【摘要】 目的观察水通道蛋白4（AQP4）基因敲除对博莱霉素（BLM）致小鼠肺纤维化过程的影响,初步评价半胱氨酰白三烯受体在此过程的作用。方法设AQP4^+/+对照组、AQP4^+/+BLM组、AQP4^-/-对照组、AQP4^-/-BLM组,每组各6只小鼠。每日记录一般情况,第12天处死小鼠,算肺系数及HE、Masson染色观察病理变化,提取蛋白行免疫印迹杂交（Western blotting）检测半胱氨酰白三烯受体1（Cys LT₁R）、受体2（Cys LT₂R）的表达。结果第12天时,AQP4^+/+BLM组小鼠肺系数（14.65±1.92）为AQP4^+/+对照组（6.97±1.54）的2.1倍（P<0.01）,AQP4^+/+BLM组的Cys LT₁R表达明显高于AQP4^+/+对照组（P<0.05）,而Cys LT₂R表达稍低于AQP4^+/+对照组,但差异无统计学意义（P>0.05）。第12天时,AQP4^-/-BLM组小鼠肺系数（10.99±1.66）为AQP4^-/-对照组（6.19±2.09）的1.8倍（P<0.01）,AQP4^-/-BLM组的Cys LT₁R、Cys LT₂R表达与AQP4^-/-对照组比较,差异无统计学意义（P>0.05）。AQP4^-/-BLM组肺系数明显低于AQP4^+/+BLM组,差异有高度统计学意义（P<0.01）。肺组织病理学结果表明AQP4^-/-BLM组小鼠炎症细胞浸润及纤维化程度较AQP4^+/+BLM组轻。结论 AQP4基因敲除可减轻博莱霉素诱导的小鼠肺纤维化过程中的肺水肿、肺泡炎,AQP4可能是通过调控Cys LT₁R参与此过程。更多还原

【Abstract】 Objective To observe the effects of aquporin-4 and Cysteinyl leukotriene receptor on Bleomycin（BLM） induced pulmonary fibrosis in mice. Methods The experiment was divided into AQP4^+/+control group, AQP4^+/+BLM group, AQP4^-/-control group and AQP4^-/-BLM group, with 6 mice in each group. General status of mice were recorded every day, The mice were sacrificed on the 12 th day and the pulmonary index was calculated. HE and Masson’s staining were administered to observe the pathological changes. The expression of Cys LT₁receptor（Cys LT₁R） and Cys LT₂receptor（Cys LT₂R） were observed by Western blotting. Results At the 12 th day, the lung coefficient of AQP4^+/+BLM group（14.65±1.92） was 2.1 times as much as AQP4^+/+control group（6.97±1.54）（P < 0.01）, the level of Cys LT₁ receptor expression in AQP4^+/+BLM group was higher than that in AQP4^+/+control group（P < 0.05）, Cys LT₂ R expression was slightly lower, but the differences were not statistically significant（P > 0.05）. At the 12 th day, the lung coefficient of AQP4^-/-BLM group（10.99±1.66） was 1.8 times as much as AQP4^-/-control group（6.19±2.09）（P < 0.01）, Cys LT₁ R and Cys LT₂ R expression in AQP4^-/-BLM group was compared with AQP4^-/-control group, the differences were not statistically significant（P > 0.05）. the lung coefficient of AQP4^-/-BLM group was lower than that in AQP4^+/+BLM, the differences were statistically significant（P < 0.05）. Pathological examination results of lung tissues indicated that the effect of reducing alveolar catarrh and pulmonary fibrosis of AQP4^-/-BLM group had an advantage over that of AQP4^+/+BLM group. Conclusion AQP4 gene knockout can attenuate the degree of Bleomycin induced pulmonary edema, alveolar inflammation, AQP4 may regulate bleomycin induced lung fibrosis via Cys LT₁ R.更多还原