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 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.
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。