辛伐他汀对纤维化大鼠肺组织PTEN、PI3K、VEGF表达的影响

发布时间：2018-04-18 11:37

本文选题：辛伐他汀 + 肺纤维化　；参考：《南华大学》2014年硕士论文

【摘要】：目的：观察辛伐他汀对博莱霉素(bleomycin, BLM)诱导纤维化大鼠肺组织10号染色体上缺失的磷酸酶与张力蛋白同源物基因(phosphase and tensin homology deleted on chromosome Ten, PTEN)、磷脂酰肌醇3-激酶(Phosphatidyl inositol 3-kinase, PI3K)、血管内皮生长因子(Vascular endothelial growth factor, VEGF)表达的影响,探讨辛伐他汀抗肺纤维化的作用机制。方法：健康SD大鼠45只(雄性,6周龄),被随机分成3组,每组15只,A组：正常对照组、B组：博来霉素组、C组：辛伐他汀治疗组；A组经气管内一次性注入等体积生理盐水,B、C组则以同样的方法一次性注入博来霉素溶液(5mg/kg)制备肺纤维化模型,C组在BLM造模后第1天开始以辛伐他汀混悬液(10 mg/kg·d)灌胃,A、B组分别以等体积的生理盐水(10ml/kg)每天灌胃处理。在造模后第7、14、28天取肺组织(每次每组随机处死5只大鼠),碱性水解法检测肺组织中羟脯氨酸(Hydroxyproline, Hyp)的含量,HE染色观察肺泡炎、纤维化情况,免疫组化法检测各组肺组织PTEN、PI3K、VEGF蛋白的表达,而用RT-PCR法检测各组大鼠肺组织PTEN、PI3K、VEGFmRNA的表达。结果：①羟脯氨酸含量测定结果提示：与A组比较,B、C组大鼠肺组织Hyp的含量明显增加,其中升高最显著的是28天时的含量,差异有统计学意义；与B组比较,C组Hyp含量均有所降低,差异有统计学意义。②病理学的结果提示：A组大鼠肺组织结构清晰；B组第7d表现为轻度肺泡炎,少量成纤维细胞增生,第14d炎细胞浸润较前加重,成纤维细胞增殖显著,第28d肺纤维化明显,成纤维细胞大量增生,胶原沉积明显,肺泡腔塌陷或消失；而与B组相比较,C组肺泡炎和纤维化程度各相应时间点均有不同程度的减轻。③免疫组化和RT-PCR结果提示：各组之间相同时间点比较,B组肺组织PTEN明显低于A、C组,差异有统计学意义；而C组肺组织PTEN明显高于A组,差异有统计学意义；B组肺组织PI3K、VEGF表达明显高于A、C组,差异有统计学意义；而C组PI3K、VEGF的表达低于B组,而较A组高,差异有统计学意义。结论：辛伐他汀抗肺纤维化的机制可能与其增强肺组织PTEN的表达,抑制PI3K及VEGF的表达有关。
[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.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

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