Mechanism of JAK2-STAT3 signaling pathway in ischemic postconditio-ning neuroprotection after cerebral ischemia in tree shrews / 中国病理生理杂志

ABSTRACT

AIM:To investigate the regulatory effect of JAK 2-STAT3 signaling pathway on the neuroprotection of ischemic postconditioning (IPoC) in tree shrews, and to explore the mechanisms of cerebral injury deterioration after in-hibiting the JAK2-STAT3 pathway .METHODS:The model of thrombotic cerebral ischemia was induced by photochemical reaction in tree shrews and the IPoC was established at 4 h after ischemia followed by clipping ipsilateral common carotid ar-tery on the ischemia side for 5 min ( 3 times ) .After IPoC and intracerebroventricular injection of AG 490 ( JAK2 inhibi-tor), the changes of cerebral infarction area were detected by TTC staining , and the histological and ultrastructural changes of cortical neurons were observed under light and electron microscopes , respectively .The protein levels of t-STAT3 and p-STAT3 in the cortical tissue were determined by Western blot .RESULTS:The neuronal pycnosis , mitochondrial swelling and vanish of the mitochondrial cristae were found in cortical cortex , and the infarction area was (24.78 ±3.30)%at 24 h after cerebral ischemia .Meanwhile, the phosphorylation level of STAT 3 protein in the cortical tissue was significantly in-creased (P<0.01).The cortical neuronal damage and mitochondrial swelling were decreased after IPoC , the area of cere-bral infarction was significantly reduced to (17.67 ±1.83)%(P<0.01), and the phosphorylation level of STAT3 protein was further increased ( P<0.01 ) .However , the neuronal damage was aggravated , the infarction area was expanded to (23.85 ±2.77)%(P<0.05) after treatment with AG490, and the phosphorylation level of STAT3 protein was also signif-icantly reduced ( P <0.05 ) .CONCLUSION: IPoC may reduce cerebral injury by regulating the phosphorylation of STAT3 protein, and inhibition of JAK2-STAT3 signaling pathway may counteract the cerebral protective effect of IPoC and aggravate brain injury .