本文選題：小窩蛋白-1　切入點：高氧　出處：《山西醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:1.制備高氧誘導小鼠急性肺損傷(HALI)模型,觀察HALI肺組織中小窩蛋白-1(Cav-1)、磷酸化小窩蛋白-1(P-Cav-1-Y14)的表達情況,以及在HALI發(fā)生中的作用。2.觀察酪氨酸蛋白激酶抑制劑PP2對Cav-1、P-Cav-1-Y14表達的影響。3.探討抑制Cav-1磷酸化能否對肺組織炎癥因子TNF-α、IL-6的釋放產生影響。方法:健康雄性ICR小鼠24只,按照隨機數(shù)字表法分為四組。對照組:呼吸室內空氣;高氧暴露3d組(HO_23d組):置于自制氧氣艙內,吸入氧濃度95%;高氧暴露3d+酪氨酸蛋白激酶抑制劑PP2組(HO_23d+PP2組):置于自制氧氣艙內,吸入氧濃度95%,同時腹腔注射PP2 5mg×kg-1×d-1;酪氨酸蛋白激酶抑制劑PP2組(PP2組):呼吸室內空氣,同時腹腔注射PP2 5mg×kg-1×d-1。在光鏡下觀察各組小鼠肺臟病理學變化;采用Western blot檢測肺組織小窩蛋白-1(Cav-1)及磷酸化小窩蛋白-1(P-Cav-1-Y14)的表達;采用實時定量PCR(RT-PCR)法檢測肺組織TNF-α及IL-6 m RNA表達。結果:HO_23d組和HO_23d+PP2組小鼠肺組織Cav-1、P-Cav-1-Y14蛋白表達量以及肺組織TNF-α、IL-6 m RNA表達量均明顯高于對照組和PP2組(均P0.05),同時肺組織呈現(xiàn)炎癥損傷改變;HO_23d組上述指標均明顯高于HO_23d+PP2組(均P0.05),同時肺組織炎癥損傷程度也較HO_23d+PP2組顯著;對照組和PP2組上述指標比較差異無統(tǒng)計學意義(P0.05),肺組織未見明顯病理損傷改變。結論:高氧可通過上調肺組織Cav-1、P-Cav-1-Y14的表達,引起肺組織炎癥損傷;抑制Cav-1磷酸化可減少肺組織釋放TNF-α、IL-6等炎癥因子,對HALI有一定保護作用。
[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- 偽 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- 偽 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- 偽 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- 偽 -Cav-1-Y14 protein and the expression of TNF- 偽 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- 偽 and IL-6 in lung tissue, and has a protective effect on HALI.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R563.8

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