Ramalho F N, Sanches S C, Foss M C, Augusto M J, Silva D M, Oliveira A M, Ramalho L N
Department of Pathology and Legal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP Brazil.
Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP Brazil.
Diabetol Metab Syndr. 2017 Oct 13;9:82. doi: 10.1186/s13098-017-0282-5. eCollection 2017.
Non-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin-angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH.
C57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks. Glycemic and insulin levels, hepatic lipid profile, histological parameters and inflammatory protein expression were analyzed.
Aliskiren normalized plasma glucose and insulin levels, reduced cholesterol, triglycerides and total fat accumulation in liver and diminished hepatic injury, steatosis and fibrosis. These results could be explained by the ability of aliskiren to block angiotensin-II, lowering oxidative stress and inflammation in liver. Also, it exhibited a beneficial effect in increasing insulin sensitivity.
These findings support the use of aliskiren in the treatment of metabolic syndrome underlying conditions. However, clinical studies are indispensable to test its effectiveness in the treatment of patients with metabolic syndrome.
非酒精性脂肪性肝炎(NASH)与代谢综合征高度相关,代谢综合征是全球化社会中发病的主要原因。肾素-血管紧张素系统(RAS)影响肝脏脂肪酸代谢、炎症和纤维化。因此,在本研究中,我们旨在评估直接肾素抑制剂阿利吉仑对代谢综合征相关NASH的影响。
将45只C57BL/6雄性小鼠分为三组:对照组;用链脲佐菌素(STZ)(40mg/kg/天)接种5天并给予高脂饮食(HFD)8周的动物;用STZ接种5天、给予HFD 8周并在最后2周用阿利吉仑(100mg/kg/天)治疗的动物。分析血糖和胰岛素水平、肝脏脂质谱、组织学参数和炎症蛋白表达。
阿利吉仑使血糖和胰岛素水平正常化,降低肝脏中的胆固醇、甘油三酯和总脂肪积累,并减轻肝损伤、脂肪变性和纤维化。这些结果可以通过阿利吉仑阻断血管紧张素-II、降低肝脏氧化应激和炎症的能力来解释。此外,它在提高胰岛素敏感性方面表现出有益作用。
这些发现支持使用阿利吉仑治疗潜在的代谢综合征。然而,临床研究对于测试其在治疗代谢综合征患者中的有效性是必不可少的。