甲磺酸伊马替尼对高氧暴露新生大鼠肺保护作用及其机制

摘要

Objective To observe the protective effect of imatinib mesylate on hyperoxia-exposed lung injury in new-born rats and to investigate its mechanism.Methods Twenty-four newborn Sprague-Dawley rats were randomly divided in-to three groups, 8 in each group:the air-exposed group ( group A) , hyperoxia-exposed group ( group B) and hyperoxia-ex-posed +imatinib mesylate group ( group C) .The rats in the group C were intraperitoneally injected with 50 mg/( kg・ d) imatinib mesylate for 7 days, while rats in the groups A and B were injected with the same amount of normal saline for 7 days.Then all the rats were exposed to air, and were sacrificed 10 days later.The levels of platelet-derived growth factor-B ( PDGF-B) in bronchoalveolar lavage fluid ( BALF) and in serum were detected by ELISA, the expression of PDGF-B mRNA in tissue homogenates were detected by RT-PCR, and the value of lung damage score was calculated after He stai-ning under light microscope.Results There were no significant differences in the levels of PDGF-B in serum among three groups (all P>0.05).The levels of PDGF-B in BALF of groups A, B and C were (66.15 ±3.99), (103.91 ±6.79) and (85.08 ±6.33) pg/mL, and there was significant differences among these three groups (all P<0.05).The expres-sion of PDGF-B mRNA in the lung tissue homogenates was 0.26 ±0.04, 0.44 ±0.09 and 0.32 ±0.03, and there was sig-nificant difference among these three groups (all P<0.05).The lung damage score in the groups A, B and C was (0.62 ±0.21), (2.32 ±0.38) and (1.61 ±0.46) scores, and there were significant differences among these three groups (all P<0.05).Conclusion Imatinib mesylate protects hyperoxia-induced lung injury through PDGF and platelet-derived growth factor receptor.%目的：观察甲磺酸伊马替尼对高氧暴露新生大鼠的肺保护作用，并探讨其机制。方法将24只新生大鼠随机分为正常对照组、高氧对照组和伊马替尼组各8只。正常对照组暴露于正常室内空气中，高氧对照组和伊马替尼组暴露于高浓度氧气中；伊马替尼组高氧暴露的同时腹腔内注射甲磺酸伊马替尼50 mg／（kg・ d），正常对照组、高氧对照组注射等量生理盐水，共7天。造模10天处死大鼠，采用ELISA法检测各组血清及支气管肺泡灌洗液（ BALF）中血小板源性生长因子B亚型（ PDGF－B），RT－PCR法检测肺组织PDGF－B mRNA；肺组织石蜡包埋切片经HE染色，根据组织形态学改变进行肺损伤评分。结果三组血清PDGF－B比较，P＞0．05。正常对照组、高氧对照组和伊马替尼组BALF中PDGF－B水平分别为（66．15±3．99）、（103．91±6．79）、（85．08±6．33） pg／mL，PDGF－B mRNA相对表达分别为0．26±0．04、0．44±0．09、0．32±0．03，肺损伤评分分别为（0．62±0．21）、（2．32±0．38）、（1．61±0．46）分；上述指标组间两两比较，P均＜0．05。结论甲磺酸伊马替尼可能通过PDGF及其受体轴对高氧诱导的新生大鼠肺损伤产生保护作用。