硫化氢对大鼠内毒性急性肺损伤炎性反应及单免疫球蛋白白介素-1相关蛋白表达的影响

Effects of Hhydrogen Sulfide on the Inflammatory Reaction and the Expression of Single Immunoglobin IL-1 Receptor Related Protein in Rats with Acute Lung Injury Induced by Lipopolysaccharide

目的探讨吸入硫化氢(hydrogen sulfide,H_2S)对脂多糖(lipopolysaccharide,LPS)诱导人肺泡上皮A549细胞炎性反应及单免疫球蛋白白介素-1受体相关蛋白(single immunoglobin IL-1 receptor related protein,SIGIRR)表达的影响。方法雄性SD大鼠40只分4组,每组10只。正常小鼠组;H_2S吸入组:仅吸入H_2S 80mg/m36h;ALI模型组:腹腔注射15mg/kg LPS;ALI+H_2S吸入组:腹腔注射15mg/kg LPS 1h后即吸入H_2S 80mg/m^3 6h,实验结束处死大鼠,观察肺组织病理学改变;ELISA法测肺组织匀浆及血浆中TNF-α及IL-1β水平;Western blot法检测肺组织SIGIRR蛋白表达水平。结果与正常大鼠及吸入H_2S组比较,ALI模型组大鼠出现典型急性肺损伤病理改变,肺损伤评分升高(P<0.05),肺组织匀浆及血浆中TNF-α及IL-1β水平增加(P<0.05);而给予吸入H_2S后,可减轻大鼠肺损伤程度(P<0.05),肺组织匀浆及血浆中TNF-α及IL-1β水平下降(P<0.05),且与ALI模型组相比,给予吸入H_2S后可上调肺损伤大鼠肺组织内SIGIRR的表达。结论吸入H_2S对内毒素性急性肺损伤大鼠具有保护作用,抑制肺组织匀浆及血浆中炎性因子产生,促进负调控分子SIGIRR表达是可能的分子机制。

Objective To explore the effects of hydrogen sulfide （H2S） on the inflammatory reaction and the expression of single immunoglobin IL - 1 receptor related protein （SIGIRR） in rats with acute lung injury （ALI） induced by lipopolysaeeharide （LPS）. Methods Forty male SD rats were randomly divided into 4 groups （normal group, H2S group, ALl group and ALI ＋ H2S group）. The ALl rat model was established by LPS peritoneal injection. After LPS stimulation for 1 h, rats inhaled H2S 80mg/m3 for 6h. Then, rats were sacrificed with a supraphysiological dose of pentobarbital sodium. The histological changes in the lung, the levels of TNF-α and IL - 1β in serum and lung tissue homogenates, and the protein expression of SIGIRR in lung tissues were examined. Results Compared with the normal and H2S groups, typical histological features of ALI were observed in ALI group, and the lung injury scores of ALI group were higher than those of the normal and H2S groups （P 〈 0.05 ）. Moreover, there were marked increases in the levels of TNF - α and IL - 1β in serum and lung tissue homogenates after LPS injection. In contrast, inhalation of H：S could attenuate lung pathological changes and inhibit the productions of TNF -α and IL - 1β in serum and lung tissue homogenates （ P 〈 0.05 ）. Additionally, inhalation of H2S could induce the protein expression of SIGIRR in rat lung tissues. Conclusion Inhalation of H2S protected rats from LPS - induced ALI and its mechanisms were partially associated with inhibition of the productions of TNF - α and IL - 1β and modulation of SIGIRR expres- sioN.