中文摘要
Cx43主要位于星形胶质细胞,在脑缺血损伤和修复过程中起重要作用。补阳还五汤是中医药领域治疗脑缺血的经典名方,前期研究发现它在脑缺血急性期有效抑制星形胶质细胞Cx43,在修复期却有上调作用。补阳还五汤对脑缺血后Cx43的双相调节机制是临床治疗脑缺血的关键科学问题。结合文献和预实验结果,本项目推测:脑缺血急性期补阳还五汤通过抑制炎症因子的释放降低星形胶质细胞Cx43减轻损伤;修复期补阳还五汤通过bFGF增强星形胶质细胞Cx43,促进神经修复和血管再生。本研究拟通过基因、蛋白和功能多个水平深入探讨补阳还五汤在脑缺血不同时期对Cx43的影响,从分子、组织和在体实验探讨补阳还五汤在脑缺血急性期和修复期调节Cx43的机制,并阐明Cx43在补阳还五汤减轻脑缺血损伤和促进修复中的作用机理。本研究以Cx43为切入点,旨在科学阐述补阳还五汤治疗脑缺血的独特优势(趋其利避其害),为临床治疗脑缺血提供新的思路。
英文摘要
Connexin43 (Cx43) which was mainly located in astrocytes plays an important role in both damage and repairing process after cerebral ischemia. Buyang Huanwu decoction (BYHWD) is a classical prescription for treatment of cerebral ischemia in traditional Chinese medicine. Our previous studies found that BYHWD could efficiently inhibit the expression of Cx43 in astrocytes in acute stage of cerebral ischemia, but up-regulated it in reparing stage. The dual regulation of Cx43 by BYHWD is a pivotal problem in clinical treatment of cerebral ischemia. Combined with previous studies and preliminary results, we speculated as the followings: in acute stage of cerebral ischemia, BYHWD down-regulated astrocytic Cx43 by inhibition of inflammatory cytokines thus reducing infarction; In reparing stage, BYHWD enhanced Cx43 in astrocytes via bFGF so promoting nerve repairment and angiogenesis. This study intends to investigate the effect of BYHWD on Cx43 at multiple levels (gene, protein and function) in different periods after cerebral ischemia, explore the mechanisms of BYHWD affecting Cx43 from the level of molecular, histology and in vivo animals in both acute and reparing stage after cerebral ischemia, and clarify the roles of Cx43 in reducing ischemic injury and promoting repairment of BYHWD. Based on Cx43, this study aims to scientifically explain the unique advantage of BYHWD for treating cerebral ischemia (reserving its advantages and getting rid of its harmful effects), which provides new evidence for clinical treatment of cerebral ischemia.
