线粒体ATP敏感钾通道对早产鼠高体积分数氧肺损伤的保护作用  

Protective Effect of Mitochondrial ATP-Sensitive Potassium Channel on Lung Injury Induced by Hyperoxia in Premature Rats

作　　者：卢美燕[1] 董文斌[1] 康兰[1] 李清平[1] 何娜[1] 罗鹏[1] 翟雪松[1] 雷小平[1] 

机构地区：[1]泸州医学院附属医院新生儿科,四川泸州646000

出　　处：《实用儿科临床杂志》2012年第18期1402-1405,共4页Journal of Applied Clinical Pediatrics

基　　金：中华儿科杂志第二届双鹤珂立苏科研基金;四川省教育厅科研基金(08ZA150);四川省卫生厅科研基金(90191)

摘　　要：目的探讨线粒体ATP敏感钾通道(mitoKATP)在早产鼠高体积分数氧(高氧)肺损伤中的保护作用。方法早产Wistar大鼠72只,随机分为对照组、高氧组和二氮嗪组。二氮嗪组在高氧暴露前30 min,按10 mg·kg-1腹腔注射二氮嗪,其余2组在相同时点腹腔注射等量9 g·L-1盐水,高氧组和二氮嗪组置于950 mL·L-1氧气中,对照组置于同一条件常压空气中。分别于空气或高氧暴露1 d、3 d、7 d时收集肺组织,HE染色观察其肺组织病理形态变化,原位末端标记法检测其肺组织细胞凋亡率,免疫组织化学法检测其肺组织Caspase-9和Omi/HtrA2的表达,激光共聚集显微镜下观察间接免疫荧光双染色Omi/HtrA2的胞内转位。结果与对照组比较,高氧组肺组织受损明显,形态改变,细胞凋亡率明显增加(P<0.01),Caspase-9、Omi/HtrA2表达增多(P<0.01),Omi/HtrA2胞内转位率明显增高(P<0.01)。与高氧组比较,二氮嗪组肺组织受损得到改善,细胞凋亡率减少(P<0.01),Caspase-9、Omi/HtrA2表达显著减少(Pa<0.01),Omi/HtrA2胞内转位率明显减少(P<0.01)。结论二氮嗪可能通过开放mi-toKATP减少Caspase-9和Omi/HtrA2的表达,减少Omi/HtrA2在细胞内的转位,从而减轻早产鼠高氧肺损伤。Objective To explore the protective effect of mitochondrial ATP - sensitive potassium channel（mitoKATP） on lung injury induced by hyperoxia in premature rats. Methods Seventy - two Wistar premature rats were randomly divided into control group, hyperoxia group and diazoxide group. The rats in diazoxide group, 30 minutes before hyperoxia exposure, received 10 mg · kg-1 diazoxide intraperitoneal injection,while the others were treated with the same dose of physiological saline at the same time. The rats in hyperoxia group and diazoxide group were exposed to 950 mL · L-ioxygen,while the rats in control group were exposed to air. The rats in each group were sacrificed after 1 day,3 days,7 days after hyperoxia induction and the lung tissues were collected. The histopathological change of the lungs was observed by means of HE staining. In situ end labeling was used to detect the apoptosis index of lung issue cell. The expressions of Caspase - 9 and Omi/ HtrA2 in lungs were evaluated by immunohistoehemistry. The translocation rate of Omi/HtrA2 was determined by indirect immunofluoreseenee and observed with laser focal microscope. Results Compared with control group,the hyperoxia group had obvious lung tissue injury,while the form change and the apoptosis rate of lung cells, the expression of Caspase - 9, Omi/ HtrA2, and the translocation rate of Omi/ HtrA2 were significantly increased（ P 〈 0.01 ）, but compared with the hyperoxia group, the morphology of lung tissue was obviously alleviated in the diazoxide group ,while the apoptosis rate of lung cells, the expression of Caspase -9, Omi/HtrA2, and the translocation rate of Omi/HtrA2 were significantly reduced in the diazoxide group （P, 〈 0.01 ）. Conclusions Diazoxide could relieve the lung injury induced by hyperoxia via activating the mitoKATP, reducing the expression of Caspase -9 and Oml/HtrA2, and inhibiting the transloeation of Omi/HtrA2 from mito- chondria in premature rats.

关 键 词：高体积分数氧 肺损伤 二氮嗪 凋亡 大鼠 早产 

分 类 号：R722.6[医药卫生—儿科]