■安宫牛黄湾(AGNHW),在清朝(18世纪)发展,用于治疗严重感染引起的意识障碍,已被用于治疗缺血再灌注引起的脑水肿。然而,目前尚不清楚AGNHW是否能改善脂多糖(LPS)引起的血管源性脑水肿.本研究探讨了AGNHW对LPS诱导的小鼠脑水肿的改善作用。以及潜在的潜在机制。
■通过两次腹腔注射LPS(15mg/kg)在雄性C57BL/6N小鼠中建立脑血管水肿模型,在0和24小时。AGNHW通过管饲法以0.2275g/kg的剂量施用,0.455g/kg,和0.91克/千克,LPS给药后2h。在对照小鼠中,腹腔注射NS后2h,灌胃给予生理盐水(NS)或AGNHW(0.455g/kg)。存活率,脑含水量,脑静脉FITC-葡聚糖渗漏,埃文斯蓝外渗,血管内皮钙粘蛋白(VE-cadherin)的表达,闭塞带-1(ZO-1),claudin-5,磷酸化小窝蛋白-1(CAV-1),并评估了细胞膜和细胞质水通道蛋白1(AQP1)和水通道蛋白4(AQP4)。脑组织磷酸蛋白质组,AGNHW代谢物的血液水平,并分析了这些血液代谢产物与差异磷酸化蛋白之间的关系。
■AGNHW抑制LPS诱导的存活率降低,脑含水量增加,VE-Cadherin表达减少,磷酸化CAV-1(P-CAV-1)增加。AGNHW处理增加了LPS打针后星形细胞膜上AQP4的表达。AGNHW还抑制了LPS诱导的21种蛋白质的磷酸化增加,包括蛋白激酶C-α(PKC-α)和丝裂原活化蛋白激酶1(MAPK1),在脑组织中。在血液中检测到11种AGNHW代谢物。这些代谢物可能通过调节PKC-α和MAPK1发挥治疗作用。
■AGNHW可以改善LPS引起的脑血管水肿。这种作用与VE-Cadherin减少和CAV-1磷酸化的抑制有关,以及AQP4在星形胶质细胞膜上的表达上调,LPS注射后。
UNASSIGNED: Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms.
UNASSIGNED: A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (
AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed.
UNASSIGNED: AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of
AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1.
UNASSIGNED: AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of
AQP4 expression on the astrocyte membrane, following LPS injection.