高温相关丝氨酸蛋白酶A2抑制剂Ⅰ对早产鼠高体积分数氧肺损伤的保护作用  

Protective Effect of High Temperature Requirement A2 Inhibitor Ⅰon Lung Injury Induced by Hyperoxia in Premature Rats

作　　者：何娜[1] 孙鸿燕[2] 董文斌[1] 李清平[1] 罗鹏[1] 卢美燕[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 [2]泸州医学院护理学院.卫校,四川泸州646000

出　　处：《实用儿科临床杂志》2012年第20期1585-1588,共4页Journal of Applied Clinical Pediatrics

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

摘　　要：目的研究高温相关丝氨酸蛋白酶A2(Omi/HtrA2)特异性抑制剂(Ucf-101)对早产鼠高体积分数氧(高氧)肺损伤的保护作用。方法 72只新生早产Wistar大鼠在出生12 h随机分为对照组、高氧组、高氧+Ucf-101组,每组24只。高氧+Ucf-101组新生大鼠高氧暴露前10 min,按1.5μmol·kg-1腹腔注射Ucf-101,对照组和高氧组新生大鼠在相同时点注射等量的9 g·L-1盐水;高氧组和高氧+Ucf-101组新生大鼠持续暴露于950 mL·L-1氧气中,对照组新生大鼠置于同一室内常压空气中。分别于暴露1 d、3 d、7 d时,每组取动物8只,留取肺组织标本。左肺制作石蜡切片,采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结法检测Omi/HtrA2、X连锁凋亡抑制蛋白(XIAP)和半胱氨酸天冬氨酸蛋白酶-9(Caspase-9)在各组肺组织的表达;采用原位末端标记法检测肺细胞凋亡情况。右肺制作冷冻切片,采用间接免疫荧光双染色法,在激光共聚焦显微镜下观察Omi/HtrA2在细胞内的转位。结果 1.高氧组和高氧+Ucf-101组肺组织Omi/HtrA2、Caspase-9随着高氧暴露时间延长表达量呈增高趋势,与对照组比较差异有统计学意义(Pa<0.05);高氧+Ucf-101组与高氧组比较,Omi/HtrA2、Caspase-9在同一时间点表达量明显降低,差异均有统计学意义(Pa<0.01)。高氧组和高氧+Ucf-101组XIAP较对照组明显减少,差异有统计学意义(P<0.01);高氧+Ucf-101组各时间点XIAP的表达量均显著高于高氧组,差异有统计学意义(P<0.01)。2.与对照组比较,高氧组和高氧+Ucf-101组肺组织细胞凋亡率明显增加(P<0.01);高氧+Ucf-101组与高氧组比较,同一时间点凋亡率显著减低(P<0.01)。3.高氧组和高氧+Ucf-101组肺组织Omi/HtrA2胞内转位率明显高于对照组(P<0.01),高氧+Ucf-101组肺组织Omi/HtrA2转位率较同一时间点的高氧组明显降低,差异有统计学意义(P<0.01)。结论 Ucf-101可能通过减少Omi/HtrA2在肺细胞胞质中的表达和线粒体的转�Objective To explore the protective effect of specific inhibitor of high temperature requirement A2 （ Omi/Htr A2 ） on lung injury induced by hyperoxia in premature rats. Methods Seventy - two Wistar premature rats were randomly divided into control group, hy-peroxia group and hyperoxia ＋ Uef - 101 group. The rats in hyperoxia ＋ Ucf- 101 group were injected with Uef-101 （ 1.5 μmol · kg^-1 ） in-traperitoneally at 10 min before hyperoxia induction,the others were treated with the same dose of 9 g · L^-1 saline at the same time. The rats in hyperoxia group and hyperoxia ＋ Ucf - 101 group were exposed to 950 mL · L^-1 oxygen,while the rats in control group were exposed to air. The rats in each group were sacrificed at 1,3,7 days after being exposed to hyperoxia or air and the lung tissues were collected. Streptavidin - peroxidase immunohistochemistry was used to detect the expressions of Omi/HtrA2, X - linked inhibitor of apoptosis protein （XIAP） and Caspase-9 in the lung cells of each group, terminal transfer nick end labeling was used to detect the apoptosis of lung tissue cells and the translocation rate of Omi/HtrA2 was determined by indirect immunofluorescent double staining method and observed with laser confocal micro-scope. Results 1. The expressions of Omi/HtrA2 and Caspase - 9 of lung tissues both significantly increased in hyperoxia group and hyperoxia ＋ Ucf-101 group compared with those in control group （Pa 〈 0.05 ） , while the expressions of Omi/HtrA2 and Caspase-9 of lung tissues in hyperoxia ＋ Uef-101 group were lower than those in hyperoxia group（ P 〈 0.01 ）. The expression of MAP in control group was higher than that in the other groups（ P 〈 0.01 ） ,while the expression of XIAP in hyperoxia ＋ Uef - 101 group was significantly higher than that in hyperoxia group at the same time point （ P 〈 0.01 ）. 2. The apoptotie index of lung tissue cells were higher in hyperoxia group and hyperoxia ＋ Ucf-101 group than that in control group（P 〈 0.01 ） , wh

关 键 词：高体积分数氧 肺损伤 高温相关丝氨酸蛋白酶A2 Ucf-101 细胞凋亡 大鼠 早产 

分 类 号：R722.1[医药卫生—儿科]