自发性2型糖尿病模型OLETF大鼠肝肾纤维化的影响因素分析  

Relevant Factors of Kidney and Liver Fibrosis in OLETF Spontaneous Type 2 Diabetic Rat Model

作　　者：路晓光[1,2] 李平[2] 张浩军[2] 董晞[2] 杨丽平[2] 王康[2] 赵婷婷[2] 沙洪[2] 

机构地区：[1]北京中医药大学,北京100029 [2]中日友好医院临床医学研究所,北京100029

出　　处：《中国中西医结合肾病杂志》2010年第10期857-861,941,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家重点基础研究发展计划("973计划")基金资助项目(No.2005CB523503);科技部国际科技合作计划基金资助项目(No.2006DFB31480);首都医学科技发展基金资助项目(No.2005-S-Ⅰ-015)

摘　　要：目的:观察2型自发性糖尿病OLETF大鼠肾、肝纤维化的影响因素及其相互联系。方法:本实验将15只2型糖尿病OLETF大鼠作为模型组,将与其遗传背景相同但不发生糖尿病的15只LETO大鼠作为空白对照;分别在36周龄和56周龄两个时间点检测实验大鼠的体重、24h尿蛋白定量、血生化及血液流变学指标,并在光镜下半定量评价肾脏、肝脏纤维化程度,采用多元线性回归的方法分析肾、肝纤维化与各检测指标的关系。结果:OLETF大鼠在36周龄和56周龄均出现不同程度的肝肾纤维化,与空白组比较差异具有统计学意义(P<0.05);36周龄实验大鼠小管间质纤维化指数与24h尿蛋白定量和肾小球硬化指数线性相关,肾小球硬化指数与小管间质纤维化指数线性相关,肝脏胶原面积与24h尿蛋白定量线性相关;56周龄实验大鼠肾小球硬化指数与血糖和血浆黏度线性相关,小管间质纤维化指数与血糖、三酰甘油、全血黏度(高切)线性相关,肝脏胶原面积与血脂和全血黏度(低切)线性相关。结论:在动物实验早期,大鼠肾、肝纤维化均与24h尿蛋白定量线性相关;实验晚期肾脏纤维化受血糖影响更为显著,而肝脏纤维化与血脂关系更为密切;OLETF大鼠肝肾病理改变及其影响因素与人类相似,是研究2型糖尿病及其并发症的良好模型。Objective：To investigate the relevant factors of kidney and liver fibrosis in rats with diabetes.Methods：Fifteen spontaneous type 2 diabetic OLETF rats were used as the model group,and 15 LETOs with the similar genetic background but without diabetes were used as the control group.The body weight,24-hour urinary protein,blood biochemical and hemorheology parameters were examined at 36 and 56 weeks of age.Liver and renal fibrosis were examined under light microscope;the relationship between the fibrosis and the parameters was analyzed by multiple regression analysis.Results：There were significant renal and liver fibrosis in OLETF rats both at 36 and 56 weeks of age,compared with that in LETO rats,P0.05.At 36 weeks of age,the state of renal interstitial fibrosis was correlated with 24 h urinary protein and glomerular sclerosis,and there was a close relationship between glomerular sclerosis and renal interstitial fibrosis.Interestingly,liver fibrosis was also correlated with 24 h urinary protein.At 56 weeks of age,there was linear correlation between glomerular sclerosis and blood glucose and plasma viscosity.Blood glucose,triglycerides and blood viscosity 94.5 were the relevant factors for renal interstitial fibrosis.At last,liver fibrosis was associated with blood lipid and blood viscosity 0.945.Conclusion：There was close linear relationship of 24 h urinary protein level with renal and liver fibrosis at 36 weeks of age;and at 56 weeks of age,renal fibrosis was relevant to blood glucose,and there was a close relationship between serum lipid and liver fibrosis.The pathological changes and relevant factors of renal and liver fibrosis in OLETF rats were similar to those of the human beings.OLETF was a good animal model for the study of type 2 diabetes and its complications.

关 键 词：2型糖尿病 肝肾纤维化 OLETF大鼠 多元线性回归分析 

分 类 号：R587.1[医药卫生—内分泌]