Ma Yi, Sun Shihui, Zhang Jingwen, Chen Zhirong, Guo Fengying, Du Yanhui, Zhang Jianzhong
Department of Pathology, and Ningxia Key Lab of Craniocerebral Disease, Ningxia Medical University, Yinchuan, 750004, China.
Department of Neurology, General Hospital, Ningxia Medical University, Yinchuan, 750004, China.
Neurochem Res. 2016 Apr;41(4):787-94. doi: 10.1007/s11064-015-1753-4. Epub 2015 Nov 26.
Previous studies have demonstrated that the c-Jun N-terminal kinase (JNK) pathway plays an important role in inducing neuronal apoptosis following cerebral ischemic injury. JNK signaling pathway in activated during cerebral ischemic injury. It participates in ischemia-induced neuronal apoptosis. However, whether JNK signaling is involved in the process of neuronal apoptosis of diabetes-induced cerebral ischemia is largely unknown. This study was undertaken to evaluate the influence of cerebral ischemia-reperfusion injury on phosphorylation of JNK in diabetic rats. Twenty-four adult streptozotocin induced diabetic and 24 adult non-diabetic rats were randomly subjected to 15 min of forebrain ischemia followed by reperfusion for 0, 1, 3, and 6 h. Sixteen sham-operated diabetic and non-diabetic rats were used as controls. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Protein expression of phospho-JNK was examined by immunohistochemistry and Western blot. The numbers of TUNEL-positive cells and phospho-JNK protein expression in the cerebral cortices after 1, 3 and 6 h reperfusion was significantly higher in diabetic rats compared to non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). Western blot analysis showed significantly higher phospho-JNK protein expression in the cerebral cortices of the diabetic rats after 1 and 3 h reperfusion than that was presented in non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). These findings suggest that increased phosphorylation of JNK may be associated with diabetes-enhanced ischemic brain damage.
先前的研究表明，c-Jun氨基末端激酶（JNK）通路在脑缺血损伤后诱导神经元凋亡过程中起重要作用。JNK信号通路在脑缺血损伤时被激活，参与缺血诱导的神经元凋亡。然而，JNK信号是否参与糖尿病性脑缺血的神经元凋亡过程在很大程度上尚不清楚。本研究旨在评估脑缺血再灌注损伤对糖尿病大鼠JNK磷酸化的影响。将24只成年链脲佐菌素诱导的糖尿病大鼠和24只成年非糖尿病大鼠随机进行15分钟的前脑缺血，随后分别再灌注0、1、3和6小时。16只假手术的糖尿病和非糖尿病大鼠作为对照。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）评估细胞凋亡。通过免疫组织化学和蛋白质印迹法检测磷酸化JNK的蛋白表达。与经历缺血再灌注的非糖尿病动物相比，糖尿病大鼠再灌注1、3和6小时后，大脑皮质中TUNEL阳性细胞数量和磷酸化JNK蛋白表达显著更高（p<0.05）。蛋白质印迹分析显示，再灌注1和3小时后，糖尿病大鼠大脑皮质中磷酸化JNK蛋白表达显著高于经历缺血再灌注的非糖尿病动物（p<0.05）。这些发现表明，JNK磷酸化增加可能与糖尿病增强的缺血性脑损伤有关。
