Mishima S, Xu D, Lu Q, Deitch E A
Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103-2714, USA.
J Trauma. 1998 Jan;44(1):175-82. doi: 10.1097/00005373-199801000-00025.
This study examines the hypothesis that there is a relationship among endotoxin-induced bacterial translocation (BT) and increased nitric oxide (NO) production and that inhibition of excessive NO production with NG-monomethyl-L-arginine (L-NMMA) is beneficial.
Rats received 0, 1, or 4 mg/kg endotoxin intraperitoneally, and 6 or 18 hours later, they were killed and BT, NO production (as reflected in nitrite/nitrate levels), and calcium-dependent nitric oxide synthase and calcium-independent nitric oxide synthase (iNOS) activities were measured in tissues (ileum, liver, and mesenteric lymph nodes) and blood. In a second set of experiments, the animals received the NOS inhibitor L-NMMA (100 mg/kg) intravenously either 15 minutes before or 2 hours after endotoxin challenge (4 mg/kg) and the same parameters were measured.
The incidence of BT was higher in rats receiving 4 mg/kg endotoxin (62.5%) than in the control group (0%, p < 0.05), and the 1 mg/kg endotoxin group had intermediate incidence (25%). The animals receiving 4 mg/kg endotoxin had higher tissue (mesenteric lymph nodes, liver) and blood nitrite/nitrate levels than the control or 1 mg/kg endotoxin groups. The increased NO production was mainly attributable to an elevated level of iNOS activity. The administration of L-NMMA before but not after endotoxin challenge reduced iNOS activity, NO production, and BT to control levels at 6 hours but not 18 hours after endotoxin administration.
Endotoxin-induced mucosal injury and BT are associated with iNOS activity and increased NO production. Inhibition of iNOS activity with L-NMMA before treatment prevented endotoxin-induced ileal mucosal injury and BT.
本研究检验了以下假设，即内毒素诱导的细菌移位（BT）与一氧化氮（NO）生成增加之间存在关联，并且用N-甲基-L-精氨酸（L-NMMA）抑制过量的NO生成是有益的。
大鼠腹腔注射0、1或4mg/kg内毒素，6或18小时后处死，测量组织（回肠、肝脏和肠系膜淋巴结）和血液中的BT、NO生成（以亚硝酸盐/硝酸盐水平反映）以及钙依赖性一氧化氮合酶和钙非依赖性一氧化氮合酶（iNOS）活性。在第二组实验中，动物在接受内毒素攻击（4mg/kg）前15分钟或后2小时静脉注射NOS抑制剂L-NMMA（100mg/kg），并测量相同参数。
接受4mg/kg内毒素的大鼠中BT的发生率（62.5%）高于对照组（0%，p<0.05），1mg/kg内毒素组的发生率处于中间水平（25%）。接受4mg/kg内毒素的动物组织（肠系膜淋巴结、肝脏）和血液中的亚硝酸盐/硝酸盐水平高于对照组或1mg/kg内毒素组。NO生成增加主要归因于iNOS活性水平升高。在内毒素攻击前而非攻击后给予L-NMMA可将iNOS活性、NO生成和BT在给予内毒素后6小时而非18小时降至对照水平。
内毒素诱导的黏膜损伤和BT与iNOS活性及NO生成增加有关。治疗前用L-NMMA抑制iNOS活性可预防内毒素诱导的回肠黏膜损伤和BT。
