldehyde for HE staining and immunohistochemistry to detect the expression of ILK E-cadE and 偽 -SMA protein, and the right lung tissues were detected for hydroxyproline and RT-PCR for the expression of IL-K mRNA-E-cadherin mRNAin and 偽 -SMA mRNA. Result 1.HE staining showed that in group 2, inflammatory reaction was dominant at day 7. A large number of inflammatory cells were observed in lung fibroblasts on day 14, and a large number of fibroblasts were found in more fibroblasts on day 28, indicating the formation of pulmonary fibrosis model. The pathological changes in groups 2 to 6 showed the same trend and gradually developed to pulmonary fibrosis, but the degree of fibrosis in group 6 was the least. The content of 2.HYP in the control group was significantly higher than that in the control group for 14 days and 28 days, and the content of HYP in the second group was significantly higher than that in the control group (P < 0.05). The content of HYP in the second group was significantly higher than that in the control group (P < 0.05). And P < 0.05 was the most significant in the 6th group on the 28th day (P < 0.01). 3. RT-PCR.Immunohistochemistry showed that the expression of 偽 -SMA was low and the expression of 偽 -SMA was high in normal lung tissues. Compared with the normal tissue, the expression of ILK, 偽 -SMA and E-cad were decreased (P < 0.05) and the expression of 偽 -SMA was decreased (P < 0.01) in group 4 (P < 0.05), compared with that in model group (P < 0.05) after the intervention of erythromycin, the expression level of 偽 -SMA was decreased (P < 0.05) in group 4 (P < 0.05), especially in group 6 (P < 0.01) on the 28th day after treatment with Erythromycin, the expression of 偽 -SMA decreased significantly (P < 0.05), and the expression of 偽 -SMA increased significantly (P < 0.05). Conclusion 1.Erythromycin can prevent pulmonary fibrosis induced by bleomycin in rats, and its effect is related to early medication and course of treatment. The mechanism of erythromycin on pulmonary fibrosis may be to inhibit the expression of ILK, 偽 -SMA and increase E-cad water. It is related to delaying the process of epithelial-mesenchymal transformation.
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R563.9;R965

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