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ω-3 衍生物,专门的促解决介质:治疗慢性肝病疼痛的有前途的治疗工具。

Omega-3 derivatives, specialized pro-resolving mediators: Promising therapeutic tools for the treatment of pain in chronic liver disease.

机构信息

Centro de Investigaciones Medicas, Escuela de Medicina, Universidad de Talca, Talca, Chile.

Centro de Investigaciones Medicas, Escuela de Medicina, Universidad de Talca, Talca, Chile.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2020 Jul;158:102095. doi: 10.1016/j.plefa.2020.102095. Epub 2020 May 17.

DOI:10.1016/j.plefa.2020.102095
PMID:32450460
Abstract

The main causes of liver injury are associated with inflammation and permanent damage. They can cause chronic liver disease (CLD), which is mainly related to viral hepatitis, alcohol consumption and non-alcoholic steatohepatitis, leading to fibrosis, cirrhosis and hepatocellular carcinoma. These conditions prevent the liver from working normally and make it begin to fail, which in turn may prompt a liver transplant. CLD and cirrhosis are the eleventh cause of death worldwide. At present, there are no approved pharmacological treatments to prevent, treat or resolve liver fibrosis. The prevalence of pain in the hepatic disease is elevated with ranges between 30% and 40%. Most of the pain drugs require hepatic function; therefore, the suitable control of pain is still a clinical challenge. Specialized pro-resolving mediators (SPM): lipoxins, resolvins, protectins and maresins, are potent endogenous molecules (nM concentrations) that modulate inflammatory body responses by reducing neutrophil infiltration, macrophage activity and pain sensitization. SPM have anti-inflammatory properties, stimulate tissue resolution, repair and regeneration, and exhibit anti-nociceptive actions. Furthermore, SPM were tried on different cellular, animal models and human observational data of liver injury, improving the pathogenesis of inflammation and fibrosis. In the present work, we will describe recent evidence that suggests that SPM can be used as a therapeutic option for CLD. Additionally, we will examine the role of SPM in the control of pain in pathologies associated with liver injury.

摘要

肝脏损伤的主要原因与炎症和永久性损伤有关。这些原因可能导致慢性肝病(CLD),主要与病毒性肝炎、酒精摄入和非酒精性脂肪性肝炎有关,导致纤维化、肝硬化和肝细胞癌。这些情况会阻止肝脏正常工作,并使其开始衰竭,这可能会促使进行肝移植。CLD 和肝硬化是全球第十一位死亡原因。目前,尚无批准的药物治疗方法可预防、治疗或解决肝纤维化。肝病疼痛的发生率较高,范围在 30%至 40%之间。大多数止痛药物都需要肝功能;因此,疼痛的适当控制仍然是一个临床挑战。特殊的促解决介质(SPM):脂氧素、解析素、保护素和maresin,是强效的内源性分子(nM 浓度),通过减少中性粒细胞浸润、巨噬细胞活性和疼痛敏化来调节全身炎症反应。SPM 具有抗炎特性,可刺激组织修复、再生,并具有抗伤害感受作用。此外,SPM 已在不同的细胞、动物模型和人类肝损伤观察数据中进行了尝试,改善了炎症和纤维化的发病机制。在本工作中,我们将描述最近的证据表明 SPM 可作为 CLD 的治疗选择。此外,我们将研究 SPM 在控制与肝损伤相关的病理疼痛中的作用。

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