摘要
目的观察风药(葛根、石菖蒲)与三七总皂苷配伍后对脑缺血再灌注大鼠的神经保护作用, 阐明"风药增效"的作用机制。方法将140只雄性SD大鼠按随机数字表法分为假手术组、模型组、三七总皂苷组、葛根组、石菖蒲组、葛根+三七总皂苷组、石菖蒲+三七总皂苷组, 每组20只。除假手术组外, 其余各组采用改良Longa线栓法建立脑缺血再灌注模型。各组给予相应药物干预7 d后, 采用Zea-longa评分法进行神经功能评分, TTC染色法测定脑梗死体积, 伊文思蓝(EB)染色检测缺血侧脑组织血脑屏障(BBB)通透性, 透射电子显微镜观察BBB超微结构, 免疫组化染色检测脑组织密封蛋白(Claudin 5)表达, Western blot检测闭锁小带蛋白1(ZO-1)、主要促进因子超家族成员2a(Mfsd2a)、闭合蛋白(Occludin)和P糖蛋白(P-gp)、单羧酸转运蛋白1(MCT1)、乳腺癌抗性蛋白(BCRP)表达。结果与模型组比较, 各给药组大鼠神经功能评分降低(P<0.05), 脑梗死率降低(P<0.05), 脑组织EB含量下降(P<0.05), 脑组织Claudin 5、ZO-1、Mfsd2a、Occludin蛋白表达升高(P<0.05), P-gp、BCRP、MCT1蛋白表达降低(P<0.05), 且葛根+三七总皂苷组、石菖蒲+三七总皂苷组Claudin 5、ZO-1、Mfsd2a、Occludin蛋白表达高于各单独用药组(P<0.05), MCT1蛋白表达低于各单独给药组(P<0.05);葛根+三七总皂苷组ZO-1蛋白表达水平高于单独给药组(P<0.05);石菖蒲+三七总皂苷组P-gp蛋白表达低于三七总皂苷组、石菖蒲组及葛根+三七总皂苷组(P<0.05)。结论风药(葛根、石菖蒲)可增强三七总皂苷对脑缺血再灌注大鼠的神经保护作用, 其机制可能与保护BBB结构完整性、维持中枢屏障特性, 同时调节物质转运蛋白、提高药物脑内含量有关。
Objective:To observe the neuroprotective effect of wind medicine(Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma)in combination with Panax ginseng total saponin(PNS)on cerebral ischemia-reperfusion rats;To elucidate the mechanism of"wind medicine increasing effect".Methods:Totally 140 male SD rats were divided into sham-operation group,model group,PNS group,Puerariae Lobatue Radix group,Acori Tatarinowii Rhizoma group,Puerariae Lobatue Radix+PNS group,Acori Tatarinowii Rhizoma+PNS group according to the random number table method,with 20 rats in each group.Except for the sham-operation group,the cerebral ischemia/reperfusion rat model was established using the modified Longa line bolus method in the remaining groups.After 7 d of administration of the appropriate pharmacologic intervention in each group,neurological dysfunction was evaluated by Zea-longa score after final administration,cerebral infarct volume was determined by TTC staining;blood brain barrier(BBB)permeability of brain tissue on the ischemic side was detected by Evans blue content;BBB ultrastructure of each group of rats was observed by transmission electron microscopy;Claudin 5 protein expression level was detected by immunohistochemistry;Zonula occludens-1(ZO-1),major facilitator supeffamily domain-containing protein 2a(Mfsd2a),Occludin,P-glycoprotein(P-gp),Monocarboxylate Transporters-1(MCT1)and breast cancer resistance protein(BCRP)protein expression levels were detected by Western-blot.Results:Compared with the model group,the rat neurological function scores were reduced in each administration group(P<0.05),infarct volume was reduced(P<0.05),EB content of brain tissue decreased(P<0.05),protein expressions of Claudin 5,ZO-1,Mfsd2a and Occludin in brain tissue were elevated(P<0.05),the protein expressions of P-gp,BCRP and MCT1 were reduced(P<0.05),and the protein expressions of Claudin 5,Mfsd2a,and Occludin was higher in the Puerariae Lobatue Radix+PNS group and Acori Tatarinowii Rhizoma+PNS group than that of each group of medication al
作者
郝琳瑶
李双阳
任俊豪
王小强
王凌雪
张德绸
唐红梅
白雪
Hao Linyao;Li Shuangyang;Ren Junhao;Wang Xiaoqiang;Wang Lingxue;Zhang Dechou;Tang Hongmei;Bai Xue(School of Integrative Medicine,Southwest Medical University,Luzhou 646000,China;Department of Neurology,the Afiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000,China;Institute of Integrated Traditional Chinese and Western Medicine,Southwest Medical University,Luzhou 646000,China;Department of Brain Disease,Sichuan Integrated Traditional Chinese and Western Medicine Hospital,Chengdu 610000,China;Traditional Chinese Medicine Phenomics Research Center,Affiliated Traditional Chinese Medicine Hospital,Southwest Medical University,Luzhou 646000,China)
出处
《国际中医中药杂志》
2024年第8期1006-1014,共9页
International Journal of Traditional Chinese Medicine
基金
国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202207)
四川省科技计划(2022YFS0613)
四川省中医药管理局科研项目(2022CP1717,2023MS276)
泸州市科技局重点研发项目(2020-SYF-30)
西南医科大学附属中医医院学科创新团队(2022-CXTD-05)。
关键词
脑缺血
再灌注损伤
血脑屏障
玄府
风药(中药)
三七皂苷
大鼠
Brain ischemia
Reperfusion injury
Blood-brain barrier
Sweatpore
Wind drugs(TCD)
Notoginsenoside
Rats
