姜黄素通过调节Bcl-2/Bax/Caspase-3信号通路活性保护脑出血大鼠神经细胞的实验研究  

Curcumin Protects Neuron in Rats with Intracerebral Hemorrhage by Regulating the Activity of Bcl-2/Bax/Caspase-3 Signaling Pathway

作　　者：潘飞豹 柯莉 蒋丝丽 蒋世杰[1] PAN Feibao;KE li;JIANG Sili;JIANG Shijie(Suining Central Hospital,Suining 629000,Sichuan,China)

机构地区：[1]遂宁市中心医院,四川遂宁629000

出　　处：《中西医结合心脑血管病杂志》2021年第22期3897-3902,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的探讨姜黄素保护脑出血大鼠神经细胞凋亡的效应及相关信号通路。方法采用血肿裂解液诱导的原代皮层神经元细胞损伤模型进行体外实验,利用不同浓度血肿裂解液对细胞进行不同时间干预后检测神经细胞存活率。将30只大鼠随机分为假手术组(Sham组)、脑出血+溶媒组(CH+V组)、脑出血+姜黄素组(CH+Cur组),采用胶原酶尾状核注射法制备大鼠脑出血模型。Sham组及CH+V组予以等量生理盐水灌胃,CH+Cur组予以姜黄素100 mg/g灌胃,术后2 h、24 h、48 h各注射1次。比较各组大鼠脑含水量、脑组织中氧化应激指标及Bcl-2/Bax/Caspase信号通路相关蛋白表达水平。结果①大脑皮层神经元经0.100溶血产物处理24 h后,细胞存活率明显下降,乳酸脱氢酶水平和细胞凋亡率明显增加,而经姜黄素处理后可有效减弱这一效应。②脑出血后72 h时,与Sham组相比,脑出血大鼠同侧皮层脑组织含水量增加,姜黄素可明显降低脑出血后72 h脑含水量。③与Sham组相比,脑出血大鼠脑组织活性氧(ROS)、8-羟色胺(8-OHDG)、3-硝基酪氨酸、丙二醛(MDA)水平明显升高(P<0.05),而姜黄素干预可明显降低脑出血后72 h ROS、8-OHDG、3-硝基酪氨酸、MDA水平。与Sham组相比,CH+V组谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)活性降低,姜黄素减轻了GSH-Px和SOD的下降。与Sham组相比,脑出血后Kelch样环氧氯丙烷相关蛋白-1(Keap1)表达降低,核因子E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)表达增加;与CH+V组相比,CH+Cur组Keap1、Nrf2和HO-1的表达明显增加。④与CH+V组相比,CH+Cur组Bcl-2表达明显增加;与Sham组比较,CH+V组Bax、活化Caspase-9和活化Caspase-3水平明显升高;与CH+V组比较,CH+Cur组Bax、活化Caspase-9和活化Caspase-3的表达明显降低。⑤与Sham组比较,脑出血诱导的Caspase-3和TUNEL阳性神经元数量明显增加,姜黄素干预后能明显减少活化Caspase-3和TUNEL阳性神�Objective To investigate the protective effect of curcumin(Cur)on neuronal apoptosis in rats with intracerebral hemorrhage.Methods The injury model of primary cortical neurons induced by hematoma lysate(HL)was used in vitro experiments.Thirty rats were randomly divided into sham group,CH+V group,and CH+Cur group.The rat cerebral hemorrhage model was made with collagenase,which was infused into the caudate nucleus.The rats in sham group and CH+V group were given the same amount of normal saline.The rats in CH+Cur group were given curcumin 100 mg/g by gavage.Collagenase was injected within 2,24,48 hours after operation.The brain water content,oxidative stress index,and Bcl-2/Bax/Caspase signaling pathway related protein expression in brain tissues were compared between different groups.Results Compared with sham group,the survival rate of neurons decreased and lactate dehydrogenase(LDH)level and apoptosis rate increased after 24 hours of 0.100 hemolysate(HL)treatment,while curcumin treatment could weaken this effect effectively.At 72 hours after intracerebral hemorrhage,compared with sham group,the water content of ipsilateral cortex of rats increased,and curcumin could reduce the increase of brain water content.Compared with sham group,the levels of reactive oxygen species(ROS),8-hydroxy-2′-deoxyguanosine(8-OHdG),3-nitrotyrosine(3-NT),and malondialdehyde(MDA)in brain tissue of rats increased significantly(P<0.05),while curcumin can reduce the levels of each index significantly.The activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)decreased in CH+V group,while curcumin alleviated the decrease of GSH-Px and SOD.Compared with sham group,Kelch-like epichlorohydrin-associated protein 1(Keap1)expression decreased,nuclear factor erythtoid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)expression increased after intracerebral hemorrhage.Compared with CH+V group,the expressions of Keap1,Nrf2,and HO-1 increased significantly in CH+Cur group.Compared with CH+V group,the expression of Bcl-2 in CH+C

关 键 词：脑出血 姜黄素 神经细胞凋亡 氧化应激 实验研究 

分 类 号：R74[医药卫生—神经病学与精神病学]