小窝蛋白-1在高氧诱导小鼠急性肺损伤中的作用研究

发布时间：2018-03-15 08:54

本文选题：小窝蛋白-1　切入点：高氧　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:1.制备高氧诱导小鼠急性肺损伤(HALI)模型,观察HALI肺组织中小窝蛋白-1(Cav-1)、磷酸化小窝蛋白-1(P-Cav-1-Y14)的表达情况,以及在HALI发生中的作用。2.观察酪氨酸蛋白激酶抑制剂PP2对Cav-1、P-Cav-1-Y14表达的影响。3.探讨抑制Cav-1磷酸化能否对肺组织炎症因子TNF-α、IL-6的释放产生影响。方法:健康雄性ICR小鼠24只,按照随机数字表法分为四组。对照组:呼吸室内空气;高氧暴露3d组(HO_23d组):置于自制氧气舱内,吸入氧浓度95%;高氧暴露3d+酪氨酸蛋白激酶抑制剂PP2组(HO_23d+PP2组):置于自制氧气舱内,吸入氧浓度95%,同时腹腔注射PP2 5mg×kg-1×d-1;酪氨酸蛋白激酶抑制剂PP2组(PP2组):呼吸室内空气,同时腹腔注射PP2 5mg×kg-1×d-1。在光镜下观察各组小鼠肺脏病理学变化;采用Western blot检测肺组织小窝蛋白-1(Cav-1)及磷酸化小窝蛋白-1(P-Cav-1-Y14)的表达;采用实时定量PCR(RT-PCR)法检测肺组织TNF-α及IL-6 m RNA表达。结果:HO_23d组和HO_23d+PP2组小鼠肺组织Cav-1、P-Cav-1-Y14蛋白表达量以及肺组织TNF-α、IL-6 m RNA表达量均明显高于对照组和PP2组(均P0.05),同时肺组织呈现炎症损伤改变;HO_23d组上述指标均明显高于HO_23d+PP2组(均P0.05),同时肺组织炎症损伤程度也较HO_23d+PP2组显著;对照组和PP2组上述指标比较差异无统计学意义(P0.05),肺组织未见明显病理损伤改变。结论:高氧可通过上调肺组织Cav-1、P-Cav-1-Y14的表达,引起肺组织炎症损伤;抑制Cav-1磷酸化可减少肺组织释放TNF-α、IL-6等炎症因子,对HALI有一定保护作用。
[Abstract]:Objective to establish a mouse model of acute lung injury induced by hyperoxia, and to observe the expression of fossa protein -1 (Cav-1) and phosphorylated fossa protein P-Cav-1-Y14 (P-Cav-1-Y14) in HALI lung tissue. To observe the effect of tyrosine protein kinase inhibitor (PP2) on the expression of Cav-1 and P-Cav-1-Y14. To explore whether inhibiting the phosphorylation of Cav-1 can affect the release of TNF- 伪 IL-6 in lung tissue. Methods: 24 healthy male ICR mice, According to the method of random number table, the control group was divided into four groups: the control group: breathing room air; After 3 days of hyperoxia exposure, PP2 group, a tyrosine protein kinase inhibitor, was exposed to hyperoxia for 3 days. The PP2 group was placed in a self-made oxygen chamber, inhaled oxygen concentration 95% and injected intraperitoneally with PP2 5 mg 脳 kg-1 脳 d -1; PP2 group, a tyrosine protein kinase inhibitor group, was given intraperitoneal injection of PP2 5 mg 脳 kg-1 脳 d -1. At the same time, PP2 5mg 脳 kg-1 脳 d-1 was injected intraperitoneally. The pathological changes of lung were observed under light microscope, the expression of fossa protein -1 (Cav-1) and phosphorylated fossa protein (P-Cav-1-Y14) in lung tissue were detected by Western blot. The expression of TNF- 伪 and IL-6 m RNA in lung tissue was detected by real-time quantitative PCR- RT-PCR.Results the expression of Cav-1 P-Cav-1-Y14 protein and TNF- 伪 IL-6 m RNA in lung tissue were significantly higher than those in control group and PP2 group (both P0.055.Results the expression of TNF- 伪 -Cav-1-Y14 protein and the expression of TNF- 伪 IL-6 m RNA in lung tissue were significantly higher than those in control group and PP2 group (P0.05). The above indexes were significantly higher in HOD group than in HO_23d PP2 group (all P 0.05), and the degree of inflammatory injury in lung tissue was significantly higher than that in HO_23d PP2 group. There was no significant difference in the above indexes between the control group and the PP2 group. There were no obvious pathological changes in the lung tissue. Conclusion: hyperoxia can induce inflammatory injury of lung tissue by up-regulating the expression of Cav-1 P-Cav-1-Y14. Inhibiting the phosphorylation of Cav-1 can reduce the release of inflammatory factors such as TNF- 伪 and IL-6 in lung tissue, and has a protective effect on HALI.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.8

【参考文献】