N-单甲基左旋精氨酸对脾切除后大鼠内毒素休克的治疗作用

An Experimental Study on The Effects of NGmonomethylLarginine (LNMMA) in an Endotoxic Shock Model of Postsplenectomy in Rats

通过观察脾切除术后大鼠内毒素休克时血压及血浆一氧化氮（ＮＯ）代谢产物的变化，以评价ＮＯ在无脾动物凶险性感染发病中作用及一氧化氮合成酶（ＮＯＳ）抑制剂Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭ－ＭＡ）的治疗效果。Ｗｉｓｔａｒ大鼠脾切除或假手术术后两周，静脉注射内毒素，动态监测血压及血浆亚硝酸盐／硝酸盐浓度，并记录动物死亡率。结果显示：内毒素攻击后大鼠平均动脉压有不同程度下降，ＮＯ水平明显升高，其中无脾动物血压呈进行性降低，程度更重，持续时间更长，血浆ＮＯ代谢产物亚硝酸盐升高更著；应用Ｌ－ＮＭＭＡ后，血压明显回升，死亡率降低。提示：无脾动物对内毒素更敏感，左旋精氨酸：一氧化氮（Ｌ－ａｒｇ：ＮＯ）通路活性在无脾动物明显增高，这可能与革兰氏阴性细菌诱发的脾切除术后凶险性感染（ＯＰＳＩ）发生有关。Ｌ－ＮＭＭＡ对稳定ＯＰＳＩ早期循环状态。

The aim of this experiment is to study the therapeutic effects of NGmonomethylLarginine (LNMMA), a potent inhibitor of nitric oxide synthase, on the endotoxic shock rats of postsplenectomy. Wistar rats were insulted with E coli Lipopolysaccride (LPS 10mg/kg iv. bolus) two weeks after splenectomy or sham operation (Control group); One group of asplenic rats were treated with LNMMA. Serial changes of arterial blood pressure and the plasma nitrite and nitrate were measured and the survival of the animals were recorded. The results showed that LPS caused a rapid (within 5 min) and sustained fall in mean arterial pressure (MAP), while the plasma nitrite and nitrate increased significantly. The MAP in asplenic rats were much lower than that in control group (P<0.01), and its hypotension lasted longer. The mortality rate in asplenic rats were much higher than that in control group. Administration of LNMMA significantly attenuated the fall in MAP and diminished the increase in plasma nitrite and nitrate (P<0.01 or 0.05), and reduced the mortality. The results indicated that asplenic rats were more sensitive to endotoxin. The activity of nitric oxide synthase in aspleen rats increased significantly. This may be responsible for the onset of overwhelming postsplenectomy infection (OPSI) caused by gram negative bacteria. The inhibiation of nitric oxide synthase might be helpful in the treatment of OPSI.