The contents of Dynorphin A(1–8) decreased gradually in ischemic cortices in rats and an intracerebroventricular administration of synthetic Dynorphin A(1–8) reduced the volume of cerebral infarction in our previous research. However, the specific protective mechanism is unclear and Dynorphin A(1–8) is unlikely to cross the blood-brain barrier (BBB) by noninvasive oral or intravenous administration as a macromolecule neuropeptide. In this study, intranasal administration was used to middle cerebral artery occlusion(MCAO) rats to assessed the therapeutic effects of Dynorphin A(1–8) by evaluating behavior, volume of cerebral infarct, cerebral edema ratio, histological observation. Then apoptosis neuron rate was detected by TUNEL staining. Immunohistochemical staining was carried out to explore the alteration of Bcl-2, Bax and Caspase-3. Finally, κ-opioid receptor antagonist and N-methyl-d-aspartate(NMDA) receptor antagonist were used to explore its possible mechanism. We found that MCAO rats under intranasal administration of Dynorphin A(1–8) showed better behavioral improvement, higher extent of Bcl-2, activity of SOD along with much lower level of infarction volume, brain water content, number of cell apoptosis, extent of Bax and Caspase-3, and concentration of MDA compared with those in MCAO model group and intravenous Dynorphin A(1–8) group. Administration of nor-BNI or MK-801 reversed these neuroprotective effects of intranasal Dynorphin A(1–8). In summary, Dynorphin A(1–8), with advantages of intranasal administration, could be effectively delivered to central nervous system(CNS). Dynorphin A(1–8) inhibited oxidative stress and apoptosis against cerebral ischemia/reperfusion injury, affording neuroprotection through NMDA receptor and κ-opioid receptor channels.

在我们之前的研究中，大鼠缺血性皮质中强啡肽 A(1-8) 的含量逐渐减少，而合成强啡肽 A(1-8) 的脑室内给药减少了脑梗塞的体积。然而，具体的保护机制尚不清楚，强啡肽 A(1-8) 作为大分子神经肽通过无创口服或静脉给药不太可能穿过血脑屏障 (BBB)。本研究对大脑中动脉闭塞（MCAO）大鼠进行鼻内给药，通过评估行为、脑梗死体积、脑水肿率、组织学观察来评估强啡肽A（1-8）的治疗效果。然后用TUNEL染色检测神经元凋亡率。进行免疫组织化学染色以探索Bcl-2、Bax和Caspase-3的改变。最后，N-甲基-d采用-天冬氨酸(NMDA)受体拮抗剂探讨其可能作用机制。我们发现，经鼻给予强啡肽 A（1-8）的 MCAO 大鼠表现出更好的行为改善、更高程度的 Bcl-2、SOD 活性以及更低水平的梗塞体积、脑含水量、细胞凋亡数量、程度与 MCAO 模型组和静脉注射强啡肽 A(1-8) 组相比，Bax 和 Caspase-3 和 MDA 浓度。nor-BNI 或 MK-801 的给药逆转了鼻内强啡肽 A (1-8) 的这些神经保护作用。综上所述，强啡肽 A(1-8) 具有鼻内给药的优势，可有效输送至中枢神经系统 (CNS)。Dynorphin A(1-8) 抑制氧化应激和细胞凋亡对脑缺血/再灌注损伤，