自噬体及凋亡小体对新生小鼠支气管肺发育不良调控作用

目的探究自噬体及凋亡小体对新生小鼠支气管肺发育不良（bronchopulmonary dysplasia，BPD）调控作用。 方法新生SD小鼠36只随机分为对照组、模型组、干预组，每组12只，对照组置于空气中，模型组、干预组置于封闭氧箱中（氧浓度维持在60%）以制备BPD模型，干预组小鼠从造模开始给予自噬抑制剂（氯喹）20 mg/kg腹腔注射，1次/d，连续21 d。22 d时观察各组小鼠一般情况，采用HE染色观察各组小鼠肺组织病理变化，透射电镜下观察各组小鼠肺泡Ⅱ型上皮细胞超微结构，采用Western Blot检测肺组织中自噬相关蛋白［P62、微管相关蛋白轻链3B（microtubule associated protein light chain 3B，LC3B）］及凋亡相关蛋白［Bcl-2相关X蛋白(Bax)、半胱氨酸天冬氨酸蛋白酶3（Caspase-3）］表达水平。 结果干预组小鼠精神状态、毛发生长、饮食情况、呼吸情况、体重等较模型组明显好转，未出现死亡小鼠。干预组小鼠肺组织病理改变较模型组明显改善，肺泡Ⅱ型上皮细胞胞浆中自噬体及凋亡小体数量较模型组明显减少。模型组小鼠肺组织中LC3B、P62、Bax、caspase-3水平显著高于对照组（P＜0.05）；干预组小鼠肺组织中LC3B、P62、Bax、caspase-3水平显著低于模型组（P＜0.05）；干预组小鼠肺组织中LC3B、P62、Bax、caspase-3水平显著高于对照组（P＜0.05）。 结论新生小鼠肺泡Ⅱ型上皮细胞自噬过度活化后自噬体增多，促进肺泡Ⅱ型上皮细胞大量凋亡，凋亡小体增加，从而导致BPD发生，这可为BPD预防和治疗提供理论支持。

Regulation of autophagosomes and apoptotic bodies on bronchopulmonary dysplasia in neonatal mice

ObjectiveTo investigate the regulation effect of autophagosomes and apoptotic bodies on bronchopulmonary dysplasia(BPD) in neonatal mice.MethodsThirty-six neonatal SD mice were randomly and equally divided into three groups for different treatments, control group, model group and intervention group. On the 22nd day, the general situation of mice in each group was observed, the pathological changes of lung tissue were observed by HE staining, and the ultrastructure of type Ⅱ alveolar epithelial cells in each group was observed by transmission electron microscopy. The expression levels of autophagy related proteins ［P62, microtubule-related protein light chain 3B(LC3B)］ and apoptotic related proteins ［Bcl-2-related X protein(Bax), caspase-3］ in lung tissues were detected by Western blot.ResultsCompared with the model group, the mental state, hair growth, diet, breathing and body weight of the mice in the intervention group were significantly improved, with no mice died. Moreover, the pathological changes of lung tissue in the intervention group were also significantly improved. The number of autophagosomes and apoptotic bodies in the cytoplasm of type Ⅱ alveolar epithelial cells in the intervention group was significantly lower than that of the model group. The levels of LC3B, P62, Bax and caspase-3 in the lung tissue among three groups were the highest in the intervention group, followed by model group and control group, with statistic difference(P＜0.05).ConclusionAfter excessive autophagy activation of type Ⅱ alveolar epithelial cells in newborn mice, autophagosomes are increased, which promotes a large number of apoptosis of type Ⅱ alveolar epithelial cells and increases the apoptotic corpuscles, thus leading to the occurrence of bronchopulmonary dysplasia, so it can provide theoretical support for the prevention and treatment of BPD.