Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage.
Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage.
复制标题
脑出血后，骨桥蛋白通过JAK2/STAT1途径通过JAK2/STAT1途径减轻炎症。
DOI：
10.1016/j.neuropharm.2018.06.009
复制
发表时间：
2018-08
影响因子：
4.7
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Gong L;Manaenko A;Fan R;Huang L;Enkhjargal B;McBride D;Ding Y;Tang J;Xiao X;Zhang JH
急性脑出血（ICH）合并高血糖与卒中后炎症加重相关，导致脑水肿加剧，并预示患者神经功能预后不良和死亡率升高。骨桥蛋白（OPN）是一种具有神经保护作用的糖蛋白，能够减轻出血性卒中引起的脑损伤。在本研究中，我们探讨了OPN是否会降低高血糖大鼠脑出血后的炎症反应，以及减轻脑水肿和神经功能缺损。我们采用胶原酶诱导雄性Sprague - Dawley大鼠（n = 148）脑出血模型，并在脑出血后3小时腹腔注射50%葡萄糖（ICH + HG）。在脑出血后1小时进行重组OPN（rOPN）鼻腔给药。通过脑含水量（BWC）、神经功能缺损、蛋白质印迹法和免疫组织化学研究评估脑损伤的发展。使用整合素 - β1受体的小干扰核糖核酸（siRNA）和一种JAK2激动剂——香豆霉素A1（C - A1）对分子通路进行详细研究。与ICH + HG组大鼠相比，给予OPN（3μg）显著改善了神经行为，增加了脑内OPN和整合素 - β1受体的表达，同时减少了ICH + HG + OPN组大鼠的中性粒细胞浸润、JAK2、STAT1、TNF - α、IL - 1β、MMP - 9和脑水肿。整合素 - β1 siRNA和C - A1的干预逆转了OPN的作用。总之，rOPN减轻了高血糖大鼠脑出血诱导的脑部炎症，从而减轻脑水肿并改善神经功能。rOPN的作用至少部分是通过整合素 - β1诱导的对JAK2/STAT1通路的抑制来介导的。
Acute intracerebral hemorrhage (ICH) complicated by hyperglycemia is associated with aggravation of post-stroke inflammation, leading to exacerbation of brain edema and predicting poor neurological outcomes and higher mortality of patients. Osteopontin (OPN) is a neuroprotective glycoprotein, which is able to attenuate brain injury induced by hemorrhagic stroke. In the current study we investigated whether OPN will decrease the inflammatory post-ICH response as well as attenuate brain edema and neurological deficits in hyperglycemic rats. We employed a collagenase model of ICH on male Sprague-Dawley rats (n = 148) rats and 50% of Dextrose was injected intraperitoneally (i.p) 3 h after ICH (ICH + HG). Intranasal administration of recombinant OPN (rOPN) was performed 1 h after ICH. The development of brain injury was evaluated by brain water content (BWC) and neurological deficits, western blot and immunohistochemistry study. Small interfering ribonucleic acid (siRNA) for integrin-β1 receptor and a JAK2 agonist, Coumermycin A1 (C-A1), were used for detailed investigation of the molecular pathway. The administration of OPN (3 μg) significantly improved neurobehavior and increased expression of OPN and integrin-β1 receptor in the brain followed with decrease of neutrophil infiltration, JAK2, STAT1, TNF-a, IL-1b, MMP-9 and brain edema in the ICH + HG + OPN rats compared with ICH + HG rats. The effects of OPN were reversed by the intervention of intergrin-β1 siRNA and C-A1. In conclusion, rOPN attenuated ICH-induced brain inflammation in hyperglycemic rats, leading to attenuation of brain edema and improving neurological functions. Effects of rOPN were mediated at least partly by integrin-β1 induced inhibition of JAK2/STAT1 pathway.
登录
查看更多内容
影响因子：
8.3
作者：
Wu J;Zhang Y;Yang P;Enkhjargal B;Manaenko A;Tang J;Pearce WJ;Hartman R;Obenaus A;Chen G;Zhang JH
通讯作者：
Zhang JH
影响因子：
3.7
作者：
Omoyinmi E;Standing A;Keylock A;Price-Kuehne F;Melo Gomes S;Rowczenio D;Nanthapisal S;Cullup T;Nyanhete R;Ashton E;Murphy C;Clarke M;Ahlfors H;Jenkins L;Gilmour K;Eleftheriou D;Lachmann HJ;Hawkins PN;Klein N;Brogan PA
通讯作者：
Brogan PA
影响因子：
2.6
作者：
Banks WA
通讯作者：
Banks WA
影响因子：
4.7
作者：
Xie Z;Huang L;Enkhjargal B;Reis C;Wan W;Tang J;Cheng Y;Zhang JH
通讯作者：
Zhang JH
影响因子：
8.3
作者：
Bejot, Yannick;Aboa-Eboule, Corine;Giroud, Maurice
通讯作者：
Giroud, Maurice