卡托普利在高氧致新生大鼠肺损伤模型中的保护作用

Protective effects of captopril on hyperoxia-induced lung injury in neonatal rats

摘要:

目的：观察卡托普利对高氧暴露新生大鼠支气管肺泡灌洗液(BALF)及肺组织形态学改变的影响。方法：足月新生Wistar大鼠40只生后即置于有机玻璃氧舱内持续吸入高浓度氧(FiO2=0.90)14d、21d造成高氧肺损伤模型,治疗组经胃管灌服卡托普利每日60mg/kg(用生理盐水配成5.4mg/mL混悬液),对照组每天经胃管灌服等量生理盐水,空气对照组:吸入空气(FiO2=0.21)。对4组大鼠进行肺系数、BALF中蛋白含量及BALF细胞计数和分类测定并同步观察肺组织形态学的改变。结果：模型组及盐水对照组14d,21d肺系数、BALF中蛋白含量、BALF细胞总数、中性粒细胞、淋巴细胞和嗜酸性粒细胞比例较空气对照组显著升高(P<0.01)。卡托普利治疗组与模型组比较上述指标(除淋巴细胞外)均显著下降(P<0.05或P<0.01);与空气对照组比较亦有统计学差异,P<0.05。模型组及盐水对照组14d,21d肺组织学表现为不同程度的肺泡炎、肺泡间隔增宽、肺泡融合、肺泡数量减少;而卡托普利治疗组肺组织病变明显减轻。结论：卡托普利对高氧所致肺损伤具有一定的保护作用。

Abstract:

OBJECTIVE: To study the effect of captopril on the histopathology and bronchoalveolar lavage fluid (BALF) in neonatal rats exposed to hyperoxia. METHODS: Forty term neonatal Wistar rats were randomly assigned into Air control, Model, Normal saline control and Captopril-treated groups (n=10 each). The Air control group was exposed to air ( FiO-2=0.21). The remaining three groups were continuously exposed to hyperoxia (FiO-2=0.90). During exposure the Captopril-treated group received intragastric captopril (60 mg/kg daily) and the Normal saline control group was administered with normal saline. The Model group had no treatment. At the 14th and 21st days of exposure, the subjects were sacrificed. The lung coefficient and the protein contents and inflammatory cells in BALF were determined. The changes of lung histomorphology were observed. RESULTS: The lung coefficient and the protein contents, the total number of cells and the percentage of neutrophils, lymphocytes and eosinophils in BAFL increased significantly in the Model and Normal saline control groups on the 14th and 21st days of exposure compared with those of the Air control group. Captopril treatment significantly reduced the lung coefficient and the protein contents, the total number of cells and the percentage of neutrophils and eosinophils in BALF. On the 14th day the lung coefficient decreased from 9.72±0.67 mg/g to 8.63± 0.35 mg/g (P<0.05); the protein contents in BALF from 0.619±0.023 g/L to 0.486±0.027 g/L (P<0.05); and the total number of cells in BALF from (80.57±9.28)×104/mL to (48.62±1.53)×104/mL (P<0.01) compared with the Model group. On the 21st day the lung coefficient decreased from 10.67±0.87 mg/g to 8.76±0.89 mg/g (P<0.05); the protein contents in BALF from 0.978±0.012 g/L to 0.759±0.042 g/L (P<0.05); and the total number of cells in BALF from (92.86±10.32) ×104/mL to (35.52±3.89) ×104/mL (P<0.05) compared with the Model group. There were however significant differences in these results between the Captopril-treated and Air control groups. The histopathological examination demonstrated different degrees of alveolitis, broaden interstitium and reduced alveolar quantity in the Model and Normal saline control groups. The pathological changes were markedly alleviated after captopril treatment. CONCLUSIONS: Captopril may have protective effects on lung injury induced by hyperoxia .