C1型尼曼-匹克氏症小鼠的肾脏功能及病理变化  

Renal function and pathological changes in Niemann-Pick disease type C1 mice

作　　者：刘彦礼[1,2] 乔梁[1,2] 张金珠[1] 杨芬[1] 闫岩 闫欣[1] 林俊堂[1,2] 

机构地区：[1]新乡医学院生命科学技术学院 [2]河南省医用组织再生重点实验室,河南新乡453003

出　　处：《中国病理生理杂志》2016年第8期1435-1439,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81400936);国家自然科学基金-河南人才培养联合基金资助项目(No.U1304808);河南省高等学校重点科研项目计划(No.15A180009)

摘　　要：目的:探讨Npc1基因突变小鼠肾脏功能及病理生理的变化,为C1型尼曼-匹克氏症(NPC1)患者临床上药物的使用及肾功能的维持提供理论依据。方法:用PCR法确定小鼠基因型;选取出生后第60天(P60)的野生型NCPC1(Npc1^(+/+))和突变型NCPC1(Npc1^(-/-))小鼠,检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH)的活性及尿素(Urea)、尿酸(UA)和肌酐(Cr)的含量来评价Npc1-/-小鼠的肝肾功能变化;进一步常规冷冻切片后通过β-半乳糖苷酶染色及Masson染色来分别评价Npc1^(-/-)小鼠肾脏衰老及纤维化情况。结果:与P60的Npc1^(+/+)小鼠相比,Npc1^(-/-)小鼠的体重和肾脏重量显著降低(P<0.01);肝肾功能明显减退:ALT、AST及LDH活性显著升高(P<0.05),Urea、UA及Cr的含量显著增加(P<0.05);冷冻切片染色结果表明肾脏组织衰老明显(P<0.01),纤维化程度显著增强(P<0.01)。结论:Npc1基因突变导致的脂质异常代谢可加速肾间质纤维化,促使肾脏衰老,最终导致肾功能减退。AIM： To investigate the renal function and pathological changes in Npc1 mutant（Npc1^（-/-）） mice.METHODS： Different genotypes of Niemann-Pick disease type C1（ Npc1） mice were identified by PCR. Subsequently,the renal function of Npc1^（-/-） and Npc1^（＋/＋）mice at postnatal day 60（ P60） was evaluated by measuring the activity and content of important indicators in the serum including ALT,AST,LDH,urea,UA and Cr. Furthermore,β-galactosidase staining and Masson staining were performed to examine the aging and fibrosis of the renal tissues,respectively. RESULTS：Compared with the Npc1^（＋/＋）mice,the body weight and kidney weight had a significant reduction（ P 0. 01） in the Npc1^（-/-）mice. The results of hepatic and renal functions showed that the activities of ALT,AST and LDH,and contents of urea,UA and Cr had marked increases（ P 0. 05） in the Npc1^（-/-）mice. Moreover,the results of senescence-associated β-galactosidase staining in the renal tissues demonstrated accelerated aging in the Npc1^（-/-）mice（ P 0. 01）,and these results were confirmed by Masson staining,which clearly showed the formation of collagen fibers（ P 0. 01）. CONCLUSION： Mutation of the Npc1 gene results in abnormal lipid metabolism,which accelerates kidney senescence by promoting fibrosis in the renal tissue and subsequently causes reduction in renal function.

关 键 词：C1型尼曼-匹克氏症 肾脏 纤维化 Npc1基因 

分 类 号：R363[医药卫生—病理学]