Ghiassy Bentolhoda, Rahimi Nastaran, Javadi-Paydar Mehrak, Gharedaghi Mohammad Hadi, Norouzi-Javidan Abbas, Dehpour Ahmad R
a Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
b Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
Can J Physiol Pharmacol. 2017 Jan;95(1):16-22. doi: 10.1139/cjpp-2016-0188. Epub 2016 Aug 7.
Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NO concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.
近期研究表明，内源性阿片类物质和一氧化氮（NO）参与了肝性脑病（HE）的病理生理过程。在本研究中，我们探讨了阿片受体拮抗剂与NO在脂多糖（LPS）诱导的肝硬化大鼠肝性脑病中的相互作用。将雄性大鼠分为假手术组和胆管结扎（BDL）手术组。动物分别接受生理盐水、纳曲酮（10 mg/kg，腹腔注射）、L- NAME（3 mg/kg，腹腔注射）单独或与纳曲酮联合治疗。在最后一次药物治疗1小时后，腹腔注射LPS（1 mg/kg）以诱导肝性脑病。记录肝性脑病评分、肝脏组织学、血浆NO代谢产物水平及死亡率。肝硬化大鼠经纳曲酮急性和慢性治疗后，LPS给药后意识水平恶化和死亡率显著改善。然而，L- NAME的急性和慢性给药并未改变肝硬化大鼠的肝性脑病评分。L- NAME可逆转纳曲酮急性而非慢性治疗对肝性脑病参数的影响。BDL大鼠血浆NO浓度升高，经纳曲酮或L- NAME急性和慢性治疗后显著降低。我们认为，纳曲酮的急性和慢性治疗均可改善LPS诱导的肝性脑病。但是，只有纳曲酮的急性治疗可能通过NO途径起作用。
