Department of Pathology and Molecular Medicine Center, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, ZJ, P.R. China.
Department of Urinary Surgery, Zhejiang Chinese Medical University, Hangzhou, ZJ, P.R. China.
Transplant Proc. 2021 Jan-Feb;53(1):486-490. doi: 10.1016/j.transproceed.2020.06.032. Epub 2020 Aug 5.
The main cause of chronic renal allograft dysfunction (CRAD) still remains unclear. Insulin resistance (IR) may be a potential inducement, but there is insufficient evidence about this association. We aimed to establish a rat model of CRAD complicated with IR and to explore the function and pathologic changes of the renal allograft induced by IR.
F344-to-Lewis rats of CRAD were fed a high-fat diet to induce IR. They were divided into 3 groups: IR (CRAD+IR), CRAD, and control (CTL). Serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were measured to evaluate the renal function. The Homeostasis Model Assessment (HOMA)-IR index was detected by comparing the values of fasting serum insulin levels (FINS) with fasting blood glucose levels (FBG). The pathologic analysis was conducted by the degree of renal lesions including glomerular lesions, renal tubular lesions, hemorrhage, inflammatory cell infiltration, fibrillation, and hyperplasia of the renal interstitium.
In the second, third, and fourth month after surgery, serum levels of Scr and BUN in the IR group were reduced more than those in the CRAD group, while they were both higher compared to the CTL group, suggesting that renal function in the CRAD group was declined. The HOMA-IR in the IR group was greater than that in the CRAD and CTL groups, showing that simple high-fat diet feeding significantly and steadily increased FINS and FBG in CRAD complicated with IR rats. Pathologic changes indicated that the CRAD rat model was successfully constructed and was still in the early-middle stages of renal lesions 4 months after surgery, yet IR presented a significant effect on CRAD.
These results indicate that the stable CRAD complicated with IR rat model can be established through a high-fat diet in CRAD rats in 4 months, and IR could be an influencing factor.
慢性移植肾失功（CRAD）的主要原因仍不清楚。胰岛素抵抗（IR）可能是一个潜在的诱因，但关于这种关联的证据不足。我们旨在建立一个伴有 IR 的 CRAD 大鼠模型，并探讨 IR 对肾移植的功能和病理变化。
用高脂肪饮食喂养 F344 至 Lewis 大鼠以诱导 IR。将其分为 3 组：IR（CRAD+IR）、CRAD 和对照组（CTL）。通过测量血尿素氮（BUN）和血清肌酐（Scr）的水平来评估肾功能。通过比较空腹血清胰岛素（FINS）水平和空腹血糖（FBG）的值来检测稳态模型评估（HOMA-IR）指数。通过肾小球病变、肾小管病变、出血、炎性细胞浸润、纤维化和肾间质增生等肾脏病变程度进行病理分析。
手术后第 2、3、4 个月，IR 组的血清 Scr 和 BUN 水平较 CRAD 组下降，但均高于 CTL 组，提示 CRAD 组肾功能下降。IR 组的 HOMA-IR 高于 CRAD 和 CTL 组，表明单纯高脂饮食喂养可显著且稳定地增加 CRAD 合并 IR 大鼠的 FINS 和 FBG。病理变化表明成功构建了 CRAD 大鼠模型，并且在手术后 4 个月时仍处于肾病变的早中期，但 IR 对 CRAD 有显著影响。
这些结果表明，在 4 个月内可以通过 CRAD 大鼠的高脂肪饮食建立稳定的伴有 IR 的 CRAD 大鼠模型，并且 IR 可能是一个影响因素。
