基于环氧合酶-2通路探讨葛花解酲汤治疗慢性酒精中毒的作用机制  

Gehua Jiecheng Decoction Treats Chronic Alcoholism via COX-2 Pathway

作　　者：王夕丹 周悦 路旭 孙良颖 王林江 尹瑶 张月华 WANG Xidan;ZHOU Yue;LU Xu;SUN Liangying;WANG Linjiang;YIN Yao;ZHANG Yuehua(The People's Hospital of Liupanshui City,Liupanshui 553000,China)

机构地区：[1]贵州省六盘水市人民医院,六盘水553000

出　　处：《世界中医药》2022年第11期1584-1589,共6页World Chinese Medicine

基　　金：贵州省中医药管理局资助项目(QZYY2015023)。

摘　　要：目的:观察基于环氧合酶-2(COX-2)通路葛花解酲汤治疗慢性酒精中毒的作用机制。方法:将60只C57BL/6J小鼠随机分为5组,分别为正常组、模型组、低剂量葛花解酲汤组、中剂量葛花解酲汤组和高剂量葛花解酲汤组,对其建模处理,通过组织学检查、Western Blotting检测、化学比色法测定等对小鼠组织中COX-2蛋白、脑组织δ阿片受体(DOR)mRNA、β-内啡肽、胱硫醚-β-合酶(CBS)活性和H_(2)S水平,肝组织乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)活性和抗氧化指标进行对比。结果:低剂量葛花解酲汤组中COX-2蛋白水平显著低于模型组(P<0.05),高剂量葛花解酲汤组COX-2蛋白水平显著低于中剂量葛花解汤组(P<0.05);低剂量葛花解酲汤组中DOR mRNA和β-内啡肽的水平显著低酲于模型组(P<0.05);高剂量葛花解酲汤组DOR mRNA和β-内啡肽的水平显著低于中剂量葛花解酲汤组(P<0.05);低剂量葛花解酲汤组中CBS活性和H_(2)S水平显著低于模型组(P<0.05),高剂量葛花解酲汤组CBS活性和H_(2)S水平显著低于中剂量葛花解酲汤组(P<0.05),低剂量葛花解酲汤组中的ADH和ALDH活性较模型组比较显著升高(P<0.05),高剂量葛花解酲汤组的ADH活性与中剂量葛花解酲汤组相比明显降低(P<0.05);低剂量葛花解酲汤组中谷胱甘肽(GSH)、谷胱甘肽转硫酶(GST)和总抗氧化能力(T-AOC)水平明显高于模型组(P<0.05),高剂量葛花解酲汤组GSH、GST和T-AOC水平显著高于中剂量葛花解酲汤组(P<0.05)。结论:葛花解酲汤可以有效抑制COX-2通路,降低慢性酒精中毒小鼠脑组织中DOR mRNA、β-内啡肽、CBS活性和H_(2)S水平,显著提高慢性酒精中毒小鼠肝脏中的ADH和ALDH的活性,改善氧化应激指标。Objective:To decipher the mechanism of Gehua Jiecheng Decoction in the treatment of chronic alcoholism via COX-2 pathway.Methods:Sixty C57BL/6J mice were randomly assigned into five groups:a normal group,a model group,and low-,medium-,and high-dose Gehua Jiecheng Decoction groups.The COX-2 protein level,delta-opioid receptor(DOR)mRNA level,β-endorphin,cystathionine-beta-synthase(CBS)activity,and H_(2)S level were determined by histological examination,Western blotting,and chemical colorimetry.The alcohol dehydrogenase(ADH)and acetaldehyde dehydrogenase(ALDH)activities and the antioxidant indexes including glutathione(GSH),glutathione S-transferase(GST),and total antioxidant capacity(T-AOC)in the liver tissue were compared between groups.Results:The COX-2 protein level,DOR mRNA level,β-endorphin level,CBS activity,and H_(2)S level were lower in the low-dose Gehua Jiecheng Decoction group than in the model group(P<0.05)and lower in the high-dose Gehua Jiecheng Decoction group than in the medium-dose Gehua Jiecheng Decoction group(P<0.05).The activities of ADH and ALDH were higher in the low-dose Gehua Jiecheng Decoction group than in the model group(P<0.05),and the ADH activity in the high-dose Gehua Jiecheng Decoction group was lower than that in the medium-dose Gehua Jiejiu Decoction group(P<0.05).The GSH,GST,and T-AOC levels were higher in the low-dose Gehua Jiecheng Decoction group than in the model group(P<0.05)and higher in the high-dose Gehua Jiecheng Decoction group than in the medium-dose Gehua Jiecheng Decoction group(P<0.05).Conclusion:Gehua Jiecheng Decoction can inhibit COX-2 pathway,decrease DOR mRNA level,β-endorphin level,CBS activity,and H_(2)S level in brain tissue,increase the activities of ADH and ALDH in the liver tissue,and alleviate the oxidative stress in the mice with chronic alcoholism.

关 键 词：环氧合酶-2通路 葛花解酲汤 慢性酒精中毒 δ阿片受体mRNA Β-内啡肽 胱硫醚-β-合酶活性 

分 类 号：R289.5[医药卫生—方剂学]