| 摘要: |
| 目的探讨富氢盐水对蛛网膜下腔出血（SAH）大鼠神经保护作用的机制。方法将69只SD大鼠随机分为假手术组、0.9%氯化钠溶液（生理盐水）组、富氢盐水组，采用血管内穿刺法建立SAH模型（假手术组除了最后不刺破大脑前动脉与大脑中动脉分叉外，其余过程与SAH造模相同），剔除造模后死亡或SAH评分＜8分的15只，最终每组各18只。生理盐水组、富氢盐水组均在造模后立即腹腔注射等量的0.9%氯化钠溶液、富氢盐水，8h后再注射1次。造模后24h，评估并比较3组大鼠死亡率、神经功能评分、SAH评分、脑组织含水量、凋亡神经细胞计数以及活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）及谷胱甘肽过氧化物酶（GSH-Px）水平，以及磷酸化的JAK2（pJAK2）、总JAK2（tJAK2）、Bax、Caspase-3蛋白表达水平。结果SAH发生后24h，蛛网膜下腔血凝块主要分布在Willis环和脑干腹侧周围。3组大鼠死亡率、SAH评分比较，差异均无统计学意义（均P＞0.05）。与假手术组比较，生理盐水组神经功能评分、SOD、GSH-Px水平均明显降低（P＜0.05）；与生理盐水组比较，富氢盐水组均明显升高（P＜0.05）。与假手术组比较，生理盐水组脑组织含水量、ROS、MDA水平均明显升高（P＜0.05）；与生理盐水组比较，富氢盐水组均明显降低（P＜0.05）。假手术组几乎没有发现凋亡神经细胞；与假手术组比较，生理盐水组凋亡神经细胞计数明显增加；与生理盐水组比较，富氢盐水组凋亡神经细胞计数明显减少。与假手术组比较，生理盐水组、富氢盐水组pJAK2/tJAK2、Bax、Caspase-3蛋白表达水平均较高（P＜0.05）；与生理盐水组比较，富氢盐水组明显降低（P＜0.05）。结论富氢盐水可以减轻SAH后的早期脑损伤，改善SAH后的神经功能损伤，其作用机制部分通过抑制JAK2的激活实现。 |
| 关键词: 富氢盐水 蛛网膜下腔出血 神经功能 作用机制 |
| DOI：10.12056/j.issn.1006-2785.2017.40.8.2018-241 |
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| Neuroprotective effect and mechanism of hydrogen-rich saline against subarachnoid hemorrhage in rats |
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the First Affiliated Hospital，Zhejiang University School of Medicine
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| Abstract: |
| Objective To investigate the neuroprotective effect and mechanism of hydrogen-rich saline (HS) injection against subarachnoid hemorrhage (SAH) in rats. Methods SD rats were randomly divided into Sham, SAH + vehicle (0.9% saline), and SAH+HS groups with 18 rats in each group. SAH was induced with endovascular perforation method, HS or an equal volume of vehicle was injected intraperitoneally immediately after operation and repeated 8h later. Sham-operated rats underwent identical procedures except no perforation was performed. Mortality, SAH grade, neurological score, brain water content, cell apoptosis, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), the protein expression of tJAK2, pJAK2, Bax and Caspase-3 were evaluated at 24h after operation. Results At 24h after SAH, subarachnoid blood clots were mainly found around the circle of Willis and ventral brainstem. No
significant differences were observed in mortality and SAH score among groups (P ＞0.05) . The neurologic function and activities
of SOD and GSH-Px were decreased in SAH+vehicle group compared to Sham group, while increased significantly in SAH+HS group compared to vehicle group. The brain water content and levels of ROS and MDA were increased in vehicle group compared to Sham group, while decreased in HS group compared to vehicle. There was almost no TUNEL-positive apoptotic neurons were detected in the sham group. In the SAH + vehicle group, the apoptotic cells increased markedly compared with the sham group, and mainly colocalized with neurons. However, compared with the SAH + vehicle group, HS reduced the number of apoptotic cells. The protein levels of pJAK2, Bax and cleaved caspase 3 were up-regulated after SAH. However, HS injection reversed the changes above protein levels. Conclusion The results show that hydrogen-rich saline can attenuate neuronal apoptosis in early brain injury and improve the neurological function in rats with subarachnoid hemorrahage, which may be asso- ciated with the inhibition of JAK2 activation. |
| Key words: Hydrogen-rich saline Subarachnoid hemorrhage Neurologic function Mechanism |
