摘要
目的观察吉西他滨不同给药方式对鼠放射性肺损伤的影响,并对其分子机制进行探讨。方法雄性BALB/C鼠,体重25g左右,随机分为空白对照(C)组、单纯照射(R)组、单纯给药(G)组、先给药后照射(PG+R)组、照射与同期给药(R+CG)组,每组80只。实验观察共8个月。采用6MVX线照射,照射面积2.0cm×2.5cm,照射剂量25Gy分5次。吉西他滨药量80mg/(kg·d),第1、5天腹腔给药。G组给药后第1个月始,每周镜下计数炎细胞总数及分类。每月取左肺组织进行羟脯氨酸含量与病理学检测,右肺用于TGF-β1、EGF和ICAM-1免疫组织化学分析。每月从处死小鼠心脏取血浆100μl用于TGF-β1、EGF和ICAM-1的检测。结果吉西他滨对肺损伤早期主要是炎性细胞渗出(中性粒细胞>90%),实验后1、3、6个月分别以渗出、增生和纤维化为主。R+CG组羟脯氨酸含量第5个月开始明显高于其他组(P<0.01),并持续到最后。R+CG组血浆ICAM-1含量照射后第1个月明显高于其他组(P<0.01),第2个月以后开始下降。R+CG组血浆EGF含量在照射后第2、3个月明显高于其他组(P<0.01),第4个月后开始下降;TGF-β1含量在照射后第3个月明显高于其他组(P<0.01),以后含量相对稳定。R+CG组ICAM-1表达在第1个月时明显高于其他组(P<0.01),第2个月后开始下调;EGF表达在第2、3个月时明显高于其他组(P<0.01),第4个月后开始下调;TGF-β1表达第3个月开始明显高于其他组(P<0.01),以后表达相似。结论经病理组织学及羟脯氨酸、TGF-β1、EGF、ICAM-1含量和免疫组织化学分析,照射与吉西他滨同期给药可明显增加放射性肺损伤的发生。
Objective To evaluate the degree of the increase of radiation-induced pulmonary injury by gemcitabine given at different intervals and to probe the molecular mechanism of radiation-induced pulmonary injury. Methods BALB/C male mice with body weight around 25 g were divided randomly into five groups： control group（C） ; gemcitabine group（G） ;irradiation group （R） ; gemcitabine followed by irradiation group（ PG ＋ R ） ; and irradiation plus concurrent gemcitabine group（R ＋ CG） ,with 80 mice each group. All were observed until the 8th month. The thorax of mice were irridiated by 6 MV X-ray with 25 Gy in 5 fractions through 2.0 cm × 2.5 cm port. Mice of G, PG ＋ R and R ＋ CG groups were injected with gemcitabine 80 mg/（ kg·d） into the peritoneal cavity on the fast and fifth days. In each week, inflammatory cells were classified and counted under light microscope in the first month in G group. The left lung was used to analyze the content of hydmxyproline and pathology each month; the fight lung was used to analyze the expression of intercellular adhesion molecule-1 （ICAM-1）, epidermal growth factor（EGF） and transforming growth factor-β1 （TGF-β1） by immunohistochemical method. Plasma ICAM- 1, EGF and TGF-β1 level were detected by ELISA each month. Results The exudation of inflammatory cells （neutrophilic leukocyte 〉 90% ） was a forepart change of gemcitabine-induced lung injury in the fast month in G group, but the exudation, proliferation and fibrosis dominated in the 1,3 and 6 months in R ＋ CG group. Hydroxyproline content of lung-irridiated tissue was increased from the 5th month and lasted to months 6,7 and 8, and its content in the R ＋ CG group was higher than that in the other groups（ P 〈 0.01）. Plasma ICAM-1 level in R ＋ CG group was higher than that in the other groups（ P 〈 0.01） in the the month, and decreased after two months. Plasma EGF level was mainly increased in months 2 and 3, and its level in the R ＋ CG group was higher than that in the other groups（ P 〈 0.01）.It decreased after the 4th month. Plasma TGF-β1 level was increased from the 3rd momth and lasted to the 8th month, and its level in R ＋ CG group was higher than that in the other groups（ P 〈 0.01 ）. Conclusion Irradiation combined with concurrent gemcibine can sigificantly increase radiation-induced lung injury through pathological analysis, hydroxyproline content of lung-irridiated tissue, TGF-β1, ICAM-1, EGF level of plasma changes and immunohistochemical expression.
出处
《中华放射肿瘤学杂志》
CSCD
北大核心
2006年第2期124-128,共5页
Chinese Journal of Radiation Oncology
基金
黑龙江省科技厅攻关资助项目(20010101029-00)
关键词
辐射损伤
实验性
肺损伤
小鼠
药物毒性
吉西他滨
Radation injuries, experimental
Lung injuries, mouse
Drug toxicity, gemcitabine
