背景:青少年倾向于尝试使用乙醇,这通常会导致严重的间歇性饮酒模式,从而在以后的生活中引起严重的健康问题。长期使用乙醇会损害肾组织,促进胶原蛋白沉积,并诱发肾脏炎症,从而导致肾功能障碍。因此,可以抑制乙醇对肾脏的影响的干预措施,例如辛伐他汀(一种降低血液胆固醇的药物)可能是有益的。这项研究探讨了辛伐他汀对肾脏形态损害发作的影响,纤维化,和小鼠乙醇暴露引起的炎症。
方法:将10只四周大的C57BL/6J小鼠(F=5;M=5)分配到每个实验组:(I)NT;不给药乙醇或辛伐他汀;(II)EtOH;2.5g/kg/天的20%乙醇;腹膜内注射(i.p.)(III);SIM/kg/天的辛伐他汀;口服(iv/5口头,然后是2.5g/kg/天的20%乙醇;i.p.和(v)EtOH+SIM15;15mg/kg/天的辛伐他汀,口头,然后是2.5g/kg/天的20%乙醇;在28天的治疗期后,右肾被切除并处理苏木精和伊红染色,马森三色染色,或肿瘤坏死因子-α(TNF-α)免疫组织化学。肾红细胞区,肾小球面积,测量尿隙面积,并使用ImageJ软件定量胶原蛋白或TNF-α表达的面积。
结果:乙醇给药显著增加肾脏红细胞面积,肾小球面积,胶原蛋白的面积,和具有TNF-α免疫反应性的组织面积,但减少了尿液空间的面积。辛伐他汀通常抑制男女的乙醇效应,虽然程度不同。
结论:辛伐他汀可以抑制乙醇诱导的小鼠肾脏中胶原沉积和TNF-α的产生,从而表明其在治疗乙醇相关肾脏疾病中的有效性。
BACKGROUND: Adolescents tend to experiment with ethanol which often results in heavy episodic drinking patterns leading to serious health concerns later in life. Chronic ethanol use damages renal tissue, promotes collagen deposition, and induces renal inflammation, thereby causing renal dysfunction. Therefore, an intervention such as simvastatin (a blood cholesterol-lowering drug) that could suppress the effects of ethanol on the kidney may be beneficial. This study explored the impact of simvastatin against the onset of renal morphological damage, fibrosis, and inflammation caused by ethanol exposure in mice.
METHODS: Ten four-week old C57BL/6J mice (F = 5; M = 5) were assigned to each experimental group: (I) NT; no administration of ethanol or simvastatin; (II) EtOH; 2.5 g/kg/day of 20% ethanol, intraperitoneal injection (i.p.); (III) SIM; 5 mg/kg/day of simvastatin, orally; (IV) EtOH + SIM5; 5 mg/kg/day of simvastatin, orally, followed by 2.5 g/kg/day of 20% ethanol, i.p.; and (V) EtOH + SIM15; 15 mg/kg/day of simvastatin, orally, followed by 2.5 g/kg/day of 20% ethanol, i.p. After the 28-day treatment period, the right kidney was removed and processed for haematoxylin and eosin staining, Masson\'s trichrome staining, or tumour necrosis factor-alpha (TNF-α) immunohistochemistry. The renal corpuscular area, glomerular area, and urinary space area were measured and the area of collagen or TNF-α expression was quantified using ImageJ software.
RESULTS: Ethanol administration significantly increased the renal corpuscular area, the glomerular area, the area of collagen, and the area of tissue with TNF-α immunoreactivity but decreased the area of urinary space. Simvastatin generally suppressed the ethanol effects in both sexes, although to varying degrees.
CONCLUSIONS: Simvastatin proved to suppress collagen deposition and the TNF-α production induced by ethanol in the kidney of mice thus indicating its effectiveness in the treatment of ethanol-related renal diseases.