硫化氢对脂多糖诱导大鼠肺动脉反应性和损伤的影响  

Effect of hydrogen sulfide on rat pulmonary artery reactivity and injury induced by lipopolysaccharide

作　　者：张晓静[1] 黄新莉[2] 孟祥艳[3] 丛斌[1] 戴鸿雁[2] 韦鹏[2] 凌亦凌[2] 

机构地区：[1]河北医科大学基础医学院法医学系,石家庄050017 [2]河北医科大学基础医学院基础医学院病理生理学教研室,石家庄050017 [3]武警医学院病理生理学教研室

出　　处：《中国危重病急救医学》2010年第8期465-468,共4页Chinese Critical Care Medicine

基　　金：国家自然科学基金资助项目（30800440）;河北省自然科学基金资助项目（C2007000830,c2008001040）

摘　　要：目的 观察硫化氢（H2S）对脂多糖（LPS）所致肺动脉反应性紊乱和肺动脉损伤的影响.方法 72只SD大鼠按随机数字表法分为对照组、LPS组、H2S供体硫氢化钠（NaHS）＋LPS组和NaHS＋生理盐水（NS）组,每组18只.采用气管内滴注0.8 ml/kg LPS（200 μg/200 μl）染毒.滴注LPS之前10 min和之后2 h分别经腹腔注射0.5 ml NaHS（28 μmol/kg）.实验12 h处死大鼠,取颈动脉血,检测血清H2S含量;制备肺动脉环（PARs）,采用离体血管环张力测定技术检测血管反应性变化;检测肺动脉丙二醛（MDA）含量,并观察肺动脉形态学改变.结果 与对照组相比,滴注LPS后,PARs对苯肾上腺素（PE,10^-6 mol/L）的收缩反应（g/mg）明显升高（0.86±0.20比0.56±0.13）,对乙酰胆碱（ACh,10^-6 mol/L）的舒张反应明显降低[（65.18±7.05）%比（84.13±8.84）%],肺动脉组织MDA含量（mmol/L）升高（32.03±7.81比5.82±0.92）,血清中H2S含量（μmol/L）降低（175.23±27.36比238.12±16.38）,差异均有统计学意义（P〈0.05或P〈0.01）;组织形态学观察显示,肺动脉内皮细胞和组织结构严重受损.给予NaHS后可明显改善LPS引起的上述变化,血管收缩反应下降[（0.61±0.17） g/mg],血管舒张反应升高[（82.92±9.71）%],肺动脉组织MDA含量下降[（16.88±3.54） mmol/L],血清H2S含量升高[（242.70±38.80） μmol/L],差异有统计学意义（P〈0.05或P〈0.01）;肺动脉内皮细胞和组织结构损伤也得到明显改善.NaHS＋NS组除H2S含量显著高于对照组外,余指标与对照组比较差异无统计学意义.结论 外源性应用H2S不仅可逆转LPS引起的肺动脉反应性紊乱,还可减轻LPS引起的肺动脉组织损伤.Objective To explore the effects of hydrogen sulfide （H2S） on abnormal pulmonary artery reactivity and injury induced by lipopolysaccharide （LPS）. Methods Seventy-two rats were divided into four groups randomly according to table of random number： control group, LPS group, sodium hydrosulfide （NaHS） as a donor of H2S＋LPS group and NaHS＋normal saline （NS） group （n=18 in each group）. Rats were challenged with 0.8 ml/kg LPS （200 μg/200 μl） by intratracheal instillation. NaHS （28 μmol/kg, 0.5 ml） was injected intraperitoneally 10 minutes before LPS instillation and 2 hours after LPS instillation. Twelve hours later, 6 rats from each group were sacrificed. Blood from carotid artery was collected to detect H2S content in serum. After that, pulmonary artery rings （PARs） were prepared carefully, then the contraction response of PARs to phenylephrine （PE, 10^-6 mol/L） and the endothelium-dependent relaxation response to acetylcholine （ACh, 10^-6 mol/L） were measured using isolated vascular ring tension detecting technique. Six rats from each group were sacrificed for determination of malondialdehyde （MDA） content of pulmonary artery, and the remaining 6 rats from each group were sacrificed for observation of morphological changes in pulmonary artery tissue. Results Compared with control group, after LPS instillation, the contraction response （g/mg） of PARs to PE increased greatly （0.86±0.20 vs. 0.56±0.13）, the relaxation response to ACh significantly decreased [（65.18±7.05）% vs. （84.13±8.84）%]. MDA content （mmol/L） in pulmonary artery tissues increased （32.03±7.81 vs. 5.82±0.92）, and H2S （μmol/L） content in serum decreased （175.23±27.36 vs. 238.12±16.38）. Changes of all results were significant （P〈0.05 or P〈0.01）. The pulmonary artery tissue and endothelium were injured. However, these changes were reversed by administration of NaHS intraperitoneally, the contraction response of PARs to PE decreased [（0.61±0.17） g/mg

关 键 词：硫化氢 肺动脉 脂多糖 急性肺损伤 肺动脉高压 血管反应性 

分 类 号：R363[医药卫生—病理学]