N-乙酰半胱氨酸对梗阻性黄疸大鼠肠黏膜屏障的保护作用

目的:研究N-乙酰半胱氨酸(NAC)对梗阻性黄疸大鼠肠黏膜屏障的保护作用。方法:30只雄性Wistar大鼠随机平均分为3组:假手术组(SO),胆总管结扎组(BDL),胆总管结扎+N-乙酰半胱氨酸组(BDL+NAC)即治疗组。BDL+NAC组大鼠胆总管结扎术后第1天开始,每天腹腔给予NAC(150 mg/kg,腹腔注射,每天1次),而SO、BDL组大鼠每只每天腹腔给予同等剂量生理盐水。在术后第7天检测血浆总胆红素(TBIL)和门静脉血的内毒素水平;比色法测定回肠末端肠道组织匀浆的髓过氧化物酶(MPO)的活性水平;光镜下观察肠道的黏膜厚度和绒毛密度;免疫组化法测定末端回肠组织基质金属蛋白酶-9(MMP-9)的表达水平。结果:BDL组大鼠较SO组血浆TBIL和门静脉血内毒素水平明显升高(P<0.05);肠道黏膜厚度和绒毛密度降低(P<0.05);末端回肠组织MPO活性水平升高(P<0.05);同时末端回肠组织MMP-9表达水平升高(P<0.05)。与BDL组大鼠相比,BDL+NAC组大鼠门静脉血内毒素水平明显降低(P<0.05);肠道黏膜厚度和绒毛密度增加(P<0.05);末端回肠组织MPO活性水平降低(P<0.05);同时末端回肠组织MMP-9表达水平降低(P<0.05)。结论:NAC能够有效减轻肠道黏膜的损伤,改善梗阻性黄疸大鼠肠道屏障功能,降低门静脉内毒素水平。

Protective Effect of N-Acetylcysteine on Intestinal Barrier in Obstructive Jaundice of Rats

Objective: To study the protective effect of N-acetylcysteine(NAC) on intestine in obstructive jaundice rats.Methods: Thirty male Wistar rats were randomly and equally divided into three groups as sham operation(SO),bile duct ligation(BDL),and BDL+NAC group(150 mg/kg per day NAC intraperitoneal injection after BDL).On the 7th day,levels of serum total bilirubin and endotoxin level in portal vein blood were measured,myeloperoxidase and MMP-9 of terminal ileum homogenates were determined,and the mucosal thickness and villus density of terminal ileum were examined.Results: Levels of serum total bilirubin and endotoxin in portal vein of rats in BDL group significantly increased;myeloperoxidase level increased,mucosal thickness and villus density of terminal ileum decreased,and MMP-9 expression increased(all P<0.05).Compared with those in BDL group,level of endotoxin in portal vein significantly decreased(P<0.05);myeloperoxidase decreased,mucosal thickness and villus density of terminal ileum increased,and MMP-9 expression decreased in BDL + NAC group(all P<0.05).Conclusion: NAC can decrease the level of intestinal oxidative stress and endotoxemia of portal vein in bile duct ligated rats,and alleviate intestinal mucosal injury.