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内、外源性硫化氢在脂多糖所致大鼠急性肺损伤中的作用
  • 期刊名称:中国应用生理学杂志
  • 时间:0
  • 页码:289-294
  • 语言:中文
  • 分类:R363[医药卫生—病理学;医药卫生—基础医学]
  • 作者机构:[1]河北医科大学病理生理学教研室,河北石家庄050091
  • 相关基金:国家自然科学基金项目(30800440);河北省教育厅自然科学指令项目(2007476);河北省自然科学基金项目(C2008001040;C2007000830);河北省卫生厅医学重点指令项目(08058)
  • 相关项目:CSE/H2S在内毒素急性肺损伤发生中的作用及其机制研究
中文摘要:

目的:探讨内、外源性硫化氢(H2S)在脂多糖(LPS)所致大鼠急性肺损伤(ALI)中的作用并初探其机制。方法:将120只SD大鼠随机分为对照组、IPS组(经气管内滴注LPS复制ALI模型)、NaHS+LPS组和炔丙基甘氨酸(PPG)+LPS组。给药后4h或8h处死动物,测定肺系数;光镜观察肺组织形态学改变;化学法检测血浆H2S、NO和CO含量、肺组织丙二醛(MDA)含量、胱硫醚-γ-裂解酶(CSE)、诱导型一氧化氮合酶(iNOS)和血红素加氧酶(HO)活性以及支气管肺泡灌洗液(BALF)中中性粒细胞(PMN)数目和蛋白含量的变化;用免疫组织化学法检测肺组织iNOS、HO-1蛋白表达。再将血浆H2S含量与上述指标进行相关性分析。结果:气管内滴注LPS可引起肺组织明显的形态学改变;肺系数和肺组织MDA含量增加;BALF中PMN数目和蛋白含量增加;血浆H2S含量和肺组织CSE活性下降;肺组织iNOS活性、HO活性和iNOS蛋白表达、HO-1蛋白表达增强,血浆NO含量、CO含量增加。预先给予NaHS可显著减轻LPS所致上述指标的改变;而预先给予PIG可加重LPS所致肺损伤,使BALF中PMN数目和蛋白含量、血浆NO含量、肺组织iNOS活性和iNOS蛋白表达进一步增加,但对血浆CO含量、肺组织HO活性和HO-1蛋白表达无明显影响。HS含量与CSE活性、血浆CO含量、肺组织HO-1活性呈正相关(r值=0.945—0.987,P均〈0.01);与其他指标呈负相关(r值=-0.994~-0.943,P均〈0.01)。结论:H2S/CSE体系的下调在LPS所致大鼠Ⅲ的发病学中有一定作用,内、外源性H2S具有抗LPS所致Au的作用,该作用可能与其抗氧化效应、减轻PMN所致肺过度的炎症反应以及下调NO/iNOS体系、上调CO/HO—1体系有一定关系。

英文摘要:

Aim: To explore the role of endogenous and exogenous hydrogen sulfide(H2S) in lipopolysaccharide(LPS)-induced acute lung injury (ALI) in rats and the underlying mechanisms. Methods: 120 Sprague-Dawley rats were randomly divided into four groups: control, LPS(instilled intratracheally to induce ALI), NaHS(H:S donor) + LPS, and propargylglycin(PPG) + LPS. Animals were sacrificed at 4 h or 8 h after agent administration. Lung weight/body weight ratio(LW/BW) was measured and calculated. Morphological changes of lung tissues were observed. H2S concentration, NO concentration(NO) and carbon monoxide(CO) level in plasma were tested. Malondialdehyde(MDA) content, CSE activity, inducible nitric oxide synthase(iNOS) activity and hemeoxygenase(HO) activity of the lung were determined. PMN and protein content in BALF were also tested. Immunohistochemisty technique was performed to examine the expression of iNOS and HO-1 protein in lung tissues. The correlation of H2S content with the above indices was analyzed. Results: Compared with control conditions, severe injuries of lung tissues and a raised LW/BW, MDA content, PMN and protein content in BALF were observed in rats treated with LPS. LPS also lead to a drop in plasma H2S concentration and lung CSE activity. The enzyme activity of iNOS and HO, the protein expression of them and plasma NO, CO level increased after LPS instillation. Administration of NailS before LPS could attenuated the changes induced by LPS. Pre-administration of PPG exacerbated the injuries induced by LPS, increased PMN and protein content in BALF, the plasma NO level, lung iNOS activity and its protein expression, but there was no prominent variation in CO level, HO activity and HO-1 protein expression compared with those of LPS group. The H2S content was positively correlated with CSE activity, CO content and HO- 1 activity( r = 0. 945 - 0. 987, P 〈 0. 01 ), and negatively correlated with the other indices( r = -0.994 - -0.943, P ?

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