Li Meng, Li Tian-shui, Liu Zhi-wei, Guan Lan, Jin Hong-fang, Zhao Bin, DU Jun-bao
Department of Emergency Medicine, Beijing Jishuitan Hospital, Beijing, China.
Zhonghua Yi Xue Za Zhi. 2011 Nov 22;91(43):3054-7.
To explore the potential effects of hydrogen sulfide (H(2)S) on nuclear factor kappa B (NF-κB) and intercellular adhesion molecule 1 (ICAM-1) in lung tissue with oleic acid (OA)-induced acute lung injury (ALI) in rats.
Forty-two rats were randomly divided into 3 groups: control (n = 6), OA (n = 18) and OA + NaHS (n = 18). Rats in the OA group received an intra-tail vein injection of oleic acid 0.1 ml/kg while those in the OA + NaHS group an intraperitoneal injection of NaHS 56 µmol/kg at 30 mins before OA injection. The OA and OA + NaHS groups were subdivided into 3 subgroups depending on the therapeutic duration: 2 h (n = 6), 4 h (n = 6) and 6 h (n = 6). Rats in the control group received an intra-tail vein injection of normal saline 0.1 ml/kg. Bronchioalveolar lavage fluid (BALF) was collected and the leucocytic differential count of sediment examined. The extent of lung injury was evaluated by the index of quantitative assessment (IQA). The H(2)S level in lung tissue was measured by sensitive sulphur electrode. The nuclear translocation of NF-κB and the expression of ICAM-1 in alveolar epithelial cells were measured by immunohistochemical staining.
Compared with the control group, the BALF percentage of polymorphonuclear (PMN) cell was significantly higher at 2, 4 and 6 h in the OA-treated rats [(74.5 ± 3.0)%, (80.2 ± 2.0)%, (87.2 ± 2.7)% vs (3.1 ± 1.6)%, all P < 0.01]. And the value of IQA increased significantly versus those at 2, 4 and 6 h in the control group (5.2 ± 0.8, 6.4 ± 0.6, 6.8 ± 0.8 vs 0.4 ± 0.6, all P < 0.01). And the levels of H(2)S in lung tissue decreased at 2, 4 and 6 h [(21.20 ± 0.38) µmol/g, (20.80 ± 0.53) µmol/g, (18.92 ± 0.75) µmol/g vs (26.81 ± 0.65) µmol/g, all P < 0.01]. Moreover, the nuclear expression of NF-κB and the membranous expression of ICAM-1 in the alveolar epithelial cells in OA group rats was significantly higher than those of the control group (all P < 0.05). After the dosing of H(2)S donor (NaHS), the BALF percentage of PMN cell and the lung IQA decreased in the three subgroup rats (2, 4 and 6 h) versus the OA group. And the concentration of H(2)S increased significantly in the 4 h and 6 h subgroups versus the OA group at the corresponding time points. Simultaneously, the nuclear expression of NF-κB and the membranous expression of ICAM-1 in alveolar epithelial cells were significantly lower than that of the OA group at 4 h and 6 h subgroups (all P < 0.05).
H(2)S may play a protective role in the ALI rats through the suppression of lung inflammation. And the inhibited expression of alveolar epithelial cell NF-κB mediates the anti-inflammatory effects of H(2)S.
探讨硫化氢(H₂S)对油酸(OA)诱导的大鼠急性肺损伤(ALI)肺组织中核因子κB(NF-κB)和细胞间黏附分子1(ICAM-1)的潜在影响。
42只大鼠随机分为3组:对照组(n = 6)、OA组(n = 18)和OA + NaHS组(n = 18)。OA组大鼠经尾静脉注射0.1 ml/kg油酸,而OA + NaHS组大鼠在注射OA前30分钟腹腔注射56 μmol/kg NaHS。根据治疗持续时间,OA组和OA + NaHS组再分为3个亚组:2小时(n = 6)、4小时(n = 6)和6小时(n = 6)。对照组大鼠经尾静脉注射0.1 ml/kg生理盐水。收集支气管肺泡灌洗液(BALF)并检查沉淀物的白细胞分类计数。通过定量评估指数(IQA)评估肺损伤程度。用灵敏硫电极测量肺组织中的H₂S水平。通过免疫组织化学染色测量肺泡上皮细胞中NF-κB的核转位和ICAM-1的表达。
与对照组相比,OA处理的大鼠在2、4和6小时时BALF中多形核(PMN)细胞百分比显著更高[(74.5 ± 3.0)%,(80.2 ± 2.0)%,(87.2 ± 2.7)%对(3.1 ± 1.6)%,所有P < 0.01]。并且IQA值与对照组在2、4和6小时时相比显著增加(5.2 ± 0.8,6.4 ± 0.6,6.8 ± 0.8对0.4 ± 0.6,所有P < 0.01)。并且肺组织中H₂S水平在2、4和6小时时降低[(21.20 ± 0.38)μmol/g,(20.80 ± 0.53)μmol/g,(18.92 ± 0.75)μmol/g对(26.81 ± 0.65)μmol/g,所有P < 0.01]。此外,OA组大鼠肺泡上皮细胞中NF-κB的核表达和ICAM-1的膜表达显著高于对照组(所有P < 0.05)。给予H₂S供体(NaHS)后,三个亚组大鼠(2、4和6小时)的BALF中PMN细胞百分比和肺IQA均低于OA组。并且在相应时间点,4小时和6小时亚组的H₂S浓度相对于OA组显著增加。同时,在4小时和6小时亚组中,肺泡上皮细胞中NF-κB的核表达和ICAM-1的膜表达显著低于OA组(所有P < 0.05)。
H₂S可能通过抑制肺部炎症在ALI大鼠中发挥保护作用。并且肺泡上皮细胞NF-κB表达的抑制介导了H₂S的抗炎作用。