血必净注射液对硫化氢急性中毒大鼠肺组织氧化应激及Nrf2基因表达的干预作用  

Effect of Xuebijing on Oxidative Stress and Nrf2 Expression in the Lung Tissue of Acute H2S-intoxicated Rats

作　　者：葛赟 卢中秋[2] 洪广亮[2] 姜小珍[2] 刘瑶[2] 胡国新[3] 邱俏檬[2] 

机构地区：[1]杭州市滨江医院急诊科,310000 [2]温州医学院附属第一医院急诊科,325000 [3]温州医学院药学院

出　　处：《医学研究杂志》2012年第12期69-73,共5页Journal of Medical Research

基　　金：浙江省医学创新学科建设计划项目(11-CX26);浙江省医学扶植重点学科(07-F04);浙江省中医药科学研究基金资助项目(2010ZA086)

摘　　要：目的探讨硫化氢(hydrogen sulfide,H2S)急性中毒大鼠肺组织氧化应激水平及核转录因子红系相关因子-2(nu-clear factor E2-related factor 2,Nrf2)的改变及血必净注射液(XBJ)对其的影响。方法将清洁级SD大鼠96只随机分为正常对照组(n=8),XBJ对照组(n=8),H2S染毒组(n=40)和XBJ干预组(n=40)。化学比色法检测肺组织中丙二醛(MDA)浓度、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化氢酶(GSH-Px)活力及谷胱甘肽(GSH)含量,RT-PCR法检测Nrf2的基因表达,观察肺组织病理学改变。结果与正常对照组比较,H2S染毒组大鼠肺组织在2、6、12h SOD、CAT活力和GSH含量及在2、6、12、24h GSH-Px活力明显降低(P<0.01或P<0.05),在2、6、12、24h MDA含量明显升高(P<0.01)。与H2S染毒组比,XBJ干预组大鼠肺组织在2、6、12h CAT活力和GSH含量及在2、6、12、24h SOD和GSH-Px活力明显升高(P<0.01或P<0.05),在2、6、12h的MDA含量明显降低(P<0.01或P<0.05)。H2S染毒组肺组织大鼠肺组织在2、6、12h Nrf2 mRNA表达(0.240±0.012,0.167±0.011,0.146±0.010)明显高于正常对照组(0.130±0.009)(P<0.01或P<0.05);与H2S染毒组比,XBJ干预组大鼠肺组织在6、12、24、48h Nrf2 mRNA表达(0.244±0.008,0.279±0.013,0.349±0.012,0.257±0.008)明显升高(P<0.01)。光镜下,H2S染毒组在24 h肺组织损害明显,XBJ干预组肺损伤较H2S染毒组有所减轻。结论氧化应激损伤是H2S中毒急性肺损伤主要机制之一,XBJ可上调Nrf2的基因表达,抑制氧自由基产生,纠正氧化还原失衡,对肺脏起保护作用。Objective To investigate the dynamic changes of oxidative stress and Nuclear factor - E2 - related factor2 expression in the lung tissue of acute H2S - intoxicated rats and study the intervention effects of Xuebijing（ XBJ）. Methods A total of 96 SD rats of clean grade were divided randomly into four groups ： normal control group （ n = 8 ） , XBJ control group （ n = 8 ） , H2 S - intoxicated model group （ n = 40 ）, and XBJ treatment group （ n = 40 ）. The levels of malondialdehyde （ MDA ）, superoxidedismutase （ SOD）, catalase （ CAT）, glutathioneperoxidase （ GSH - Px） and glutathione （GSH） in the lung tissue were measured, and the expression of Nrf2 mRNA in the lung tissure was detected. Pathological changes of lung tissue were observed by lightmicroscope. Results The pulmonary SOD, CAT and GSH levels at 2,6,12h（P 〈0.01） and the pulmonary GSH - Px level at 2,6,12,24h（P 〈0.01 or P 〈0.05） in rats of H2S - intoxicated mod- el group after modeling were markedly decreased than that in normal control group. The level of pulmonary MDA in rats of H2S -intoxica- ted model group at 2,6,12,24h（ P 〈 0.01 ） after modeling were markedly increased than that in normal control group. In comparison with H2S - intoxicated model group, the pulmonary CAT activity and GSH level at 2,6,12h（P 〈0.01 or P 〈0.05） , and the pulmonary SOD and GSH - Px activity at 2,6,12,24h（ P 〈 0.01 ） in rats of XBJ treatment group increased. The pulmonary MDA level in rats of UTI treat- ment group decreased at 2,6,12h（ P 〈 0.01 or P 〈 0. 05 ）. The expression of Nrf2 mRNA in rats of H2 S -intoxicated model group at 2,6, 12h（0. 240±0.012,0. 167±0. 011,0. 146±0.010） （P 〈0.01 or P 〈0.05） after modeling were markedly increased than that in normal control group（0. 130±0. 009）. In comparison with HzS - intoxicated model group, the expression of Nrf2 mRNA in rats of XBJ treatment group increased at 6,12,24,48 h （0. 244±0. 008,0. 279±0.013,0. 349±0.012,0. 257±0.

关 键 词：硫化氢 血必净注射液 氧化应激 核转录因子红系相关因子-2 大鼠 

分 类 号：R595.1[医药卫生—内科学]