紫杉醇加重放射性肺损伤的实验研究

Paclitexel accentuates irradiation-induced pulmonary injuries

目的用小鼠肺损伤模型模拟临床治疗进行照射加紫杉醇致肺损伤的研究, 对不同结合方式的损伤模式进行探索.方法小鼠分正常对照组、单用紫杉醇(CT)组、单纯照射(R T)组、紫杉醇后10 d加照射(CT+RT)组、照射后10 d加紫杉醇(RT+CT)组和照射紫杉醇同步(CRT)组.用6 MV X线照射小鼠全肺21 Gy分5次5 d完成,用紫杉醇30 mg/kg腹腔注射,2次/ 周.观察指标为肺泡灌洗液蛋白含量和细胞数变化、小鼠死亡、血性胸水、肺泡壁肿胀和细胞浸润及肺纤维化积分,设实验后第1～6个月6个观察点.结果照射加紫杉醇3个组(CT+RT 、RT+CT、CRT组)与RT组小鼠肺损伤死亡比例分别占15/54、17/54、19/54与10/54,死亡时间和出现胸水均提前1个月.照射加紫杉醇3个组肺泡灌洗液蛋白含量和细胞总数均在第4、5 个月也明显高于RT组;肺纤维化积分也从第3个月开始比RT组高,以第4个月最高.照射加紫杉醇3个组以上各观察指标的差别均不明显.CT组第1个月肺泡灌洗液蛋白含量和细胞总数、肺泡壁肿胀与炎性细胞浸润比对照组也稍高,持续2个月以上,未发生明显肺纤维化.结论单纯紫杉醇可致较轻肺组织损伤,而紫杉醇与照射结合可加重肺组织的放射性损伤.

Objective To study the mechanism of pulmonary toxicity accentuated by paclitexel, using the model of irradiation induced pulmonary injury in mice. Methods Six groups- control, paclitexel alone（CT）, radiation alone （RT）, 10 days after paclitexel radiation was given（CT ＋ RT）, 10 days after radiation paclitexel was given（RT ＋ CT）, and conccurrent radiation and paclitexel（CRT）, were entered into the study. For radiation, 21 Gy/Sf/Sd was given to the whole lung. Paclitexel 30 mg/kg was infused into the peritoneal cavity twice a week. The mortality of mice, pleural effusion, presence of protein and cell count in the bronchoalvealar lavage （BAL） and pulmonary fibrosis were monitored every month, till the to 6th month. Results There was higher mortality and earlier mortality during the first month in the three groups which received both radiation and paclitexel（CT ＋ RT, RT ＋ CT, CRT） than in radiation alone（RT）. Their pulmonary injury rate mortality rate were 15/54, 17/54, 19/54 and 10/54,respectively. The time of death and development of pleural effusion were all 1 month earlier in the combined group as compared with RT alone group. The presence of higher incidence of protein and cells in the bronchoalvealar lavage （BAL） were observed in these three groups in the 3rd and 4th month as compared with the RT alone group, especially in the 4th month. Similar differences were also observed for pulmonary fibrosis 4 months after radiation. However, these differences were not of statistical significance. More swelling and abundant cells in the septa and presence of more protein and cells in BAL were found in the paclitexel alone group as compared with the control group, still without any significance. Conclusions It is shown that this study shows paclitexel could accentuate radiation-induced acute and late pulmonary injuries. Injuries induced by paclitexel may be mild, however, it becomes important when radiation is added.