林白桦,贾勇士,毕爱红.吉非替尼在小鼠肺照射后不同时段给药对肺损伤影响[J].肿瘤学杂志,2017,23(1):13-19.
吉非替尼在小鼠肺照射后不同时段给药对肺损伤影响
Effect of Gefitinibon Radiation-Induced Lung Injury in C57 Mice after Different Time Administration
投稿时间:2016-09-18  
DOI:10.11735/j.issn.1671-170X.2017.01.B003
中文关键词:  吉非替尼  肺损伤  羟脯氨酸  转化生长因子-β1
英文关键词:gefitinib  lung injury  hydroxyproline  transforming growth factor-β1
基金项目:浙江省医药卫生一般研究计划(2013KYB027)
作者单位
林白桦 浙江省人民医院 
贾勇士 浙江省人民医院 
毕爱红 浙江省人民医院 
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中文摘要:
      摘 要:[目的] 观察不同时段给予吉非替尼对C57BL 小鼠放射性肺损伤的影响。[方法] 将128只C57BL雌性小鼠随机分组分为8组:(1)照射+早期予生理盐水组(A组)16只,全肺单次照射13Gy,在照射后立即第一次给生理盐水,以后每天均灌胃给药至第15d;(2)照射+晚期予生理盐水组(B组)16只,全肺单次照射13Gy,在照射后第15d第一次给生理盐水,以后每天均灌胃给药至第30d;(3)早期给予生理盐水组(C组)16只,在照射组照射后立即第一次给生理盐水,以后每天均灌胃给药至第15d;(4)晚期给予生理盐水组(D组)16只,在照射组照射后第15d第一次给生理盐水,以后每天均灌胃给药至第30d;(5)早期给药组(E组)16只,在照射组照射后立即第一次给药,以后每天均灌胃给药至第15d,给药剂量200mg/kg·d;(6)晚期给药组(F组)16只,在照射组照射后第15d第一次给药,以后每天均灌胃给药至第30d,给药剂量200mg/kg·d;(7)照射+早期给药组(G组)16只,全肺单次照射13Gy后立即第一次给药,以后每天均灌胃给药至第15d,给药剂量200mg/kg·d;(8)照射+晚期给药组(H组)16只,全肺单次照射13Gy后第15d第一次给药,以后每天均灌胃给药至第30d,给药剂量200mg/kg·d。在照射后30d、60d处死小鼠后取部分肺组织HE染色,检测血清转化生长因子β1(transforming growth factor-β1,TGF-β1)水平、以及部分肺组织羟脯氨酸(hydroxyproline,HYP)水平。[结果] 病理学检查显示,照射+晚期给药组(H组)在照射后60d时较其他照射组肺部损伤反应较轻。统计分析提示,各组之间TGF-β1和HYP水平比较有统计学差异(P均<0.01)。照射、给药、时间因素对小鼠血清中TGF-β1和HYP水平有统计学差异(P<0.05)。[结论]200mg/kg·d给药剂量情况下吉非替尼未显示明显的与照射累加的肺损伤,照射后晚期给予吉非替尼具有减轻放射性肺损伤作用。
英文摘要:
      Abstract:[Objective] To explore the effect of gefitinib on radiation-induced lung injury by administered it to C57 mice which had whole lung irradiation at different time periods postirradiation. [Methods] One hundred twenty-eight mice C57/BL(female) were divided into 8 groups by random digits table method. There were 16 mice in every groups. Irradiation + normal saline group at early phase(A),irradiation + normal saline group at late phase(B),irradiation + gefitinib group at early phase (G) and irradiation +gefitinib group at late phase(H) were irradiated first. Irradiation method:10MV-X ray,via the anterior chest,whole lung irradiation with 13Gy by single dose. Drug delivering method:Group A and G were given saline or gefitinib(200mg/kg·d) by gavage after irradiation on day 0 to day 15. Group B and H were given saline or gefitinib(200mg/kg·d) after irradiation on day 15 to day 30,once a day. Normal saline group at early phase(group C),normal saline group at late phase(group D),gefitinib group at early phase(group E) and gefitinib at late phase(group F) were given saline or gefitinib(200mg/kg·d) by gavage after other groups were irradiated at corresponding time periods. [Results] The inflammation in group H was lighter than that in the other groups which had been irradiated at 60 days. Gefitinib,irradiation and time factor had significant effect about TGF-β1 levels of serum(P<0.05). Time and irradiation factor had significant effect about HYP levels of lung tissue(P<0.01).[Conclusions] It doesn’t shown additive lung injury when given gefitinib(200mg/kg·d) after irradiation. Gefitinib could lighten radiation-induced lung injury when it is given at right time after irradiated.
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