摘要
目的:观察通窍活血汤对蛛网膜下腔出血(SAH)大鼠的神经保护作用,并探讨其作用机制。方法:将60只SD大鼠随机分为假手术组,模型组,通窍活血汤低、中、高(3、6、12 g/kg)剂量组各12只。采用改良二次枕大池注血法制作SAH大鼠模型。造模成功后,通窍活血汤低、中、高剂量组大鼠分别灌胃对应剂量的通窍活血汤溶液治疗,假手术组和模型组大鼠灌胃等量的0.9%氯化钠溶液,连续灌胃7 d。于治疗第1、3、5、7天评估各组大鼠Bederson神经功能评分;每组各取6只大鼠,在治疗第3、7天分批取材,采用酶联免疫吸附法检测各组大鼠海马组织肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平;免疫组织化学法测定各组大鼠醌氧化还原酶1(NQO-1)、核因子E2相关因子2(Nrf2)蛋白表达。结果:与假手术组比较,模型组大鼠在治疗第1、3、5、7天的Bederson神经功能评分均升高(P<0.05);通窍活血汤中、高剂量组大鼠在治疗第5、7天的Bederson神经功能评分均较模型组降低(P<0.05)。与假手术组比较,模型组大鼠治疗第3、7天海马组织中TNF-α、IL-1β含量明显升高(P<0.01),海马齿状回区NQO-1、Nrf2蛋白表达明显降低(P<0.01);与模型组比较,通窍活血汤低、中、高剂量组大鼠治疗第3、7天海马组织中TNF-α、IL-1β含量降低(P<0.01),通窍活血汤低、中、高剂量组大鼠海马齿状回区NQO-1、Nrf2蛋白表达升高(P<0.05)。结论:通窍活血汤可通过抗氧化应激,减轻炎性反应来改善SAH大鼠神经功能,其机制与调节Nrf2-抗氧化反应元件(Nrf2-ARE)信号通路下游NQO-1、Nrf2蛋白水平有关。
Objective:To observe the neuroprotective effect of Tongqiao Huoxue Decoction on rats with subarachnoid hemorrhage(SAH)and to discuss its mechanism.Methods:A total of 60 SD rats were randomly divided into the sham-operation group,the model group,the low-dose,medium-dose and high-dose of Tongqiao Huoxue Decoction group(3,6 and 12 g/kg),with 12 rats in each group.The SAH rat models were established by modified secondary blood injection into occipital cistern.After successful modeling,rats in the low-dose,medium-dose and high-dose of Tongqiao Huoxue Decoction groups were treated with Tongqiao Huoxue Decoction solution of corresponding dose respectively,and rats in the sham-operation group and the model group were treated with 0.9%sodium chloride solution of the same amount by gavage for consecutive day.The Bederson neurological function scores of rats in each group were evaluated on the first,third,fifth and seventh day of treatment;six rats in each group were taken in batches on the third and seventh day of treatment,and levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay;the protein expressions of quinone oxidoreductase(NQO-1)and nuclear factor erythroid 2-related factor 2(Nrf2)were determined by immunohistochemistry.Results:Compared with those in the sham-operation group,the Bederson neurological function scores in the model group were higher on the first,third,fifth and seventh day of treatment(P<0.05);the Bederson neurological function scores of rats in the Tongqiao Huoxue Decoction group of of medium-dose and high-dose were decreased when compared with those in the model group on the fifth and seventh day of treatment(P<0.05).Compared with those in the sham-operation group,the levels of TNF-αand IL-1βin the hippocampus of rats in the model group were significantly increased on the third and seventh day of treatment(P<0.01),the protein expressions of NQO-1 and Nrf2 in the hippocampal dentate gyrus were
作者
魏绪旺
朱平
郭志丽
金敏艳
沈斌
孙长忠
刘鹏鹏
高晨琛
WEI Xuwang;ZHU Ping;GUO Zhili;JIN Minyan;SHEN Bin;SUN Changzhong;LIU Pengpeng;GAO Chenchen
出处
《新中医》
CAS
2023年第7期15-20,共6页
New Chinese Medicine
基金
浙江省中医药科技计划项目(2021Z285)
嘉兴市科技计划民生科技创新研究项目(2021AD300222)。
关键词
蛛网膜下腔出血
通窍活血汤
神经功能
核因子E2相关因子2-抗氧化反应元件
信号通路
Subarachnoid hemorrhage
Tongqiao Huoxue Decoction
Neurological function
Nuclear factor erythroid 2-related factor 2 antioxidant responsive element
Signal pathway
