Huang Xin-Li, ma Hui-Jie, Zhou Xiao-Hong, Fan Ya-Min, Xian Xiao-Hui, Cao Hua
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2010 Nov;26(4):477-80.
To study the effects of sodium hydrosulfide (NaHS), hydrogen sulfide (H2S) donor, on LPS-induced polymorphonuclear neutrophil (PMN) accumulation and its mechanism.
The animal model of acute lung injury (ALI) caused by intravenous injection of lipopolysaccharides (LPS). Adult male Spraguce-Dawley (SD) rats were randomly divided into four groups (n = 8 - 12 per group): Control group (0.5 ml/kg normal saline i.v.), LPS-treated group (1 mg/kg, i.v.), LPS plus NaHS (1 mg/kg i.v. and 28 micromol/kg i.p., respectively) and NaHS group (28 micromol/kg i.p.). Animals were sacrificed at 6 h after agent administration. Morphological changes of lung tissues were observed and polymorphonuclear neutrophil (PMN) number in alveolar septum was tested. The apoptosis of PMN in the bronchoalveolar lavage fluid (BALF) was examined with in situ TdT-mediated dUTP end labeling (TUNEL). Intercellular adhesion factor-1 (ICAM-1) and nuclear factor-kappaB (NF-kappaB) expressions in the lung tissue were analyzed by Western Blot.
The results showed that bleeding, edema, PMN accumulation and other pathological signs in the lung tissue emerged after LPS injection. Compared to control rats, the LPS-treated rats had increased PMN number, decreased PMN apoptotic percentages, and increased expressions of ICAM-1 and NF-kappaB. Administration of NaHS into LPS-treated rats reduced the PMN number and expressions of ICAM-1 and NF-kappaB but increased PMN apoptotic percentages. In addition, NaHS alleviated the degree of ALI. There were no significant differences of the above indicators between NaHS-treated rats and control rats.
NaHS can reduce the PMN accumulation in the lung, and its mechanism is related to down-regulation expression of ICAM-1 and promotion of PMN apoptosis induced by inhibition of NF-kappaB pathway.
研究硫化氢供体硫氢化钠（NaHS）对脂多糖（LPS）诱导的多形核中性粒细胞（PMN）聚集的影响及其机制。
采用静脉注射脂多糖（LPS）建立急性肺损伤（ALI）动物模型。成年雄性Spraguce-Dawley（SD）大鼠随机分为四组（每组n = 8 - 12）：对照组（静脉注射0.5 ml/kg生理盐水）、LPS处理组（静脉注射1 mg/kg）、LPS + NaHS组（分别静脉注射1 mg/kg和腹腔注射28 μmol/kg）和NaHS组（腹腔注射28 μmol/kg）。给药后6小时处死动物。观察肺组织形态学变化，检测肺泡隔中多形核中性粒细胞（PMN）数量。采用原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测支气管肺泡灌洗液（BALF）中PMN的凋亡情况。通过蛋白质免疫印迹法分析肺组织中细胞间黏附分子-1（ICAM-1）和核因子-κB（NF-κB）的表达。
结果显示，注射LPS后肺组织出现出血、水肿、PMN聚集等病理征象。与对照大鼠相比，LPS处理组大鼠PMN数量增加，PMN凋亡百分比降低，ICAM-1和NF-κB表达增加。给LPS处理的大鼠注射NaHS可减少PMN数量以及ICAM-1和NF-κB的表达，但增加PMN凋亡百分比。此外，NaHS减轻了ALI的程度。NaHS处理组大鼠与对照组大鼠上述指标无显著差异。
NaHS可减少肺内PMN聚集，其机制与下调ICAM-1表达以及通过抑制NF-κB途径促进PMN凋亡有关。
