摘要
目的探讨ＫＫＡ ｙ 小鼠作为２型糖尿病动物模型在肾脏病研究方面的价值。方法８周龄的雄性ＫＫＡｙ 小鼠（ｎ＝１５）和Ｃ５７ＢＬ－Ｊ小鼠（ｎ＝１８），于１６、２０、２４周处死动物。尾静脉取血测血糖（血糖仪试纸法），全自动生化分析仪测定血ＬＤＬ、ＴＧ、ＣＨＯ、Ｃｒ 、ＢＵＮ，放免方法测血胰岛素水平。用三氯醋酸比浊法测定２４ｈ尿蛋白浓度，不同病理染色方法了解其肾脏病理改变与蛋白尿的关系。用北京航空航天大学计算机中心提供的医学彩色图象分析软件分析。结果不同周龄的ＫＫＡｙ小鼠的体重、血糖（Ｐ＜０．０１），血浆胰岛素水平、血甘油三酯、胆固醇和低密度脂蛋白水平都比同龄Ｃ５７ＢＬ小鼠高（Ｐ＜０．０５）。而血肌酐、尿素氮差异无显著性。２０，２４周时ＫＫＡｙ小鼠的尿蛋白浓度较同龄Ｃ５７ＢＬ小鼠也显著升高（Ｐ＜０．００５）。ＫＫＡｙ小鼠的肾小球面积普遍比Ｃ５７ＢＬ小鼠大，系膜基质增加，肾小管腔扩大，管壁变薄，肾小球基底膜增厚，还可以见到蛋白管型、小管灶状萎缩。结论ＫＫＡｙ小鼠１６周龄以后出现高血糖、高胰岛素血症、高脂血症，伴有尿蛋白增加，和肾小球系膜基质增加，肾小球基底膜增厚和小管扩张，是较好的研究２型糖尿病肾脏早期发病的动物模型?
Objective To investigate the early pathological changes of KKAy mouse model of type2diabetes.Methods Five male KKA ymice and six C57BL mice each were studied at the age of8,16,20and24weeks.With each mouse a24-hour urine collection was made for the tests of protein-uria.Plasma insulin,lipids,serum creatinine and urea were also measured.Renal tissues were obse-rved to assess glomerular and tubulointerstial pathology.Results The KKAy mice developed hypergly-cemia,hyperinsulinemia and obesity by16weeks of age(P<0.01).The proteinuria increased with the increasing of age(P<0.005),but there were no changes in control.The glomerular hypertrophy was observed in KKAy mice at the age of16weeks.Computer map analysis system(CMIAS)indicated the expansion of mesangial matrix in KKAy mice with ageing.There was significant tubular dilation,accompanied with focal tubular atrophy and interstitial fibrosis.On electron microscopy,GBM undergo progressive thickening(P<0.01),accompanied with podocytes fusion and increasing of proteinuria.Conclusions KKAy mice developed hyperglycemia,hyperinsulinemia and obesity after16weeks,with proteinuria,mesangial matrix accumulation,GBM thickening and tubular dilation.It was considered a good animal model for the early pathology changes of DN.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2002年第1期71-75,I001-I002,共7页
Acta Academiae Medicinae Sinicae
