N-乙酰半胱氨酸对高氧性肺损伤新生未成熟大鼠肺纤维化的抑制作用  

The inhibiting effect of N-acetylcysteine on pulmonary fibrosis caused by hyperoxia induced lung injury in newborn premature rats

作　　者：周晓光[1] 刘秀香[2] 刘仁红 肖昕[2] 熊爱华[4] 

机构地区：[1]广州医学院第二附属医院新生儿科,510260 [2]暨南大学第一医院新生儿科 [3]深圳市宝安区沙井人民医院儿科 [4]暨南大学药学院实验中心

出　　处：《中国新生儿科杂志》2007年第1期31-35,I0003,共6页Chinese Journal of Neonatology

基　　金：广州医学院科学研究基金项目(2003-016);暨南大学自然科学基金项目(620008)

摘　　要：目的 探讨高氧性肺损伤新生未成熟大鼠肺纤维化过程中Ⅰ、Ⅲ型胶原的沉积情况，并观察N-乙酰半胱氨酸（NAC）的干预效果，以期为临床防治高氧性肺损伤后肺纤维化提供一条新的有效途径。方法 将200只孕21d（足月为22～23d）剖宫产出生的新生SD大鼠随机分为空气组（Ⅰ组）、高氧组（Ⅱ组）、高氧＋生理盐水（NS）组（Ⅲ组）、高氧＋小剂量NAC组（Ⅳ组）、高氧＋大剂量NAC组（Ⅴ组）共5个组，每组40只。每组又随机分为3d、7d、14d和21d共4个亚组，每个亚组10只。Ⅰ组在空气中饲养；Ⅱ、Ⅲ、Ⅳ、Ⅴ组置于同一室的高浓度氧（〉95％）箱中饲养；Ⅳ、Ⅴ组大鼠以灌胃方式给予NAC（大剂量组每天给予6．25×10^-5gNAC／g体重，小剂量组是大剂量的1／4）；Ⅲ组给予相同容量的NS。光镜观察各组大鼠肺组织病理形态学；应用图像分析方法检测肺组织Ⅰ、Ⅲ型胶原的含量，并比较各组大鼠肺组织Ⅰ、Ⅲ型胶原含量的差别。结果 3、7d时各组犬鼠肺组织Ⅰ型胶原免疫组化PU值的差异均无统计学意义（P均〉0．05）；14、21d时Ⅱ组较Ⅰ组明显增高（P均〈0．01），Ⅴ组则较Ⅱ组明显降低（P分别为0．015、0．001）。3d时各组大鼠肺组织Ⅲ型胶原免疫组化PU值的差异无统计学意义（P〉0．05）；7、14、21dⅡ组较Ⅰ组显著增加（P均〈0．01），Ⅴ组则显著低于Ⅱ组（P均〈0．01）。对各时间点Ⅳ组与Ⅱ组Ⅰ、Ⅲ型胶原的表达量之间进行比较，差异均无统计学意义（P〉0．05）。结论 高氧性肺损伤新生未成熟大鼠肺纤维化过程中Ⅰ、Ⅲ型胶原沉积增加，NAC对高氧性肺损伤后肺纤维化具有抑制作用，其作用具有剂量依赖性。Objective To study the deposition of collagen Ⅰ and Ⅲ in hyperoxia induced lung injury in newborn premature rats and to observe the interfering effect of N-acetylcysteine （ NAC ） on it. Methods Two hundred premature newborn SD rats（21-day gestational age） were randomly divided into air group （group Ⅰ）, hyperoxia group （group Ⅱ ）, hyperoxia with normal saline （NS） group （ group Ⅲ）, hyperoxia with low dose NAC group （group Ⅳ） and hyperoxia with high dose NAC group （group Ⅴ）. Each group had 40 rats and they were randomly divided into the 3^rd ,7^th 14^th ,21^th day subgroups. The rats in group I were fed in room air, group Ⅱ ,Ⅲ, Ⅳ and Ⅴ were fed in 95% oxygen chambers. The rats in group Iv and Ⅴ received NAC via gastric tube with the high dose of 6. 25 × 10 ^-5 g/g weight or the low dose of 1.56×10^-2 g/g weight. The rats in group Ⅲ received NS via gastric tube too. The rats of each group were sacrificed respectively at above given time. The histopathology of lung tissue was observed analysis. compared by light microscope. The levels of collagen Ⅰ and Ⅲ in lung tissues were measured by image The differences of collagen Ⅰ and Ⅲ in lungs among group Ⅰ , Ⅱ, Ⅲ, Ⅳ and Ⅴ were Results On the 3^rd and 7^th day , there was no difference of the expression of collagen Ⅰ in each groups（P 〉 0.05）. On the 14th and 21st day, the expression of collagen Ⅰ in group Ⅱ was significantly higher than that of group Ⅰ （P 〈0. 01 ）and group Ⅴ （P =0. 015, O. 001 ）. On the 3^rd day, the expression of Collagen Ⅲ was same in all groups（P 〉0. 05）, but on the 7^th, 14^th and 21^st day; its expression was significant higher in group Ⅱ than that of group Ⅰ and group Ⅴ （ P 〈 0. 01 ）. Comparing group Ⅱ and group Ⅳ, the levels of collagen Ⅰ and Ⅲ had no statistical significance during the course. Conclusions The deposition of collagen Ⅰ and Ⅲ increases during pulmonary fibrosis caused by hyperoxia induced lung injury i

关 键 词：乙酰半胱氨酸 高氧症 肺纤维化 大鼠肺组织 

分 类 号：R722.1[医药卫生—儿科]