| 糖尿病大鼠肾组织差异表达的AGE-修饰蛋白 |
| Alternative Title | The research on AGE-modified proteins differentially expressed in renal tissues of diabetic rats
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| 王璐 |
| Thesis Advisor | 汤旭磊
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| 2015-05-21
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| Degree Grantor | 兰州大学
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| Place of Conferral | 兰州
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| Degree Name | 硕士
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| Keyword | 糖尿病
糖尿病肾损伤
晚期糖基化终末产物
蛋白质
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| Abstract | 目的：分析和鉴定糖尿病大鼠肾脏中AGE-修饰蛋白，为糖尿病肾病的诊断和治疗探索新的分子标志物。
方法：SPF级 8周龄雄性SD大鼠随机分为糖尿病1月、3月组及正常组，STZ腹腔注射建立糖尿病大鼠模型；光镜及电镜下观察肾脏结构改变；ELISA测定肾脏AGE-修饰蛋白浓度，1-DE/ Western Blot分离肾脏AGE-修饰蛋白；quantity-one4.6.2分析肾脏AGE-修饰蛋白的表达差异； MALDI-TOF-MS鉴定差异表达的AGE-修饰蛋白。
结果：糖尿病1月组大鼠主要表现为系膜区的增宽，糖尿病3月组大鼠系膜区增宽较1月组明显，且出现了基底膜的增厚。糖尿病1月及3月组大鼠肾脏AGE-修饰蛋白浓度高于正常组（p＜0.05，p＜0.001），糖尿病3月组大鼠肾脏AGE-修饰蛋白浓度高于1月组（p＜0.001）。糖尿病组大鼠肾肾脏AGE-修饰蛋白浓度与血糖浓度正相关（r=0.4303, p =0.025）。4种AGE-修饰蛋白在糖尿病组大鼠肾脏的表达高于正常组，在糖尿病3月组的表达高于1月组，分别是：肌动蛋白、血清转铁蛋白、过氧化氢酶及血清白蛋白。
结论：糖尿病组大鼠肾脏中AGE-修饰蛋白的浓度及表达水平增加，且与糖尿病病程相关。4种AGE-修饰蛋白的表达上调，分别是：肌动蛋白、血清转铁蛋白、过氧化氢酶及血清白蛋白。糖基化可能影响了这些蛋白质的结构及功能，导致糖尿病的肾脏损伤，具体机制尚待进一步研究。 |
| Other Abstract | Objective To analyze and identify the AGE-modified proteins in renal tissues of diabetic rats and explore novel molecular markers for early diagnosis and treatment of patients with diabetic nephropathy.Methods SPF male SD rats were randomly divided into three groups: diabetic rats for 1month and 3months. healthy group; the morphological changes in renal tissues of rats were observed with light and electron microscopes; the concentrations of AGE-modified proteins in renal tissues of rats were measured by ELISA kit; the AGE-modified proteins were separated by 1-DE and western blot; the AGE-modified protein bands differentially expressed were analyzed through quantity-one 4.6.2software,which was analyzed by MALDI-TOF-MS.Results The glomerular mesangial area of focal segmental of diabetic rats for 1 month expanded,mainly an increase in mesangial matrix,with or without mesangial cell proliferatin compared with normal rats;the changes of mesangial area with diabetic rats for 3 months were more obvious,and focal segmental capillary basement member thickening appeared in diabetic rats for 3 months. the concentrations of AGEs in renal tissues of 1 month and 3 months diabetic rats[(420.9±53.0) ug/ml and (618.8±86.1)ug/ml, respectively] were significantly（p＜0.05, p＜0.001 respectively） higher than which of normal rats[（332.3±51.4）ug/ml], the concentrations of AGEs of 3 months diabetic rats[(618.8±86.1)ug/ml] were significantly （p＜0.001） higher than which of 1 month[(420.9±53.0)ug/ml]. Pearson correlation analysis showed the concentrations (ug/ml) of AGE-modified proteins in renal tissues of diabetic rats were positively correlated with blood glucose concentration. four AGE-modified proteins in diabetic rats were upregulated compared with the control group，in addition,the expression of these four proteins in diabetic rats for 3 months were significantly higher than which of 1 month. the AGE-modified proteins which were upregulated in renal tissues of diabetic rats were:actin, serotransferrin, catalase, serum Albumin.Conclusion The concentration and levels of AGE-modified proteins in renal tissues of diabetic rats were increased,which were related with the duration of diabetes mellitus.four AGE-modified proteins were identified: actin, serotransferrin, catalase, serum albumin.glycosylation may affect the structure and function of these proteins and lead to diabetic kidney damage,the specific mechanism for which needs to be further studied. |
| URL | 查看原文
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| Language | 中文
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| Document Type | 学位论文
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| Identifier | https://ir.lzu.edu.cn/handle/262010/222660
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| Collection | 学院待认领
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| Affiliation | 临床医学院
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Recommended Citation
GB/T 7714 |
王璐. 糖尿病大鼠肾组织差异表达的AGE-修饰蛋白[D]. 兰州. 兰州大学,2015.
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