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

【摘要】：目的：觀察辛伐他汀對博萊霉素(bleomycin, BLM)誘導纖維化大鼠肺組織10號染色體上缺失的磷酸酶與張力蛋白同源物基因(phosphase and tensin homology deleted on chromosome Ten, PTEN)、磷脂酰肌醇3-激酶(Phosphatidyl inositol 3-kinase, PI3K)、血管內(nèi)皮生長因子(Vascular endothelial growth factor, VEGF)表達的影響,探討辛伐他汀抗肺纖維化的作用機制。方法：健康SD大鼠45只(雄性,6周齡),被隨機分成3組,每組15只,A組：正常對照組、B組：博來霉素組、C組：辛伐他汀治療組；A組經(jīng)氣管內(nèi)一次性注入等體積生理鹽水,B、C組則以同樣的方法一次性注入博來霉素溶液(5mg/kg)制備肺纖維化模型,C組在BLM造模后第1天開始以辛伐他汀混懸液(10 mg/kg·d)灌胃,A、B組分別以等體積的生理鹽水(10ml/kg)每天灌胃處理。在造模后第7、14、28天取肺組織(每次每組隨機處死5只大鼠),堿性水解法檢測肺組織中羥脯氨酸(Hydroxyproline, Hyp)的含量,HE染色觀察肺泡炎、纖維化情況,免疫組化法檢測各組肺組織PTEN、PI3K、VEGF蛋白的表達,而用RT-PCR法檢測各組大鼠肺組織PTEN、PI3K、VEGFmRNA的表達。結果：①羥脯氨酸含量測定結果提示：與A組比較,B、C組大鼠肺組織Hyp的含量明顯增加,其中升高最顯著的是28天時的含量,差異有統(tǒng)計學意義；與B組比較,C組Hyp含量均有所降低,差異有統(tǒng)計學意義。②病理學的結果提示：A組大鼠肺組織結構清晰；B組第7d表現(xiàn)為輕度肺泡炎,少量成纖維細胞增生,第14d炎細胞浸潤較前加重,成纖維細胞增殖顯著,第28d肺纖維化明顯,成纖維細胞大量增生,膠原沉積明顯,肺泡腔塌陷或消失；而與B組相比較,C組肺泡炎和纖維化程度各相應時間點均有不同程度的減輕。③免疫組化和RT-PCR結果提示：各組之間相同時間點比較,B組肺組織PTEN明顯低于A、C組,差異有統(tǒng)計學意義；而C組肺組織PTEN明顯高于A組,差異有統(tǒng)計學意義；B組肺組織PI3K、VEGF表達明顯高于A、C組,差異有統(tǒng)計學意義；而C組PI3K、VEGF的表達低于B組,而較A組高,差異有統(tǒng)計學意義。結論：辛伐他汀抗肺纖維化的機制可能與其增強肺組織PTEN的表達,抑制PI3K及VEGF的表達有關。
[Abstract]:Aim: to observe the effect of simvastatin on phosphase and tensin homology deleted on chromosome Tenon, phosphatidyl inositol 3-kinase, PI3K homologue of bleomycin (BLM) -induced pulmonary fibrosis in rats with pulmonary fibrosis.The expression of vascular endothelial growth factor (VEGF) in vitro.To investigate the mechanism of simvastatin on pulmonary fibrosis.Methods: 45 healthy SD rats were randomly divided into 3 groups.Group A: normal control group: group B: bleomycin group: group C: simvastatin treatment group: simvastatin treatment group: simvastatin treatment group, group A, once injected into the trachea of the same volume of normal saline, the BHG group is in the same way, once injected with bleomycin solution (5 mg / kg).Lung fibrosis model group C was treated with simvastatin suspension for 10 mg/kg / d (n = 10) and normal saline (n = 10 ml / kg) daily in group C (n = 1) after BLM was established.Lung tissue (5 rats in each group were killed at random on the 7th day 1428 after modeling). The content of hydroxyproline (Hypypline) in lung tissue was detected by alkaline hydrolysis method and the alveolitis and fibrosis were observed by HE staining.Immunohistochemical method was used to detect the expression of VEGF protein in lung tissue of each group, while RT-PCR method was used to detect the expression of VEGF mRNA in lung tissue of rats.Results compared with group A, the content of Hyp in lung tissue of group C was significantly higher than that of group A, and the most significant increase was at day 28 (P < 0.05).Compared with group B, the content of Hyp in group C was lower than that in group B, and the difference was statistically significant. 2. The pathological results showed that the lung tissue structure of group B was clear and that of group B showed mild alveolitis and a small number of fibroblasts on the 7th day.On the 14th day, the infiltration of inflammatory cells was more serious, the proliferation of fibroblasts was obvious, the pulmonary fibrosis was obvious on the 28th day, the proliferation of fibroblasts and collagen deposition were obvious, and the alveolar cavity collapsed or disappeared.The results of immunohistochemistry and RT-PCR showed that the PTEN of lung tissue in group B was significantly lower than that in group A at the same time point, compared with group B, and the corresponding time points of alveolitis and fibrosis in group C were significantly lower than those in group A and C, and the results of immunohistochemistry and RT-PCR showed that the PTEN of lung tissue in group B was significantly lower than that in group A and C.The expression of PTEN in lung tissue of group C was significantly higher than that of group A, and the expression of PTEN in group B was significantly higher than that in group A (P < 0.05), while the expression of PTEN in group C was lower than that in group B and higher than that in group A.The difference is statistically significant.Conclusion: the mechanism of simvastatin on pulmonary fibrosis may be related to the increase of PTEN expression and the inhibition of PI3K and VEGF expression in lung tissue.
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965

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