关键词: 内质网应激, 糖尿病脑病, 葡萄糖调节蛋白78, CCAAT/增强子结合蛋白同源蛋白, 海马

Abstract:

Objective To observe the changes in expression of glucose-regulating protein 78(GRP78) and CCAAT/enhancer-binding protein homologous protein(CHOP) in the hippocampal CA1 region of mice with diabetic encephalopathy, and to explore the important role of endoplasmic reticulum stress (ER Stress) in the pathogenesis of diabetic encephalopathy.
Methods Sixty male mice were divided into a normal control group(n=25) and a diabetes mellitus(DM) group(n=35). Streptozocin（STZ）was freshly prepared and injected at 200 mg/kg, i.p. into mice which had been fasted for 12 h. At 1 week, 4 weeks and 8 weeks after STZ administration, immunohistochemistry was performed with GRP78 and CHOP antibodies. The numbers of GRP78 and CHOP positive cells were measured by imaging analysis software. Data was expressed as mean±standard deviation(SD).
Results ① The result of GRP78 antibody immunohistochemical staining showed that the morphology and numbers of GRP78-positive cells in hippocampal CA1 region of DM group mice at 1 week, 4 weeks and 8 weeks after STZ injection were similar to those of normal control group mice. ② Immunohistochemical staining with CHOP antibody at 1 week, 4 weeks and 8 weeks after STZ injection showed that normal control group mice had few lightlystained CHOPpositive cells in hippocampal CA1 region, while DM group mice had more darkly stained CHOP-positive cells in
hippocampalCA1 region. ③ At 1 week, 4 weeks and 8 weeks after STZ injection, the numbers of GRP78-positive cells in the hippocampal CA1 region of DM group mice（12.00±3.60, 10.50±3.11, 13.75±3.01） showed no significant difference(P=0.29, P=0.23, P=0.06) compared with those of normal control group mice(10.33±2.34, 8.88±1.89, 7.00±3.2). The numbers of CHOP-positive cells in the hippocampal CA1 region of DM group mice at 1 week, 4 weeks and 8 weeks after STZ injection(45.12±10.27, 32.88±6.58, 20.19±3.54) increased significantly(P=0.000, P=0.000, P=0.009) compared with those of normal control group mice（19.19±6.80, 15.44±5.35, 13.94±5.00）.
Conclusion The expression level of ER Stress related molecule CHOP in hippocampal CA1 region of diabetic encephalopathy mice was increased compared with that of normal mice. The hippocampus of diabetic encephalopathy mice underwent ER Stress. ER Stress might play an important role in the pathogenesis of neuronal degeneration of diabetic encephalopathy.

Key words: endoplasmic reticulum stress, diabetic encephalopathy, glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, hippocampus