2型糖尿病db/db小鼠肾脏动态病理特点
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摘要
目的:探讨2型糖尿病db/db小鼠肾脏动态病理特点,阐明其糖尿病肾病的发生发展机制,为糖尿病肾脏并发症的研究提供实验依据。方法:选取SPF级7~8周龄雄性db/db小鼠(模型组)和同龄雄性db/m小鼠(正常组)各16只,分别于8、16和32周龄时检测2组小鼠体质量和空腹血糖(FBG)水平,每组各处死小鼠8只,取肾组织行HE和Masson染色观察其病理形态表现,电镜下观察其超微结构。结果:与正常组比较,模型组小鼠8、16和32周龄时体质量增大(P<0.01),FBG水平明显升高(P<0.01),双肾指数明显降低(P<0.01);32周时模型组小鼠双肾指数明显低于16周时(P<0.05)。HE和Masson染色,16周龄时模型组小鼠肾组织可见明显病理改变,主要是肾小球体积增大和肾小管上皮细胞明显水肿;32周龄时病变明显加重,肾组织中可见大量蓝染胶原物质。电镜观察,16周龄时模型组小鼠肾组织以肾小球基底增厚、足突融合、肾小管上皮细胞线粒体数目减少及形态肿胀为主;32周龄时病变明显加重,可见大量胶原纤维。结论:16周龄糖尿病db/db小鼠肾脏有明显病理改变,主要是肾小球基底增厚、足突融合,32周龄时小鼠肾组织呈明显纤维化。
Objective:To investigate the dynamic pathological characteristics of kidney in the db/db mice with type 2 diabetes mellitus and to clarify the pathogenesis and development mechanism of diabetic nephropathy,and to provide the experimental evidence for the further study on diabetic nephropathy.Methods:The male SPF db/db mice aged 7-8 weeks were selected as model group(n=16)and the db/m mice with the same ages were selected as control group(n=16).The body weights and levels of fasting blood glucose(FBG)of the mice were detected after 8,16,and 32 weeks.Then eight mice in each group were sacrificed and the kidney tissue was dissected at 8,16 and 32 weeks.HE and Masson staining were used to observe the pathomorphology of the kidney tissue;the ultrastructures of kidney tissue were observed under electron microscope.Results:Compared with normal group,the body weights of the mice in model group at 8,16 and 32 weeks were significantly increased(P<0.01),the FBG levels were significantly increased(P<0.01),and the double kidney indexes were significantly decreased(P<0.01);the double kidney index of the mice in model group at 32 weeks was lower than that at 16 weeks(P<0.05).The HE and Masson staining results showed that the morphological changes of kidney tissue of the mice at16 weeks were significant,the glomerular volume was expansion and the kidney tubular epithelial cells were edema,which turned serious at 32 weeks.A large number of blue dye substances in the kidney tissue was found.Under electron microscope,the glomerular basement membranes got thickened,the foot processes got fused and the number of mitochondria in kidney tubular epithelial cells was reduced and swell was found in the mice in model group at 16 weeks;the lesions in the kidney tissue were serious at 32 weeks,and the collagenous fiber was visible at32 weeks.Conclusion:The pathological changes in the kidney tissue of the db/db mice at 16 weeks are significant,such as glomerular basement thickening and footwork fusion.The kidney tissue of the db/db mice at 32 weeks shows prominent fibrosis.
Objective:To investigate the dynamic pathological characteristics of kidney in the db/db mice with type 2 diabetes mellitus and to clarify the pathogenesis and development mechanism of diabetic nephropathy,and to provide the experimental evidence for the further study on diabetic nephropathy.Methods:The male SPF db/db mice aged 7-8 weeks were selected as model group(n=16)and the db/m mice with the same ages were selected as control group(n=16).The body weights and levels of fasting blood glucose(FBG)of the mice were detected after 8,16,and 32 weeks.Then eight mice in each group were sacrificed and the kidney tissue was dissected at 8,16 and 32 weeks.HE and Masson staining were used to observe the pathomorphology of the kidney tissue;the ultrastructures of kidney tissue were observed under electron microscope.Results:Compared with normal group,the body weights of the mice in model group at 8,16 and 32 weeks were significantly increased(P<0.01),the FBG levels were significantly increased(P<0.01),and the double kidney indexes were significantly decreased(P<0.01);the double kidney index of the mice in model group at 32 weeks was lower than that at 16 weeks(P<0.05).The HE and Masson staining results showed that the morphological changes of kidney tissue of the mice at16 weeks were significant,the glomerular volume was expansion and the kidney tubular epithelial cells were edema,which turned serious at 32 weeks.A large number of blue dye substances in the kidney tissue was found.Under electron microscope,the glomerular basement membranes got thickened,the foot processes got fused and the number of mitochondria in kidney tubular epithelial cells was reduced and swell was found in the mice in model group at 16 weeks;the lesions in the kidney tissue were serious at 32 weeks,and the collagenous fiber was visible at32 weeks.Conclusion:The pathological changes in the kidney tissue of the db/db mice at 16 weeks are significant,such as glomerular basement thickening and footwork fusion.The kidney tissue of the db/db mice at 32 weeks shows prominent fibrosis.
引文
[1]刘芳,杨华,周文江,等.诱发性2型糖尿病小鼠模型与自发性db/db小鼠特性的比较[J].中国实验动物学报,2014,22(6):54-59.
[2]黄海燕,王利则,于燕,等.丹参联合罗格列酮对db/db糖尿病小鼠肝纤维化的干预作用[J].中国老年学杂志,2012,32(10):2082-2084.
[3]陆洁,刘静,裴天仙,等.自发性2型糖尿病模型db/db小鼠生物学特性研究[J].药物评价研究,2013,36(5):341-345.
[4]刘静,陆洁,裴天仙,等.基因缺陷型2型糖尿病模型动物db/db小鼠早期生物学特性研究[J].药物评价研究,2013,36(8):8-12.
[5]邢玮,王政霖,吕甜甜,等.2型糖尿病db/db小鼠的生物学特性[J].中国比较医学杂志,2017,27(8):12-15.
[6]郑丽阳,薛瑞,吕婷婷,等.三七皂苷Fc对2型糖尿病db/db小鼠肾脏保护作用研究[J].中华中医药学刊,2017,35(3):609-611.
[7]金智生,王东旭,张花治,等.红芪多糖对db/db小鼠糖尿病心肌病TGF-B/Smads信号通路影响的实验研究[J].北京中医药大学学报,2017,40(1):20-26.
[8]Piccoli GB,Grassi G,Cabiddu G,et al.Diabetic kidney disease:a syndrome rather than a single disease[J].Rev Diabet Stud,2015,12(1/2):87-109.
[9]Zhang L,Liu J,Zhou F,et al.PGC-1αameliorates kidney fibrosis in mice with diabetic kidney disease through an antioxidative mechanism[J].Mol Med Rep,2018,17(3):4490-4498.
[10]Lindblom R,Higgins G,Coughlan M,et al.Targeting mitochondria and reactive oxygen species-driven pathogenesis in diabetic nephropathy[J].Rev Diabet Stud,2015,12(1/2):134-156.
[11]李娟娥,王磊,秦灵灵,等.自发性2型糖尿病啮齿类动物模型研究概况[J].中国实验方剂学杂志,2010,16(6):267-271.
[12]郑丽阳,薛瑞,吕亭亭,等.三七皂苷Fc对2型糖尿病db/db小鼠的肾脏保护作用研究[J].中华中医药学刊,2017,35(3):609-611.
[13]邢玮,王政霖,吕甜甜,等.2型糖尿病db/db小鼠的生物学特性[J].中国比较医学杂志,2017,27(8):12-15.
[14]金智生,魏玉娇,林海龙,等.红芪多糖对早期糖尿病肾病db/db小鼠肾间质纤维化的影响[J].北京中医药大学学报,2017,40(8):677-683.
[15]Shaw JE,Sicree RA,Zimmet PZ.Global estimates of the prevalence of diabetes for 2010and 2030[J].Diabetes Res Clin Pract,2010,87(1):4-14.
[16]Aggarwal PK,Veron D,Thomas DB,et al.Semaphorin3a promotes advanced diabetic nephropathy[J].Diabetes,2015,64(5):1743-1759.
[17]童国玉,朱大龙.糖尿病肾病国内外临床指南和专家共识解读[J].中国实用内科杂志,2017,37(3):211-216.
[18]胡承.糖尿病肾病遗传机制研究现状与研究策略[J].中国实用内科杂志,2017,37(3):207-210.
[19]Jia ZH,Liu ZH,Zheng JM,et al.Combined therapy of rhein and benazepril on the treatment of diabetic nephropathy in db/db mice[J].Exp Clin Endocrinol Diabetes,2007,115(9):571-576.
[2]黄海燕,王利则,于燕,等.丹参联合罗格列酮对db/db糖尿病小鼠肝纤维化的干预作用[J].中国老年学杂志,2012,32(10):2082-2084.
[3]陆洁,刘静,裴天仙,等.自发性2型糖尿病模型db/db小鼠生物学特性研究[J].药物评价研究,2013,36(5):341-345.
[4]刘静,陆洁,裴天仙,等.基因缺陷型2型糖尿病模型动物db/db小鼠早期生物学特性研究[J].药物评价研究,2013,36(8):8-12.
[5]邢玮,王政霖,吕甜甜,等.2型糖尿病db/db小鼠的生物学特性[J].中国比较医学杂志,2017,27(8):12-15.
[6]郑丽阳,薛瑞,吕婷婷,等.三七皂苷Fc对2型糖尿病db/db小鼠肾脏保护作用研究[J].中华中医药学刊,2017,35(3):609-611.
[7]金智生,王东旭,张花治,等.红芪多糖对db/db小鼠糖尿病心肌病TGF-B/Smads信号通路影响的实验研究[J].北京中医药大学学报,2017,40(1):20-26.
[8]Piccoli GB,Grassi G,Cabiddu G,et al.Diabetic kidney disease:a syndrome rather than a single disease[J].Rev Diabet Stud,2015,12(1/2):87-109.
[9]Zhang L,Liu J,Zhou F,et al.PGC-1αameliorates kidney fibrosis in mice with diabetic kidney disease through an antioxidative mechanism[J].Mol Med Rep,2018,17(3):4490-4498.
[10]Lindblom R,Higgins G,Coughlan M,et al.Targeting mitochondria and reactive oxygen species-driven pathogenesis in diabetic nephropathy[J].Rev Diabet Stud,2015,12(1/2):134-156.
[11]李娟娥,王磊,秦灵灵,等.自发性2型糖尿病啮齿类动物模型研究概况[J].中国实验方剂学杂志,2010,16(6):267-271.
[12]郑丽阳,薛瑞,吕亭亭,等.三七皂苷Fc对2型糖尿病db/db小鼠的肾脏保护作用研究[J].中华中医药学刊,2017,35(3):609-611.
[13]邢玮,王政霖,吕甜甜,等.2型糖尿病db/db小鼠的生物学特性[J].中国比较医学杂志,2017,27(8):12-15.
[14]金智生,魏玉娇,林海龙,等.红芪多糖对早期糖尿病肾病db/db小鼠肾间质纤维化的影响[J].北京中医药大学学报,2017,40(8):677-683.
[15]Shaw JE,Sicree RA,Zimmet PZ.Global estimates of the prevalence of diabetes for 2010and 2030[J].Diabetes Res Clin Pract,2010,87(1):4-14.
[16]Aggarwal PK,Veron D,Thomas DB,et al.Semaphorin3a promotes advanced diabetic nephropathy[J].Diabetes,2015,64(5):1743-1759.
[17]童国玉,朱大龙.糖尿病肾病国内外临床指南和专家共识解读[J].中国实用内科杂志,2017,37(3):211-216.
[18]胡承.糖尿病肾病遗传机制研究现状与研究策略[J].中国实用内科杂志,2017,37(3):207-210.
[19]Jia ZH,Liu ZH,Zheng JM,et al.Combined therapy of rhein and benazepril on the treatment of diabetic nephropathy in db/db mice[J].Exp Clin Endocrinol Diabetes,2007,115(9):571-576.