Chen Jiaying, Wu Feixiang, Long Yue, Yu Weifeng
Department of Anesthesia & Intensive Care, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200438, China ; Department of Anesthesiology, 81st Hospital of the Chinese PLA, Nanjing 210002, China.
Department of Anesthesia & Intensive Care, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200438, China.
Oxid Med Cell Longev. 2015;2015:486148. doi: 10.1155/2015/486148. Epub 2015 Jun 16.
We investigated the protective effects and mechanism of glutathione (GSH) on vascular hyporesponsiveness induced by bile duct ligation (BDL) in a rat model. Seventy-two male Sprague-Dawley rats were randomly divided into four groups: a NS group, a GSH group, a BDL + NS group, and a BDL + GSH group. GSH was administrated into rats in the GSH and BDL + GSH groups by gastric gavage. An equal volume of normal saline was, respectively, given in the NS group and BDL + NS group. Blood was gathered for serological determination and thoracic aorta rings were isolated for measurement of isometric tension. Obstructive jaundice led to a significant increase in the serum total bilirubin, AST, and ALT levels. The proinflammatory cytokines levels (TNF-α and IL-1β), concentration of NO, and oxidative stress markers (MDA and 3-NT) were increased as well. All of those were reduced by the treatment of GSH. Meanwhile, contraction of aorta rings to NA and vasorelaxation to ACh or SNP in the BDL group rats were markedly decreased, while GSH administration reversed this change. Our findings suggested that GSH supplementation attenuated overexpressed ONOO(-) from the reaction of excessive NO with O2 (∙-) and protected against obstructive jaundice-induced vascular hyporesponsiveness in rats.
我们在大鼠模型中研究了谷胱甘肽（GSH）对胆管结扎（BDL）诱导的血管反应性降低的保护作用及其机制。将72只雄性Sprague-Dawley大鼠随机分为四组：生理盐水组（NS组）、GSH组、BDL + NS组和BDL + GSH组。通过胃管向GSH组和BDL + GSH组的大鼠给予GSH。NS组和BDL + NS组分别给予等体积的生理盐水。采集血液进行血清学测定，并分离胸主动脉环以测量等长张力。梗阻性黄疸导致血清总胆红素、AST和ALT水平显著升高。促炎细胞因子水平（TNF-α和IL-1β）、NO浓度以及氧化应激标志物（MDA和3-NT）也升高。GSH治疗可降低所有这些指标。同时，BDL组大鼠主动脉环对去甲肾上腺素（NA）的收缩反应以及对乙酰胆碱（ACh）或硝普钠（SNP）的血管舒张反应明显降低，而给予GSH可逆转这种变化。我们的研究结果表明，补充GSH可减弱过量NO与超氧阴离子（O2(∙-)）反应产生的过表达的过氧亚硝酸盐（ONOO(-)），并预防大鼠梗阻性黄疸诱导的血管反应性降低。
