穿心莲内酯对大鼠缺血性脑损伤及核因子E2相关因子2/血红素加氧酶1通路的影响  

Effects of andrographolide on ischemic brain injury and nuclear factor E2 related factor 2/heme oxygenase 1 pathway in rats

作　　者：王旭东[1] 朱海生[1] 李晓蕾[1] 樊丽敏 Wang Xudong;Zhu Haisheng;Li Xiaolei;Fan Limin(Department of Neurology,Handan Central Hospital,Handan 056000,China;Department of Function,Handan Second Hospital,Handan 056000,China)

机构地区：[1]河北省邯郸市中心医院神经内三科,056000 [2]河北省邯郸市第二医院功能科,056000

出　　处：《心脑血管病防治》2023年第5期17-22,共6页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：河北省医学科学研究课题(20191836)。

摘　　要：目的探讨穿心莲内酯(AND)对缺血性脑损伤(IBI)的影响及其作用机制。方法将192只健康SD大鼠随机分为假手术组(Sham组),模型组(IBI组),低、中、高剂量AND组和尼莫地平(NMP)组,每组32只;采用线圈阻断大脑中动脉的方法制备IBI大鼠模型,造模完成后,低、中、高剂量AND组分别给予25 mg/kg、50 mg/kg、100 mg/kg的AND溶液灌胃,NMP组以10 mg/kg的NMP溶液灌胃,Sham组和IBI组给予生理盐水5 mL/kg灌胃,疗程7 d。采用Longa评分标准进行神经功能缺损评分;测定脑梗死率、脑含水量、观察梗死灶周边2 mm区域半暗带神经细胞凋亡状况、丙二醛(MDA)含量和抗氧化酶活性,检测炎症因子含量、核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、核因子-κB(NF-κB)、半胱氨酸蛋白酶-3(Caspase-3)、B淋巴细胞瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达。结果与Sham组相比,IBI组神经功能缺失评分、脑梗死率、脑含水量均显著升高(均P<0.05);梗死灶周边2 mm区域半暗带凋亡细胞数量明显增多,凋亡指数显著升高(P<0.05);MDA含量显著升高、超氧化物歧化酶和谷胱甘肽过氧化物酶活性显著降低(均P<0.05),肿瘤坏死因子-α、白细胞介素-1β、干扰素-γ含量显著升高(均P<0.05),Nrf2、HO-1、Bcl-2表达量显著降低而NF-κB、Caspase-3、Bax表达量显著升高(均P<0.05)。AND各组上述作用呈现一定的剂量依赖性,高剂量AND组作用最强,且高剂量AND组对各指标的作用优于NMP组(P<0.05)。结论AND对大鼠IBI具有保护作用,其机制可能与激活Nrf2/HO-1通路,进而抑制氧化应激、炎症反应和神经细胞凋亡有关。Objective To investigate the effect of andrographolide(AND)on ischemic brain injury(IBI)and its mechanism.Methods A total of 192 healthy SD rats were randomly divided into sham operation group(Sham group),model group(IBI group),low,medium,high dose AND groups and nimodipine(NMP)group,with 32 rats in each group.Rat models with IBI were prepared via blocking middle cerebral artery by coil.Twenty-five mg/kg,50 mg/kg,100 mg/kg AND solutions were given by gavage respectively in the low-,medium-and high-dose AND groups;10 mg/kg NMP solution was given in NMP group,and 5 mL/kg saline was given in Sham and IBI group,respectively.All groups were treated for 7 days.Neurological deficit score was calculated according to the Longa scoring standard.Cerebral infarction rate and cerebral water content was detected.Neuron apoptosis in the 2 mm area in penumbra around infarct,malondialdehyde(MDA)content and antioxidant enzyme activity were observed.Content of inflammatory factors and expression of nuclear factor E2 related factor 2(Nrf2),heme oxygenase 1(HO-1),nuclear factor-κB(NF-κB),Caspase-3,B cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax)were detected.Results Compared with Sham group,neurological deficit score,cerebral infarction rate and cerebral water content in IBI group increased significantly(all P<0.05).The number of apoptotic cells in the 2 mm area in penumbra around infarct and the apoptotic index significantly increased(P<0.05).MDA content significantly increased;the activities of superoxide dismutase and glutathione peroxidase significantly reduced(all P<0.05).The contents of tumor necrosis factor-α,interleukin-1β,interferon-γsignificantly increased(all P<0.05).The expression of Nrf2,HO-1,Bcl-2 significantly decreased,while the expression of NF-κB,Caspase-3 and Bax significantly increased(all P<0.05).The above effects in AND groups were dose-dependent.High-dose AND group had the strongest effect and better effects on each index than that of the NMP group(P<0.05).Conclusion AND has protective effect on IBI

关 键 词：穿心莲内酯 脑缺血 炎症 氧化应激 凋亡 核因子E2相关因子2/血红素加氧酶1通路 

分 类 号：R285.5[医药卫生—中药学]