论文部分内容阅读
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 observe the effects of different administration of gemcitabine on radiation-induced lung injury in rats and to explore its molecular mechanism. Methods Male BALB / C mice weighing about 25 g were randomly divided into blank control group (C), radiation group (R), administration group (G) Simultaneous administration (R + CG) group, each group 80. Experimental observation of a total of 8 months. Using 6MVX line irradiation, irradiation area 2.0cm × 2.5cm, irradiation dose 25Gy points 5 times. Gemcitabine dose of 80mg / (kg · d), the first 1,5 days of intraperitoneal administration. G group after the first month after administration, counting the total number of inflammatory cells and classification by microscope. Left lung tissue was taken monthly for hydroxyproline content and pathological examination. The right lung was used for immunohistochemical analysis of TGF-β1, EGF and ICAM-1. 100 μl of plasma was taken from the sacrificed mouse heart every month for detection of TGF-β1, EGF and ICAM-1. Results Gemcitabine was predominantly inflammatory exudate (> 90% of neutrophils) in the early stage of lung injury. Exudation, hyperplasia and fibrosis were the major components of gemcitabine at 1, 3 and 6 months after the experiment. The content of hydroxyproline in R + CG group was significantly higher than the other groups (P <0.01) at the 5th month and continued until the end. The plasma ICAM-1 level in R + CG group was significantly higher than that in other groups at the first month after irradiation (P <0.01), and began to decline after the second month. The plasma levels of EGF in R + CG group were significantly higher than those in the other groups at the second and third month after irradiation (P <0.01), and began to decrease after the fourth month. The content of TGF-β1 in the R + CG group was significantly higher than that of other groups at the third month Group (P <0.01), after the content is relatively stable. The expression of ICAM-1 in R + CG group was significantly higher than that in other groups at the first month (P <0.01), and began to decrease after the second month. The expression of EGF in the R + CG group was significantly higher than that in other groups <0.01), and began to decrease after the 4th month. The expression of TGF-β1 in the third month was significantly higher than that in other groups (P <0.01). Conclusions The pathological histology and the content of hydroxyproline, TGF-β1, EGF, ICAM-1 and immunohistochemical analysis can significantly increase the incidence of radiation-induced lung injury with concurrent administration of gemcitabine and irradiation.