硫化氢对大鼠内毒素性急性肺损伤的影响

Effect of hydrogen sulfide on acute lung injury induced by lipopolysaccharide in rats

目的观察硫化氢(H2S)对脂多糖(LPS)所致大鼠内毒素性急性肺损伤(ALI)的影响,探讨其对肺脏的作用机制。方法♂SD大鼠共64只,随机分为8组,每组8只:Ⅰ:3h空白对照组;Ⅱ:LPS3h组;Ⅲ:6h空白对照组;Ⅳ:LPS6h组;Ⅴ:LPS+NaHS低剂量组;Ⅵ:LPS+NaHS中剂量组;Ⅶ:LPS+NaHS高剂量组;Ⅷ:LPS+PPG组。LPS3h和LPS6h组给予LPS,其相应空白对照组给予生理盐水,分别在3h或6h时处死大鼠;LPS+NaHS低、中、高剂量组和LPS+PPG组分别在给LPS3h时腹腔注射低、中、高剂量氢硫化钠(NaHS)或炔丙基甘氨酸(PPG),再观察3h后处死大鼠。光、电镜下观察肺组织形态学改变,检测肺系数、肺湿/干重比(W/D)、血浆中H2S含量、肺组织胱硫醚-γ-裂解酶(CSE)活性,以及肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性的变化。结果LPS3h和LPS6h组与相应的空白对照组比较,光、电镜下肺组织明显受损,超微结构明显改变,肺系数、肺湿/干重比和肺组织MDA含量升高,血浆中H2S的含量、肺组织CSE以及SOD、GSH-Px活性降低。LPS+NaHS低、中、高剂量组与LPS6h组比较,光、电镜下肺组织受损情况均有不同程度改善,肺系数、肺湿/干重比和肺组织MDA含量降低,血浆H2S含量、肺组织CSE以及SOD、GSH-Px活性升高。LPS+PPG组与LPS6h组比较,光、电镜下肺组织损伤无改善,肺系数、肺湿/干重比和肺组织MDA含量升高,血浆中H2S的含量、肺组织CSE和SOD活性降低,肺组织GSH-Px活性无明显变化。结论CSE/H2S体系可能参与内毒素性ALI的病理生理过程,外源性补充H2S可减轻内毒素性ALI。

Aim To study the effect of hydrogen sulfide （H2S）on acute lung injury induced by lipopolysaccharide （LPS） in rats. Methods Sixty-four ♂ rats were randomly divided into eight groups （n = 8 ）. Ⅰ control （3 h） group; ⅡLPS 3 h group; Ⅲ control（6 h） group;Ⅳ LPS 6 h group; Ⅴ LPS ＋ Naris low dose group;Ⅵ LPS ＋ NariS middle dose group; Ⅶ LPS ＋ Naris high dose group ; Ⅷ LPS ＋ PPG group. In LPS 3 h and LPS 6h groups, LPS was administrated. Saline was administrated in control groups. The rats were killed at 3 h or 6 h respectively after administration of LPS. In LPS ＋ Naris low, middle, high dose groups or LPS ＋ PPG group, sodium hydrosulfide （NariS） or DLpropargylglycine（PPG） were administrated at 3 h after administration of LPS respectively. The rats were killed at 3 h after administration of Naris or PPG. The morphological changes of lung tissues were observed by light and electron microscopes respectively. The lung coefficient and wet to dry lung tissues weight （W/D） were respectively measured. The content of H2S in plasma and activity of cystathionine-γ-lyase （ CSE ） in lung tissues were respectively detected. The content of malondialdehyde （ MDA ） , and activities of superoxide dismutase （SOD） and glutathione peroxidase （ GSH-Px ） in lung tissues were respectively measured. Results In the LPS 3 h and LPS 6 h groups, the lung tissues were significantly injuried. The lung coefficient, W/D and content of MDA were signifcantly increased com- pared with those of the control group. The content of H2S in plasma,activities of CSE,SOD and GSH-Px in lung tissues were respectively decreased compared with those of the control group. Compared with the LPS 6 h group the injury of the lung tissues was markedly ameliorated, the coefficient ,wet-to-dry weight ratio and content of MDA in lung tissues were respectively decreased and the content of H2S in plasma and activities of CSE, SOD and GSH-Px in lung tissues were significantly increased in the LPS ＋ NariS low, middle and high dose groups. Compared with the LPS 6 h group the in- jury was aggravated, the coefficient, wet-to-dry weight ratio and content of MDA in lung tissues were in- creased,the content of H2S in plasma and activities of CSE and SOD in lung tissues were decreased in the LPS ＋ PPG group, but activity of GSH-Px was not markedly altered. Conclusion The CSE/H2S system might be play a role in the physiopathologic process of the ALI induced by LPS in rats. The administration of NariS could ameliorate the ALI.