2型糖尿病大鼠脑组织TIPE2的表达特征及其与Aβ1-40沉积的相关性

目的   探讨2型糖尿病大鼠脑组织肿瘤坏死因子α诱导蛋白8样因子2（TIPE2）的表达特征及其与淀粉样蛋白Aβ1-40的相关性。方法   GK大鼠为2型糖尿病模型组（GK组），Wistar大鼠为非糖尿病模型组（Wistar组）。运用免疫组织化学染色法检测脑组织TIPE2和Aβ1-40的表达及空间分布；RT-PCR法和Western blot法分别检测脑组织TIPE2 mRNA水平和蛋白含量；ELISA法检测脑组织Aβ1-40蛋白含量。结果   TIPE2主要表达于皮层和皮层下组织结构的神经胶质细胞和微/小血管管壁。与Wistar组相比，GK组大鼠脑组织TIPE2蛋白、mRNA、阳染血管数和阳染神经胶质细胞数均显著增高（P均＜0.05）。Aβ1-40主要分布于皮质和海马等组织结构的神经元、神经胶质细胞和血管壁。与Wistar组相比，GK组大鼠脑组织Aβ1-40蛋白、阳染血管数和阳染细胞数均显著增高（P均＜0.05）。脑组织TIPE2蛋白表达与Aβ1-40水平在Wistar组（r=0.951）和GK组（r=0.954）均呈正相关（P均＜0.05）。结论   糖尿病大鼠脑组织TIPE2表达增多，并且与Aβ1-40沉积有关，提示TIPE2可能参与糖尿病脑组织损伤的发生发展。

Expression of TIPE2 and its association with Aβ1-40 deposition in brain tissue of type 2 diabetic GK rat

Objective   To investigate the expression of tumor necrosis factor-α induced protein-8 like-2 (TIPE2) and its association with amyloid beta 1-40 deposition in brain tissue of type 2 diabetic GK rat. Methods    GK rats were selected as type 2 diabetic rat model (GK group), and Wistar rats were selected as non-diabetic rat model (Wistar group). Then the spatial distribution of TIPE2 and Aβ1-40 in brain tissue was observed by immunohistochemistry (IHC). The mRNA and protein level of TIPE2 in brain tissue was detected by RT-PCR and Western blot respectively. The expression of Aβ1-40 in brain tissue was quantized by ELISA. Results   TIPE2 was observed in neuroglial cells and small blood vessels of cerebral cortex and subcortical structures in rat brain tissue. Compared to Wistar group, the expression of TIPE2 in brain tissue was significantly higher in GK group (P＜0.05). Aβ1-40 was detected in neurons, neuroglial cells, and brain blood vessel wall of cerebral cortex and hippocampus. Compared to Wistar group, expression of Aβ1-40 in brain tissue was significantly higher in GK group (P＜0.05). The expression of TIPE2 was positively associated with Aβ1-40 level both in Wistar group（r=0.951, P＜0.05） and GK group （r=0.954, P＜0.05）. Conclusion   TIPE2 expression in brain from type 2 diabetic GK group increases significantly than Wistar control group and is positively associated with Aβ1-40 deposition, indicating the role of TIPE2 in diabetic brain damage.