Seipin基因缺陷诱发小鼠肾损害

Seipin gene deficiency induces renal injury in mice

目的:探讨seipin基因缺陷对小鼠肾脏结构和功能的影响及其可能的发病机制。方法:选取6月龄C57BL/6遗传背景的seipin基因敲除和野生型雄鼠,检测seipin基因在野生型小鼠各组织的表达;检测2组小鼠肾功能和病理改变,以及脂肪相关因子的表达。结果:Seipin基因在脂肪及睾丸中高表达,肾脏可检测到低水平seipin的表达,主要位于肾小球。与野生型小鼠相比,seipin敲除小鼠尿白蛋白及肌酐清除率增高;肾小球表面积增大、肾基质增多;血浆脂联素和瘦素水平下降,出现胰岛素抵抗。结论:Seipin基因缺陷可导致小鼠肾损害,可能与全身脂肪缺失引起的脂联素和瘦素水平下降相关。

AIM： To investigate the effects of seipin gene deficiency on renal injury and the possible mechanisms in seipin- /-mice. METHODS： Six-month-old male seipin knockout（ seipin- /-） and wild-type（ WT） mice（ n =8） were used to study 24 h urinary albumin excretion（ UAE）,renal functions,pathological changes,and plasma leptin and adiponectin levels. Seipin mRNA expression in different tissues and each part of the kidney was also measured in WT mice. RESULTS： Real-time PCR analysis showed seipin mRNA expression in WT mice was higher in adipose tissue and testicles,and was also found in the kidney,which was mainly in glomeruli. Compared with control group,seipin- /-group showed increased kidney weight /tibia length（ P 〈0. 01）,24 h UAE（ P 〈0. 01）,creatinine clearance（ P 〈0. 01）,and glomerular and mesangial surface area（ P 〈0. 05）. Both plasma leptin（ P〈 0. 01） and adiponectin（ P 〈0. 05） levels were significantly decreased in seipin- /-mice. CONCLUSION： Seipin gene deficiency in mice leads to renal injury probably by decreasing plasma leptin and adiponectin levels due to lack of adipose tissue.