CAJ | 학술논문

目的本研究采用高脂饮食诱导肥胖大鼠模型,观察肾小球足细胞Podocin的变化及其在导致蛋白尿中的作用.方法实验大鼠分正常对照组(Con组)和肥胖组(Ob组).在造模14周时,分别检测体重、身长、尾长、肾重、尿蛋白、尿RBP、尿肌酐、血糖、血脂、血尿酸(UA)、血肌酐(Cre)、血尿素氮(BUN)及血浆胰岛素,计算Lee's指数、组织胰岛素抵抗、胰岛素敏感性指数、内生肌酐清除率(Ccr)、相对肾重,用光学显微镜、电子显微镜等观察肾脏形态变化,用免疫组织化学和Western blot方法,检测肥胖大鼠肾小球足细胞Podocin的表达.结果 ①0周时Ob组与Con组比较性别、体重、身长、尾长,Lee's指数等差异无统计学意义(P＞0.05)；14周时Ob组体重、身长,Lee's指数明显高于Con组,差异有统计学意义(P＜0.05).②14周时Ob组与Con组比较空腹血糖升高,高密度脂蛋白降低,差异有统计学意义(P＜0.05).2组间UA、Cre、BUN等差异无统计学意义(P＞0.05).③Ob组在14周时尿蛋白和Ccr明显高于Con组,差异有统计学意义(分别P＜0.05,P＜0.01).④Ob组与Con组比较肾重无明显差异,Ob组相对肾重＜ Con组(P＜0.05).⑤光镜下Ob组可见肾皮质区肾小球肥大,肾小囊狭窄,节段性毛细血管闭塞,球囊粘连.电镜下Ob组肾脏肾小球足细胞呈粗大状,足突轻度微绒毛化.⑥免疫组化染色和Western blot检测Ob组肾小球足细胞Podocin蛋白表达比Con组减少,差异有统计学意义(t值为17.24；P＜0.001).结论肥胖大鼠肾小球足细胞Podocin蛋白的表达减少,伴有足细胞超微结构的改变,可能是其产生蛋白尿的原因之一.
목적 본연구채용고지음식유도비반대서모형,관찰신소구족세포Podocin적변화급기재도치단백뇨중적작용.방법 실험대서분정상대조조(Con조)화비반조(Ob조).재조모14주시,분별검측체중、신장、미장、신중、뇨단백、뇨RBP、뇨기항、혈당、혈지、혈뇨산(UA)、혈기항(Cre)、혈뇨소담(BUN)급혈장이도소,계산Lee's지수、조직이도소저항、이도소민감성지수、내생기항청제솔(Ccr)、상대신중,용광학현미경、전자현미경등관찰신장형태변화,용면역조직화학화Western blot방법,검측비반대서신소구족세포Podocin적표체.결과 ①0주시Ob조여Con조비교성별、체중、신장、미장,Lee's지수등차이무통계학의의(P＞0.05)；14주시Ob조체중、신장,Lee's지수명현고우Con조,차이유통계학의의(P＜0.05).②14주시Ob조여Con조비교공복혈당승고,고밀도지단백강저,차이유통계학의의(P＜0.05).2조간UA、Cre、BUN등차이무통계학의의(P＞0.05).③Ob조재14주시뇨단백화Ccr명현고우Con조,차이유통계학의의(분별P＜0.05,P＜0.01).④Ob조여Con조비교신중무명현차이,Ob조상대신중＜ Con조(P＜0.05).⑤광경하Ob조가견신피질구신소구비대,신소낭협착,절단성모세혈관폐새,구낭점련.전경하Ob조신장신소구족세포정조대상,족돌경도미융모화.⑥면역조화염색화Western blot검측Ob조신소구족세포Podocin단백표체비Con조감소,차이유통계학의의(t치위17.24；P＜0.001).결론 비반대서신소구족세포Podocin단백적표체감소,반유족세포초미결구적개변,가능시기산생단백뇨적원인지일.
Objective To discuss the mechanism of obesity related glomerularpathology,we detect the expression of Podocin in glomerular podocytes of obesity rats induced by high fat diet.Methods The rats were divided into 2 groups:normal control group(Con group) and obesity group(Ob group).At the 14th week of molding,the body weight,body long,tail long,kidney weight,uria microalbumin,RBP,uria Cre,blood glucose,cholesterol,triglyceride,HDL-C,UA,Cre,BUN,and insulin were measured.The Lee's index,insulin resistance index,insulin sensitive index,Ccr and relative kidney weight were calculated.The tissue structures of the kidney of both groups were studied under light microscope and transmission electro microscope.The expression of Podocin in podocyte of rats' kidney was measured by immunohistochemistry and western blot.Results ①The difference had no statistical significance between the 2 groups in gender,weight,body length,tail length and Lee's index at the beginning (P ＞ 0.05).But after 14 weeks,the weight,body length and Lee's index of Ob group were significantly higher than those of Con group(P ＜0.05).②At the 14th week,the fasting plasma glucose of Ob group was higher than that of Con group (P ＜ 0.05),and the high density lipoproteins (HDL) of Ob group was lower than that of Con group(P ＜ 0.05).However,the difference had no statistical significance in urine acid (UA),serum Cre and blood urea nitrogen (BUN) between the 2 groups (P ＞ 0.05).③The urine protein and endogenous creatinine clearance rate(Ccr) in Ob group were higher than those of Con group (P ＜ 0.05,P ＜0.01).④The relative kidney weight of Ob group was lower than that of Con group(P ＜ 0.05).⑤For rats in Ob group,glomerular hypertrophy,the Bowman' capsule stricture,abnormality in the segmental capillary wall and extraglomerular mesangial cell were observed under light microscope.The glomerular podocytes became broader and foot process of podocyte in Ob group became microvillus-like in Ob group under transmission electro microscope.⑥Immunohistochemistry and western blot showed that the expression of Podocin in podocyte of kidney decreased in Ob group.Conclusions The expression of Podocin decreased in podocyte of kidney in obesity rats.At the same time,the ultrastructure of podocytes was changed.Those may be one of the reasons for protein urine related to obesity.