Bai Xue, Xiong Liu-Lin, Fang Chang-Le, Zhou Hao-Li, Xue Lu-Lu, Hu Yue, Xia Qing-Jie, Liu Jia, Zhang Jun-Yan, Wang Ting-Hua, Yang Si-Jin
Department of Cardiac and Cerebral Diseases, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China.
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide 5000, Australia.
Anal Cell Pathol (Amst). 2021 Jun 2;2021:6622713. doi: 10.1155/2021/6622713. eCollection 2021.
Interleukin 10 (IL-10) is a synthetic inhibitor of human cytokines with immunomodulatory and anti-inflammatory effects. This study was designed to investigate the expression variation of IL-10 in the multiple sites including cortex, hippocampus, and lung tissues of neonatal hypoxic-ischemic (HI) rats and explore the crucial role of IL-10 in alleviating HI brain damage. In this study, neonatal Sprague-Dawley rats were subjected to the right common carotid artery ligation, followed by 2 h of hypoxia. The expression of IL-10 in the cortex, hippocampus, and lung tissues was measured with immunohistochemistry, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot (WB). Immunofluorescence double staining was performed to observe the localization of IL-10 in neurons and astrocytes. Moreover, not-targeting and targeting IL-10 siRNA lentivirus vectors were injected into the rats of the negative control (NC) and IL-10 group, respectively, and the mRNA levels of B-cell lymphoma 2 (Bcl-2) and endoplasmic reticulum protein 29 (ERp29) were detected by RT-qPCR following IL-10 silence. The results demonstrated that the IL-10 expression was markedly increased after HI and IL-10 were colocalized with neurons and astrocytes which were badly injured by HI insult. In addition, Bcl-2 and ERp29 were remarkably decreased following IL-10 mRNA interference compared with the NC group. Our findings revealed that IL-10 exerted its antiapoptotic and neuroprotective effects by regulating the expression of Bcl-2 and ERp29, indicating that IL-10 may be a promising molecule target for HIE treatment.
白细胞介素10（IL-10）是一种具有免疫调节和抗炎作用的人细胞因子合成抑制剂。本研究旨在探讨新生缺氧缺血（HI）大鼠皮质、海马和肺组织等多个部位IL-10的表达变化，并探讨IL-10在减轻HI脑损伤中的关键作用。在本研究中，对新生Sprague-Dawley大鼠进行右侧颈总动脉结扎，随后进行2小时缺氧。采用免疫组织化学、实时定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法（WB）检测皮质、海马和肺组织中IL-10的表达。进行免疫荧光双染色以观察IL-10在神经元和星形胶质细胞中的定位。此外，分别将非靶向和靶向IL-10的小干扰RNA慢病毒载体注入阴性对照组（NC）和IL-10组大鼠体内，在IL-10沉默后通过RT-qPCR检测B细胞淋巴瘤2（Bcl-2）和内质网蛋白29（ERp29）的mRNA水平。结果表明，HI后IL-10表达明显增加，且IL-10与受HI损伤严重的神经元和星形胶质细胞共定位。此外，与NC组相比，IL-10 mRNA干扰后Bcl-2和ERp29明显降低。我们的研究结果表明，IL-10通过调节Bcl-2和ERp29的表达发挥其抗凋亡和神经保护作用，表明IL-10可能是治疗新生儿缺氧缺血性脑病（HIE）的一个有前景的分子靶点。
