本文關(guān)鍵詞： 腎移植 腎機能不全 移植物存活 胰島素 代謝綜合征X 疾病模型 動物 組織工程 組織構(gòu)建 慢性移植腎失功 胰島素抵抗 代謝綜合征 動物模型 腎功能 尿蛋白 腎臟病理 國家自然科學(xué)基金　出處：《中國組織工程研究》2017年12期 　論文類型：期刊論文

【摘要】：背景:慢性移植腎失功的主要病因迄今尚不明確,胰島素抵抗可能構(gòu)成其病因之一,然而當(dāng)前尚缺乏相關(guān)動物模型及實驗探討二者的關(guān)聯(lián)。目的:建立胰島素抵抗慢性移植腎失功大鼠模型,探討胰島素抵抗對移植腎腎功能、尿蛋白及病理學(xué)改變的影響。方法:在以F344及Lewis大鼠作為供受體的慢性移植腎失功模型基礎(chǔ)上予單純高脂飼料喂養(yǎng)誘發(fā)胰島素抵抗,分別于腎移植術(shù)后8,12,16周測定胰島素抵抗慢性移植腎失功組、慢性移植腎失功組、單腎切除對照組血胰島素、血糖、血肌酐、尿素氮及24 h尿蛋白,計算胰島素抵抗指數(shù)。同時行口服葡萄糖耐量及胰島素耐量試驗,分別計算血糖-時間曲線下面積,根據(jù)3組不同時間點胰島素抵抗指數(shù)、口服葡萄糖耐量及胰島素耐量試驗血糖-時間曲線下面積的差異評估胰島素抵抗慢性移植腎失功模型建成情況及穩(wěn)定性。比較胰島素抵抗慢性移植腎失功組與慢性移植腎失功組血肌酐、尿素氮及24 h尿蛋白的組間差異及不同時間點的差異,于16周行腎臟病理學(xué)觀察,根據(jù)Banff總評分比較3組腎臟病變程度的差異。結(jié)果與結(jié)論:(1)術(shù)后8,12,16周胰島素抵抗慢性移植腎失功組胰島素抵抗指數(shù)、口服葡萄糖耐量及胰島素耐量試驗血糖-時間曲線下面積均大于慢性移植腎失功組及對照組,且隨觀察時間延長無顯著改變,血肌酐、尿素氮、24 h尿蛋白均小于慢性移植腎失功組,亦隨觀察時間延長無顯著改變;(2)胰島素抵抗慢性移植腎失功組及慢性移植腎失功組均見腎小球及小管基底膜輕度增厚、間質(zhì)纖維化及動脈內(nèi)膜輕度增生等改變,但未見2組腎臟病變程度的顯著差異;(3)上述結(jié)果提示,使用單純高脂飼料喂養(yǎng)慢性移植腎失功大鼠8周可構(gòu)建穩(wěn)定的胰島素抵抗慢性移植腎失功模型,胰島素抵抗可能影響移植腎腎功能及尿蛋白水平,其潛在機制可能涉及胰島素抵抗環(huán)境下腎小球的高濾過及腎小管對尿蛋白的超負(fù)荷重吸收。
[Abstract]:Background: the main causes of chronic renal allograft dysfunction are still unclear, and insulin resistance may be one of its causes. However, there is still a lack of related animal models and experimental study on the relationship between them. Objective: to establish a model of chronic renal allograft dysfunction in rats with insulin resistance, and to explore the effect of insulin resistance on renal function. Methods: on the basis of chronic renal allograft failure model with F344 and Lewis rats as donor recipients, insulin resistance was induced by high fat diet alone. Serum insulin, blood glucose, serum creatinine, urea nitrogen and 24 h urine protein were measured in chronic allograft failure group, chronic allograft failure group and single nephrectomy control group at 812 weeks after renal transplantation. The insulin resistance index was calculated. Oral glucose tolerance test and insulin tolerance test were used to calculate the area under the glycemic time curve, and the insulin resistance index was calculated according to the different time points in the three groups. The difference of the area under the blood glucose curve between oral glucose tolerance test and insulin tolerance test the establishment and stability of chronic renal allograft failure model of insulin resistance were compared between chronic insulin resistance renal allograft failure group and chronic renal allograft failure group. Serum creatinine in patients with renal allograft dysfunction, The difference of urea nitrogen and 24 h urine protein and the difference of different time points were observed at 16 weeks. Results and conclusion the insulin resistance index of chronic renal allograft failure group was 812 ~ 16 weeks after operation. The area under the glycemic time curve of oral glucose tolerance test and insulin tolerance test was larger than that of chronic renal allograft failure group and control group. Urinary protein in 24 h of urea nitrogen group was lower than that in chronic allograft group, and there was no significant change with the prolongation of observation time) glomerular and tubule basement membrane thickened slightly in both chronic allograft and chronic allograft failure group, and insulin resistance group showed slight thickening of glomerular and microtubule basement membrane. Interstitial fibrosis and mild intimal hyperplasia, but no significant difference in the degree of renal lesions between the two groups. A stable model of chronic renal allograft failure with insulin resistance could be established by feeding chronic allograft dysfunction rats with high fat diet for 8 weeks. Insulin resistance may affect renal function and urinary protein level. The underlying mechanism may involve high filtration of glomeruli and overloaded reabsorption of urinary proteins by renal tubules in insulin-resistant environment.
【作者單位】： 南方醫(yī)科大學(xué);南方醫(yī)科大學(xué)第三附屬醫(yī)院腎內(nèi)科泌尿疾病研究所;南方醫(yī)科大學(xué)第三附屬醫(yī)院檢驗科;深圳市人民醫(yī)院腎內(nèi)科;
【基金】：國家自然科學(xué)基金(81270840)~~
【分類號】：R-332;R699.2
，

本文編號：1541728