Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Biomed Pharmacother. 2018 Jul;103:614-620. doi: 10.1016/j.biopha.2018.04.069. Epub 2018 Apr 24.
Previous studies indicated that cerebral ischemia/reperfusion injury (CI/RI) could induce behavioral deficits. Single treatment of vagus nerve stimulation (VNS) or curcumin is reported to restore CI/RI-induced behavioral deficits. However, the synergic effect remains unclear.
Rats were divided into 6 groups: sham, CI/RI, VNS, CI/RI + VNS, VNS + curcumin and CI/RI + VNS + curcumin groups. Each group was further divided into three or four subgroups for further assessments. In specific, Morris water maze task and shuttle box test were used to evaluate cognitive capacity. Rota-rod test, neurological deficits scores, 2,3,5-triphenyltetrazolium chloride staining, TUNEL staining were performed to estimate motor capacity, neurological deficits, the size of infarct volume and neural apoptosis, respectively. Finally, the expressions of apoptosis-associated proteins and key kinases in the AKT/extracellular signal-regulated kinase-2 (ERK2) pathway were measured by Western blot analysis.
Combination of curcumin and VNS significantly restored the CI/RI-induced cognitive and motor impairments compared with the CI/RI + VNS group (P < 0.05 and P < 0.01). Moreover, combination of curcumin and VNS significantly lowered CI/RI-induced neurological deficits, infract volume, neural apoptosis (all P < 0.05) and inflammatory cytokines release (P < 0.05 and P < 0.01) when compared to the CI/RI + VNS group. Additionally, the phosphorylation levels of AKT and ERK2 were both increased by combination of curcumin and VNS compared with the CI/RI + VNS group.
Combination of curcumin and VNS restored CI/RI-induced behavioral deficits by inhibiting apoptosis and inflammatory response. Besides, the AKT/ERK2 pathway might be implicated.
先前的研究表明，脑缺血/再灌注损伤（CI/RI）可导致行为缺陷。已有研究报道，单一使用迷走神经刺激（VNS）或姜黄素治疗可恢复 CI/RI 诱导的行为缺陷。然而，协同作用尚不清楚。
将大鼠分为 6 组：假手术组、CI/RI 组、VNS 组、CI/RI+VNS 组、VNS+姜黄素组和 CI/RI+VNS+姜黄素组。每组进一步分为 3 或 4 个亚组进行进一步评估。具体而言，使用 Morris 水迷宫任务和穿梭箱测试评估认知能力。通过转棒测试、神经缺陷评分、2,3,5-三苯基氯化四氮唑染色、TUNEL 染色分别评估运动能力、神经缺陷、梗死体积大小和神经细胞凋亡。最后，通过 Western blot 分析测量 AKT/细胞外信号调节激酶 2（ERK2）通路中与凋亡相关的蛋白和关键激酶的表达。
与 CI/RI+VNS 组相比，姜黄素和 VNS 的联合使用显著改善了 CI/RI 诱导的认知和运动障碍（P<0.05 和 P<0.01）。此外，与 CI/RI+VNS 组相比，姜黄素和 VNS 的联合使用显著降低了 CI/RI 诱导的神经功能缺损、梗死体积、神经细胞凋亡（均 P<0.05）和炎症细胞因子释放（P<0.05 和 P<0.01）。此外，与 CI/RI+VNS 组相比，姜黄素和 VNS 的联合使用增加了 AKT 和 ERK2 的磷酸化水平。
姜黄素和 VNS 的联合使用通过抑制细胞凋亡和炎症反应来恢复 CI/RI 诱导的行为缺陷。此外，AKT/ERK2 通路可能参与其中。
