C3G通过PKA/CREB信号通路减轻成年小鼠SAH后早期脑损伤

目的 探讨矢车菊素-3-O-葡萄糖苷（C3G）对小鼠蛛网膜下腔出血（SAH）后早期脑损伤（EBI）的影响及作用机制。方法 取72只雄性C57小鼠随机分成6组:假手术组、SAH组、溶剂组、低剂量C3G组（10 mg/kg）、中剂量C3G组（（20 mg/kg）、高剂量C3G组（30 mg/kg）；每组12只。应用颈动脉穿刺法制作小鼠SAH模型，术后24 h进行Garcia评分和平衡木评分评估神经功能；每组小鼠随机取6只取外周血检测活性氧（ROS）和丙二醛（MDA）含量，然后取出完整脑组织进行SAH出血评分、脑水含量检测；每组剩余6只小鼠取外周血检测GSH/GSSG水平，然后取脑组织应用免疫印迹法检测PKA、p-PKA、CREB、p-CREB和GCLC表达水平。结果 与假手术组相比，SAH组小鼠神经功能评分明显下降（P<0.05），脑水含量、SAH出血评分、外周血ROS和MDA含量均显著增加（P<0.05），外周血GSH/GSSG比值明显下降（P<0.05），脑组织p-PKA、p-CREB和GCLC表达明显上调（P<0.05）。C3G明显增加小鼠神经功评分（P<0.05），明显降低SAH评分降低、脑含水量（P<0.05），明显降低外周血ROS、MDA含量（P<0.05），明显增加外周血GSH/GSSG比值（P<0.05），明显下调脑组织p-PKA、p-CREB和GCLC表达（P<0.05）。结论 C3G明显改善小鼠SAH后EBI，其机制可能是抑制PKA/CREB信号通路，下调GCLC表达，进而抑制氧化应激损伤。

Cyanidin-3-O-glucoside attenuates early brain injury after subarachnoid hemorrhage in adult mice through PKA/CREB signaling pathway

Objective To study the effect of cyanidin-3-O-glucoside (C3G) on early brain injury (EBI) after subarachnoid hemorrhage (SAH) in adult mice. Methods Seventy-two male C57 mice were randomly divided into 6 groups, including sham operation group, SAH group, vehicle group, low-dose C3G group (10 mg/kg), medium-dose C3G group (20 mg/kg), and high-dose C3G group (30 mg/kg), with 12 mice in each. Twenty-four hours after SAH, the neurological function was assessed by Garcia score and balance beam score. The content of reactive oxygen species (ROS) and malondialdehyde (MDA) in the peripheral blood were detected and then the whole brain tissue was separated for the detection of SAH grade and brain water content in 6 mice of each group. The ratio of GSH/GSSG in the peripheral blood was detected and then the brain tissues were separated for detection of the expression of PKA, p-PKA, CREB, p-CREB and GCLC in the other 6 mice of each group. Results Compared with the sham operation group, the Garcia and balance bean scores and the ratio of GSH/GSSG significantly decreased, and the content of brain water, the SAH grade, the contents of ROS and MDA in the peripheral blood and the expression levels of -PKA and p-CREB and GCLC significantly increased in SAH group (P<0.05). C3G significantly increased the Garcia and balance bean scores and the ratio of GSH/GSSG, and significantly decreased the SAH grade, the brain water content, the contents of ROS and MDA in the peripheral blood and the expression levels of p-PKA, p-CREB and GCLC in adult mice after SAH. Conclusions C3G can improve the EBI in adult mice after SAH, which may be related to the inhibition of PKA/CREB signaling and down-regulation of GCLC expression, and subsequent inhibition of oxidative stress damage.