博莱霉素与博莱霉素A5诱导小鼠肺组织损伤的差异

Different Damaging Effect of Bleomycin and Bleomycin-A5 on Lung Tissues

目的探讨静脉注射博莱霉素(BLM)和博莱霉素A5(BLM-A5)对小鼠肺组织损伤的不同作用。方法8周龄雌性C57BL/6小鼠49只,随机分为BLM组19只、BLM-A5组20只和对照组10只,分别经尾静脉一次性注射BLM 150 mg/kg、BLM-A5 150 mg/kg和生理盐水。观察每组小鼠体重、生存率,肺组织病理改变及肺组织羟脯胺酸的含量。结果①BLM组和BLM-A5组小鼠最低体重分别为静脉注射处置前的65.46%和66.87%,均较对照组明显降低(P值均小于0.001)。②BLM组、BLM-A5组和对照组小鼠的生存率分别为:43%、55%和100%。③BLM组小鼠注射处置后28 d,在胸膜下及血管周围形成广泛、稳定的间质纤维化病理改变,而BLM-A5组无明显纤维化形成。BLM组与BLM-A5组、正常组比较,肺纤维化病理评分均明显增高(P值均小于0.001)。④BLM-A5组和对照组注射处置后28 d,右肺羟脯氨酸含量分别为471.6±49.4 nmol和405.0±74.6 nmol,两组间无统计学差异。BLM组为978.4±106.1 nmol,与BLM-A5组、对照组比较分别存在显著性差异(P值均小于0.01)。结论静脉注射BLM与BLM-A5,对小鼠肺组织损伤的作用存在着明显的差异,BLM可导致肺间质形成广泛的纤维化,而BLM-A5仅引起轻微的肺组织损伤,不形成明显的间质纤维化。

Objective To study the difference of bleomycin and bleomycin-A5 induced lung tissue injury in mice. Methods Forty nine C57BL/6 mice （female, 8 wk of age, 17 to 20 g body weight） were randomly divided into BLM, BLM-A5 and control groups. The mice received injection of bleomycin （ 150 mg/kg）, bleomycin-A5 （ 150 mg/kg） and normal saline via the tail vein, respectively. The body weight, survival rate, pathological changes of lung tissues and hydroxyproline content in lung tissues were analyzed. Results （1） The mice of the BLM and BLM-A5 groups lost their body weight 34.54% and 33.13% after treatment, respectively, significantly decreased in comparison with that of the control group. （2） The survival rate of the BLM and BLM-A5 groups were 43% and 55%, respectively, significantly decreased in comparison with that of the control group （ 100% ）. （3） 28 days after drug injection, fibrosis was widely and stably formed in the subpleura and around blood vessels in the BLM-treated mice, but not in the BLM-A5 group. The pathological score of pulmonary fibrosis in the BLM group was significantly higher than that in BLM-A5 and control groups （both were P 〈 0.001 ）. （4） 28 days after injection, the hydroxyproline content in the lung tissue in the BLM, BLM-A5 and control groups were 978.4 ± 106.1 nmol, 471.6 ± 49.4 nmol and 405.0 ± 74.6 nmol, respectively. It was significantly increased in the BLM group than that in the BLM-A5 and control groups （ P 〈 0.01 ）. Conclusions There are significantly different effects of BLM and BLM-A5 on the process of lung tissue injury in mice. BLM induces widely spread pulmonary fibrosis, but BLM-A5 only causes mild pulmonary damage, and does not induce remarkable fibrosis.