Tao Xuelei, Xie Lili, Duan Chengwei, Dai Shirong, Ren Jianbing, Yan Yaohua, Shen Jianhong, Lu Hongjian, Ge Jianbin
Department of Neurosurgery, Nantong Second People's Hospital Affiliated to Nantong University, Nantong, 226001, Jiangsu Province, China.
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu Province, China.
Neurochem Res. 2016 Nov;41(11):2937-2947. doi: 10.1007/s11064-016-2012-z. Epub 2016 Jul 22.
Interferon regulatory factor 3 (IRF3) is a member of IRF family which plays a significant role in the innate immune response, apoptosis, and oncogenesis. Mounting evidence has demonstrated that IRF3 was involved in central nervous system disease such as cerebral ischemic injury through promoting neuronal apoptosis. However, it remains unclear about the underlying mechanisms of IRF3 upon neuronal apoptosis following intracerebral hemorrhage (ICH). In the present study, we established an adult rat ICH model by injecting autologous whole blood into the right basal ganglia and evaluated their neurological deficits by behavioral tests. IRF3 protein level was up-regulated adjacent to the hematoma following ICH when compared with the sham brain cortex by western blot and immunohistochemistry. Immunofluorescent staining indicated IRF3 was mainly localized in neurons, a few in astrocytes. In addition, we also detected that IRF3 co-localized with active caspase-3 which is a neuronal apoptosis marker. Furthermore, in vitro study, knocking down IRF3 by using IRF3 interference in primary cortical neurons reduced the expression of active caspase-3 and Bax while increased Bcl-2. In conclusion, we speculated that IRF3 might exert pro-apoptotic function in neurons after ICH.
干扰素调节因子3（IRF3）是IRF家族的成员，在先天免疫反应、细胞凋亡和肿瘤发生中起重要作用。越来越多的证据表明，IRF3通过促进神经元凋亡参与中枢神经系统疾病，如脑缺血损伤。然而，脑出血（ICH）后IRF3对神经元凋亡的潜在机制仍不清楚。在本研究中，我们通过向成年大鼠右侧基底神经节注射自体全血建立ICH模型，并通过行为测试评估其神经功能缺损。通过蛋白质免疫印迹和免疫组织化学检测发现，与假手术组脑皮质相比，ICH后血肿周围IRF3蛋白水平上调。免疫荧光染色表明，IRF3主要定位于神经元，少数定位于星形胶质细胞。此外，我们还检测到IRF3与神经元凋亡标志物活化的半胱天冬酶-3共定位。此外，在体外研究中，通过使用IRF3干扰剂敲低原代皮质神经元中的IRF3，可降低活化的半胱天冬酶-3和Bax的表达，同时增加Bcl-2的表达。总之，我们推测IRF3可能在ICH后神经元中发挥促凋亡作用。
