Chu Heling, Huang Chuyi, Gao Zidan, Dong Jing, Tang Yuping, Dong Qiang
Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai, 200040, China.
Department of Neurology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200336, China.
Phytother Res. 2017 Sep;31(9):1410-1418. doi: 10.1002/ptr.5868. Epub 2017 Jul 28.
Paeoniflorin (PF) and astragaloside IV (AS-IV) have protective effects on cerebral ischemia. We aimed to test the effects of combined use of PF and AS-IV on ischemic brain edema and investigate whether the effects were dependent on connexin43 (Cx43). We detected the expression of Cx43 induced by PF and AS-IV after cerebral ischemia. We also examined the effects of combined use of PF and AS-IV on ischemic edema and further investigated the related pathways. We demonstrated PF and AS-IV decreased Cx43 and aquaporin4 (AQP4) associating with reduction of brain edema by dry-wet weight and brain-specific gravity methods after cerebral ischemia. Administration of PF and AS-IV displayed a further attenuation of brain edema with lower Cx43 levels. Meanwhile, Cx43 blockade inhibited AQP4 down-regulation by the two drugs. Moreover, phosphorylation of C-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) were increased by PF and AS-IV, respectively. The effects of PF and AS-IV to down-regulate Cx43 were suppressed by JNK and ERK inhibitors, respectively. Our data indicate that PF and AS-IV alleviate ischemic brain edema, which has close relation to Cx43 down-regulation causing decrease of AQP4 via JNK and ERK pathways activation, respectively. Combined administration elicits synergistic effects on brain edema reduction. Copyright © 2017 John Wiley & Sons, Ltd.
芍药苷（PF）和黄芪甲苷（AS-IV）对脑缺血具有保护作用。我们旨在测试PF和AS-IV联合使用对缺血性脑水肿的影响，并研究其作用是否依赖于连接蛋白43（Cx43）。我们检测了脑缺血后PF和AS-IV诱导的Cx43表达。我们还研究了PF和AS-IV联合使用对缺血性水肿的影响，并进一步探究相关途径。我们通过干湿重法和脑比重法证明，PF和AS-IV可降低Cx43和水通道蛋白4（AQP4）的表达，进而减轻脑水肿。给予PF和AS-IV可进一步减轻脑水肿，且Cx43水平更低。同时，阻断Cx43可抑制这两种药物对AQP4的下调作用。此外，PF和AS-IV分别增加了C-Jun氨基末端激酶（JNK）和细胞外信号调节激酶（ERK）的磷酸化。JNK和ERK抑制剂分别抑制了PF和AS-IV下调Cx43的作用。我们的数据表明，PF和AS-IV可减轻缺血性脑水肿，这与通过分别激活JNK和ERK途径下调Cx43导致AQP4减少密切相关。联合给药对减轻脑水肿具有协同作用。版权所有© 2017约翰威立父子有限公司。
