目的:探讨外源性锌离子对大鼠肺组织中表皮生长因子受体(EGFR)的表达与活化的影响及可能机制。方法:20只大鼠随机分为4组:二甲基亚砜(DMSO)+PBS组、DMSO+硫酸锌组、PD153035+PBS组和PD153035+硫酸锌组,每组5只。麻醉大鼠后,根据分组情况,采用支气管灌注法分别用DMSO或1μmol/L的PD153035溶液进行预灌注,灌注剂量为0.5mL/kg,约30min后同法分别灌注PBS或100μmol/L的硫酸锌溶液,灌注剂量为1mL/kg。8h后将大鼠处死,制备肺匀浆,离心收集匀浆上清中的蛋白,用Westernblot检测EGFR的表达及磷酸化水平(即活化量)。结果:预灌注PD153035可降低大鼠肺组织EGFR的表达水平及活化量,灌注硫酸锌可致大鼠肺组织EGFR的表达水平及活化量升高,二者合用,有交互作用(EGFR的表达水平:F预灌注=249.896,F灌注=242.127,F交互=305.643;EGFR的活化量:F预灌注=252.347,F灌注=264.115,F交互=294.239,P均〈0.05)。结论:气管灌注外源性锌离子可致大鼠肺组织中EGFR的表达水平与活化量增加,其机制可能与酪氨酸激酶的磷酸化有关。
Aim:To observe the effects of exogenous zinc solution on expression and activation of EGF receptor(EGFR) in rat lung tissue and the possible mechanism.Methods:Twenty healthy Wistar rats were randomly allocated into 4 groups(DMSO+PBS,DMSO+zinc sulfate,PD153035+PBS,PD153035+zinc sulfate),and each group had 5 rats.After anesthesia,DMSO or PD153035(1 μmol/L) was pre-instilled accordingly at 0.5 mL/kg,and after 30 min,PBS or zinc sulfate(100 μmol/L) was instilled.The rats were sacrificed and lung tissue was homogenized.The supernatant protein was subjected to Western blot for detection of EGFR expression and phosphorylation.Results:Pre-instillation of PD153035 could down-regulate the expression and phosphorylation of EGFR,instillation of zinc sulfate could up-regulate the expression and phosphorylation of EGFR,and the 2 factors had interaction(EGFR:Fpre-instillation=249.896,Finstillation=242.127,Finteraction=305.643;EGFR phosphorylation:Fpre-instillation=252.347,Finstillation=264.115,Finteraction=294.239,all P0.05).Conclusion:Tracheal instillation of zinc sulfate increases EGFR expression and phosphorylation in rat lungs,which may be involved in the phosphorylation of tyrosine kinase.