巴豆醛亚慢性染毒致雄性大鼠肺部炎症反应作用机制  

Mechanism of sub-chronic crotonaldehyde exposure-induced pulmonary inflammation in male rats

作　　者：李双双 张淑曼 陈克川 张彪[1,2] 赵玉军 张志虎[2,4] LI Shuangshuang;ZHANG Shuman;CHEN Kechuan;ZHANG Biao;ZHAO Yujun;ZHANG Zhihu(School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan , Shandong 250062, China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,山东济南250062 [2]山东省医学科学院山东省职业卫生与职业病防治研究院,250062 [3]济南市急救中心,250021 [4]山东省第一医科大学,250062

出　　处：《中国职业医学》2019年第3期273-279,共7页China Occupational Medicine

基　　金：山东省自然科学基金(ZR2016YL016)

摘　　要：目的观察巴豆醛亚慢性染毒致雄性大鼠肺部炎症反应、氧化应激与细胞凋亡情况,探讨其相关机制。方法将无特定病原体级雄性Wistar大鼠随机分为对照组和低、中、高染毒组,每组10只,分别予剂量为0.0、2.5、4.5、8.5 mg/kg体质量的巴豆醛溶液灌胃染毒,每天1次,连续120 d。染毒结束后处死大鼠,称量肺脏质量并进行组织病理学检查,采用比色法测定大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平,采用荧光探针检测肺组织中活性氧相对表达水平,采用Tunel染色法检测细胞凋亡率,采用免疫印迹法检测肺组织B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白的相对表达水平。结果与同时间点对照组比较,高剂量组大鼠体质量于染毒30 d开始出现下降(P<0.05),低、中剂量组大鼠体质量于染毒90 d开始出现下降(P<0.05);高剂量组大鼠体质量于染毒90 d起分别低于低、中剂量组(P<0.05)。染毒结束后,3个剂量组大鼠肺组织出现不同程度的肺组织炎症性改变,呈剂量-效应关系。大鼠血清MDA水平随巴豆醛染毒剂量升高而升高(P<0.01),SOD和GSH-Px活力均随巴豆醛染毒剂量升高而下降(P<0.01)。大鼠肺组织中活性氧相对表达水平和细胞凋亡率均随巴豆醛染毒剂量升高而升高(P<0.01),Bcl-2蛋白相对表达水平和Bcl-2/Bax比值均随巴豆醛染毒剂量升高而下降(P<0.01),Bax和Caspase-3蛋白相对表达水平随巴豆醛染毒剂量升高而升高(P<0.01)。结论巴豆醛亚慢性染毒通过改变大鼠肺组织氧化平衡状态,导致肺组织细胞凋亡,从而引起肺部炎症性病理改变。Objective To observe the conditions of sub-chronic crotonaldehyde exposure-induced pulmonary inflammation,oxidative stress and apoptosis in male rats,and to explore the related mechanisms. Methods The specific pathogen free Wistar male rats were randomly divided into control group,low-,medium-and high-dose crotonaldehyde groups,with 10 rats in each group. Rats were treated with crotonaldehyde at the concentrations of 0. 0,2. 5,4. 5 and 8. 5 mg/kg body weight by intra-gastric administration,once per day for 120 consecutive days. After the end of treatment,rats were sacrificed,the lungs were weighed and histopathological examination was performed. The levels of malondialdehyde( MDA),superoxide dismutase( SOD) and glutathione peroxidase( GSH-Px) in the serum of rats were determined by colorimetry. The relative expression of reactive oxygen species in lung tissues was detected by fluorescence probe. The apoptosis rate was detected by Tunel staining. The relative expression of B-cell lymphoma( Bcl)-2,Bcl-2 associated X protein( Bax) and cysteine aspartic acid protease-3( Caspase-3) proteins in lung tissue was detected by western blotting.Results The body weight of the rats in the high-dose group began to decrease after 30 days of exposure( P < 0. 05),and the body weight in the low-and medium-dose groups began to decrease at 90 days exposure( P < 0. 05),when compared with that of the control group at the same time. The body weight of the high-dose group was lower than that of the low-and medium-dose groups began to decrease at 90 days exposure( P < 0. 05). After exposure,the lung tissue of the three doses groups showed different degrees of inflammatory change in a dose-effect relationship. The level of serum MDA in rats increased with the treatment of crotonaldehyde( P < 0. 01). The activities of serum SOD and GSH-Px decreased with the treatment of crotonaldehyde( P < 0. 01). The relative expression of ROS and apoptosis rate in rat lung tissue increased with the treatment of crotonaldehyde( P < 0. 01). The relative exp

关 键 词：巴豆醛 肺 炎症 氧化应激 细胞凋亡 大鼠 

分 类 号：R114[医药卫生—卫生毒理学] R135.1[医药卫生—公共卫生与预防医学]