一氧化氮在大鼠肝缺血再灌注损伤中的作用

Effect of nitric oxide on liver ischemia/ reperfusion injury in rats in vivo

目的探讨一氧化氮（ｎｉｔｒｉｃｏｘｉｄｅ，ＮＯ）在大鼠肝缺血再灌注（Ｉ／Ｒ）损伤中的作用．方法采用大鼠肝脏原位Ｉ／Ｒ模型，预先经伤寒菌内毒素脂多糖（ＬＰＳ，５００μｇ／ｋｇ）处理，术前腹腔注射Ｌ精氨酸（ＬＡｒｇ，５００ｍｇ／ｋｇ）或Ｌ硝基精氨酸（ＬＮＮＡ，２０ｍｇ／ｋｇ）分别观察分析血清ＮＯ，ＡＬＴ，ＡＳＴ；肝组织ＮＯ、脂质过氧化物（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）以及肝组织病理损伤．结果经ＬＰＳ预处理后引起肝脏ＮＯ的大量合成（ＮＯ，μｍｏｌ／Ｌ，１０８±２１ｖｓ２５±６，Ｐ＜００１，μｍｏｌ／ｇ，０８０９±０１２５ｖｓ０２０８±００７１，Ｐ＜００１）．肝脏经过２０ｍｉｎ缺血和３０ｍｉｎ再灌注后导致明显的肝损伤（ＡＬＴ，ｎｍｏｌ／ｓ，７５５２±７８３ｖｓ１３１７±３６７，Ｐ＜００１，ＡＳＴ，ｎｍｏｌ／ｓ，６５３５±１８６７ｖｓ２４１７±８６７，Ｐ＜００１）．注射ＬＮＮＡ后，抑制了ＮＯ合成，同时更进一步加重了肝损伤（ＡＬＴ，ｎｍｏｌ／ｓ，１９７５４±６３８５ｖｓ７５５２±７８３，Ｐ＜００１，ＡＳＴ，ｎｍｏｌ／ｓ，１９９３７±５９８５ｖｓ６５３５±１８６７，Ｐ＜００１）．而施加Ｌ?

AIM Abstract To investigate the effects of nitric oxide (NO) on hepatic ischemia/ reperfusion ( I/ R ) injury in rats in vivo . METHODS With in situ hepatic I/ R injury model, the rats were pretreated with S.typhimurium lipopolysaccharide (LPS, 500μg/ kg) and then intraperitoneally injected with L arginine (L Arg, 500 mg/ kg ) or N G nitro L arginine (L NNA, 20 mg/ kg ) before operation. NO content, ALT, AST activities in serum, NO and LPO contents and SOD activity in liver tissue as well as hepatic pathology were observed and assayed. RESULTS NO production by rat liver was induced in vivo by pretreatment with LPS (NO, μmol/ L , 108±21 vs 25±6, P <0 01, μmol/ g , 0 809± 0 125 vs 0 208±0 071, P <0 01). Twenty min of ischemia and 30 min of reperfusion led to an increase in hepatic injury (ALT, nmol/ s , 7552±783 vs 1317±367, P <0 01, AST, nmol/ s , 6535±1867 vs 2417±867, P <0 01). Inhibition of NO synthesis with L NNA decreased the LPS induced increase in NO synthesis and markedly increased hepatic injury (ALT, nmol/ s , 19754±6385 vs 7552±783, P <0 01, AST, nmol/ s , 19 937±5985 vs 6535±1867, P <0 01). Elevation of NO (NO, μmol/ L , 266±76 vs 157±49, P <0 01, nmol/ g , 1 195±0 469 vs 0 745±0 261, P <0 05) synthesis with L Arg showed no effects on hepatic injury (ALT, nmol/ s , 5651±1717 vs 7552±783, P >0 05, AST, nmol/ s , 7802±948 vs 6535±1876, P >0 05). SOD activity also decreased in the I/ R and NNA groups (SOD, KNU/ g , 6 8±0 8 vs 8 4±1 3, P <0 05, 6 7±0 9 vs 8 4±1 3, P <0 05), and the effect was ameliorated by the L Arg (SOD, KNU/ g , 8 5±0 6 vs 6 8±0 8, P <0 05). CONCLUSION NO plays a protective role in hepatic I/ R injury in rats during endotoxemia and this effect is mediated by superoxide anion inactivation. Its action seems to be double.