基于TGF-β1/Smad3 信号通路探讨三七皂苷对脑血栓的治疗作用OA
Exploring the Therapeutic Effect of Panax Notoginseng Saponins on Cerebral Thrombosis Based on the TGF-β1/Smad3 Signaling Pathway
目的:探讨三七皂苷通过TGF-β1/Smad3 通路对脑血栓的治疗作用.方法:建立大脑中动脉闭塞(MCAO)大鼠模型,60 只SD大鼠随机分为6 组,分别为空白组、模型组、脑心通胶囊组(432 mg/kg)、阿托伐他汀组(1.8 mg/kg)、三七皂苷低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高剂量组(100 mg/kg).另取10 只假手术组.各组连续灌胃给药4 周,空白组给予生理盐水.进行旷场实验和水迷宫实验,通过检测大鼠的线性度、平均速度、潜伏期等指标来检测大鼠的神经损伤;采用激光多普勒血流仪检测脑组织局部血流量;Elisa法检测血清中组织型纤溶酶原激活物(T-pa)、纤溶酶原激活物抑制剂-1(Pai-1)含量,SPR法进行转化生长因子-β1(TGF-β1)与三七皂苷的亲和力实验,TTC染色测定脑梗死体积占比、IHC与RT-qPCR技术,分别从蛋白定位、基因转录水平检测脑组织TGF-β1 的表达差异.结果:行为学结果显示,与模型组比较,三七皂苷组大鼠均速度、活动次数、休息时间和线性度等指标显著改善(P<0.05);三七皂苷组大鼠血清 T-pa 水平极显著性降低、Pai-1 水平升高(P<0.01);三七皂苷高剂量组大鼠脑组织中 TGF-β1 mRNA 表达极显著性降低(P<0.01);各剂量三七皂苷组大鼠脑组织中 TGF-β1 蛋白表达均极显著性降低(P<0.01).结论:三七皂苷可改善脑梗死大鼠神经功能,通过调节T-pa/Pai-1 水平,抑制TGF-β1 表达治疗脑血栓.
Objective:To investigate the therapeutic effect of notoginsenoside on cerebral thrombosis through TGF-β1/Smad3 pathway.Methods:A rat model of middle cerebral artery occlusion(MCAO)was established.A total of 60 SD rats were randomly divided into six groups:blank group,model group,Naoxintong Capsule group(432 mg/kg),atorvastatin group(1.8 mg/kg),and low-dose(25 mg/kg),medium-dose(50 mg/kg)and high-dose(100 mg/kg)Panax notoginseng saponins groups.Another 10 rats were assigned to the sham operation group.Rats in each group were given intragastric administration for 4 consecutive weeks,and the blank group was given normal saline.Open field test and Morris water maze test were performed to evaluate neurological injury by detecting indicators including linearity,average speed and incubation period.Laser Doppler flowmetry was used to determine local cerebral blood flow.The serum levels of tissue-type plasminogen activator(t-PA)and plasminogen activator inhibitor-1(PAI-1)were measured by ELISA.Surface plasmon resonance(SPR)assay was adopted to detect the binding affinity between transforming growth factor-β1(TGF-β1)and Panax notoginseng saponins.TTC staining was used to calculate the percentage of cerebral infarction volume.Immunohistochemistry(IHC)and RT-qPCR were applied to detect the differential expression of TGF-β1 in brain tissue at protein localization and gene transcription levels,respectively.Results:Behavioral results showed that compared with the model group,behavioral indexes such as average speed,activity frequency,rest time and linearity were significantly improved in Panax notoginseng saponins groups(P<0.05).The serum level of t-PA was extremely significantly decreased,while PAI-1 level was increased in Panax notoginseng saponins groups(P<0.01).The mRNA expression of TGF-β1 in brain tissue was extremely significantly down-regulated in the high-dose Panax notoginseng saponins group(P<0.01).The protein expression of TGF-β1 in brain tissue was extremely significantly reduced in all dose groups of Panax notoginseng saponins(P<0.01).Conclusion:Panax notoginseng saponins can improve neurological function in rats with cerebral infarction,and treat cerebral thrombosis by regulating the levels of t-PA/PAI-1 and inhibiting the expression of TGF-β1.
葛学林;蒙艳丽;许庆瑞;王冬;薛岩;董羽佳;常艳宾;尹俪桥;张海峰;梁爽;王伟明
黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036哈尔滨市龙生北药生物工程股份有限公司·黑龙江 哈尔滨 150036哈尔滨市龙生北药生物工程股份有限公司·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036黑龙江省中医药科学院·黑龙江 哈尔滨 150036
脑血栓三七皂苷转化生长因子-β1组织型纤溶酶原激活剂纤溶酶原激活剂抑制剂-1
Panax Notoginseng Saponinscerebral thrombosisTGF-β1t-PaPAI-1
《中国中医药科技》 2026 (3)
233-240,8
国家中药材产业技术体系专项项目(CARS-21)2023 年全国中药特色技术传承人才培训项目(T20234832005)黑龙江省自然科学基金项目(LH2023H076)
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