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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
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)
