摘要
目的:评价龙生蛭胶囊对脑卒中大鼠行为学影响及其对血清生化学和核转录因子-κB(NF-κB)和半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)的影响。方法:采用健康雄性SD大鼠,采用单侧大脑中动脉永久性结扎手术(p MCAO),将模型制备成功大鼠随机分为模型组,尼莫地平组(12 mg·kg^-1),龙生蛭胶囊高、中、低剂量组(2.4,1.2,0.6 g·kg^-1),同时设置假手术组。连续灌胃给药14 d,分别对大鼠神经缺陷功能进行评分并观察期行为学;实验结束,腹主动脉取血,考察血清超氧化物歧化酶(SOD),一氧化氮(NO)和丙二醛(MDA)的变化;解剖取脑组织进行2,3,5-氯化三苯基四氮唑(TTC)染色观察龙生蛭胶囊对脑梗死体积变化,并测定龙生蛭胶囊对脑含水量测定影响;苏木素-伊红(HE)染色观察梗死侧脑组织病理变化;采用蛋白免疫印迹法(Western blot)和免疫组化检测梗死侧脑组织NF-κB和Caspase-3的表达情况。结果:与假手术比较,模型组神经功能评分显著升高(P<0.01),旋转耐受,抓力明显降低(P<0.01),脑含水量及梗死体积显著升高(P<0.01),SOD活力显著降低(P<0.01),NO和MDA含量显著升高(P<0.01),脑组织中NF-κB以及Caspase-3表达显著升高(P<0.01)。与模型组比较,龙生蛭胶囊能够显著降低神经功能缺陷行为学评分(P<0.05);提高大鼠旋转耐受力,大鼠抓力并提高大鼠自主活动能力;与模型组比较,各给药组能够明显降低脑水含量以及脑梗死体积(P<0.05,P<0.01);能够明显提高血清中SOD活性(P<0.01),降低NO和MDA含量(P<0.05)。能够明显降低脑卒中大鼠脑组织病理损伤,抑制NF-κB以及Caspase-3的表达。结论:龙生蛭胶囊能够改善大鼠的神经功能缺陷,提高大鼠的肌力和自主运动能力,其对脑组织的保护作用可能与抗氧化,抑制NF-κB以及Caspase-3的表达有关。
Objective:To investigate the effect of Longshengzhi capsule(LSZC)on behavior,serum biochemical index,nuclear transcription factor-κB(NF-κB)and cysteine aspartate-specific protease-3(Caspase-3)in stroke rats.Method:Ischaemic stroke was induced by the permanent middle cerebral artery occlusion(pMCAO).The male sprague-dawley rats with successful pMCAO modeling were randomly divided into five groups:model(pMCAO)group,nimodipine(12 mg·kg^-1)group and LSZC groups(2.4,1.2,0.6 g·kg^-1).A sham group also set in the study.The intragastric administration lasted for 14 days.The rats were tested for neurological deficits,grip strength,rotation tolerance.An open field test was also performed to evaluate the behavior.The pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride(TTC)staining,and hematoxylin and eosin(HE)staining.In addition,the levels of malondialdehyde(MDA),nitric oxide(NO)and superoxide dismutase(SOD)in rat serum were tested in the experiment.Immunohistochemistry(ICH)and Western blot were used to analyze the expressions of Caspase-3 and NF-κB.Result:Compared the model group,LSZC significantly improved the grip strength,rotation tolerance and spontaneous activity.LSZC markedly reduced infarct volume,water content of brain,neurological scores,body weight decline in MCAO stroke rats(P<0.05,P<0.01).LSZC significantly decreased the levels of NO and MDA,but increased SOD activity(P<0.05,P<0.01).LSZC recovered neuronal morphologic damage in MCAO rats,and down-regulated the expressions of Caspase-3 and NF-κB.Conclusion:LSZC treatment can improve neurological deficit function and protect the brain of stroke rats.This effect may be realized by down-regulating the expressions of NF-κB and Caspase-3.
作者
孙晓丽
王勇
刘俊杰
李春
杨双杰
王旨引
谭楠楠
王伟
SUN Xiao-li;WANG Yong;LIU Jun-jie;LI Chun;YANG Shuang-jie;WANG Zhi-yin;TAN Nan-nan;WANG Wei(Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第24期23-29,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金重点项目(81530100)
国家重点研发计划项目(2017YFC1700100)
