机构地区:[1]河南中医药大学,河南郑州450046 [2]河南省中药开发工程技术研究中心,河南郑州450046 [3]黑龙江中医药大学,黑龙江哈尔滨150040
出 处:《中药新药与临床药理》2024年第1期65-76,共12页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:国家重点研发计划-中医药现代化研究专项(2019YFC1708802);河南省高层次人才特殊支持计划“中原千人计划”-中原领军人才项目(ZYQR201810080)。
摘 要:目的基于风水水肿大鼠模型探讨麻黄拆分组分(生物碱、非生物碱、多糖)的升降浮沉药性物质基础。方法将70只SD大鼠随机分为正常组、模型组、生物碱组(51.48 mg·kg^(-1))、非生物碱组(215.28 mg·kg^(-1))、多糖组(276.12 mg·kg^(-1))、麻黄组(麻黄水煎液4670 mg·kg^(-1))及通宣理肺丸组(阳性药组,4326 mg·kg^(-1))。采用尾静脉注射阿霉素结合吹风刺激的方式建立风水水肿大鼠模型,以大鼠出现四肢浮肿、恶风、弓背、毛松、喷嚏、流涕、小便减少等症状为造模成功。采用灌胃给药(10 mL·kg^(-1)),每日1次,连续给药21 d。通过氨水诱咳实验观察大鼠咳嗽状况;测定大鼠汗腺分泌功能、自主活动次数、睡眠时间;通过旷场实验评估大鼠自主活动情况;采用小动物超声心动仪检测大鼠的心功能指标:心率(HR)、心输出量(CO)、左心室射血分数(LVEF)及左心室短轴缩短率(LVFS);检测大鼠胃残留率、小肠推进率;测定心、肝、脾、肺、肾各脏器系数;生化指标检测:尿液中的尿蛋白(UP)、尿微量白蛋白(MAU)水平,支气管肺泡灌洗液(BALF)中的白细胞介素4(IL-4)、γ干扰素(IFN-γ)、免疫球蛋白E(IgE)水平,血清中的肌酐(CER)、尿素氮(BUN)、一氧化氮(NO)水平,血浆中胃动素(MTL)、胃泌素(GT)、生长抑素(SST)水平;采用流式细胞术检测肺组织细胞凋亡及其活性氧(ROS)水平;HE染色法观察相关组织病理变化。结果(1)呼吸系统实验结果:与模型组比较,各给药组大鼠的咳嗽潜伏期显著延长(P<0.01),咳嗽次数显著减少(P<0.05,P<0.01),其中生物碱和多糖组分的效果接近麻黄;肺泡壁肿胀减轻,肺泡内炎症细胞浸润及上皮细胞脱落现象有所缓解,病理评分显著降低(P<0.05,P<0.01),其中生物碱组分改善效果最为显著;BALF中的IL-4、IgE水平显著降低(P<0.05,P<0.01),IFN-γ的水平显著升高(P<0.05,P<0.01),其中生物碱组分的改善效果最接近麻黄;肺组织细胞Objective To explore the medicinal properties of ascending and descending,floating and sinking on split fractions of Ephedrae Herba(alkaloids,non-alkaloids and polysaccharides)based on the rat model of wind edema.Method Seventy SD rats were randomly divided into normal group,model group,alkaloid group(51.48 mg·kg^(-1)),non-alkaloid group(215.28 mg·kg^(-1)),polysaccharide group(276.12 mg·kg^(-1)),Ephedrae Herba group(Ephedrae Herba decoction 4670 mg·kg^(-1)),and Tongxuan Lifei Pills group(positive drug group,4326 mg·kg^(-1)).The rat model of wind edema was established by tail vein injection of Adriamycin combined with wind-blowing stimulation,and the modelling was considered successful by the appearance of symptoms such as oedema of the limbs,aversion to wind,arched back,loose hair,sneezing,runny nose,and reduced urination in the rats.The drug was administered by gavage(10 mL·kg^(-1))once a day for 21 consecutive days.The coughing condition of the rats was observed by ammonia-induced cough test;the secretion function of sweat glands,the number of voluntary activities,and the sleeping time of the rats were measured;the voluntary activities of the rats were evaluated by open field test;and the cardiac function indexes of the rats were examined by echocardiography for heart rate(HR),cardiac output(CO),left ventricular ejection fraction(LVEF),and left ventricular fraction shortening(LVFS);gastric residual rate and small intestinal propulsion rate of rats were detected;the coefficients of heart,liver,spleen,lungs and kidneys were measured;biochemical indexes were detected:urinary protein(UP)and microalbuminuria(MAU)levels in urine,interleukin 4(IL-4),interferonγ(IFN-γ)and immunoglobulin E(IgE)levels in bronchoalveolar lavage fluid(BALF),creatinine(CER),urea nitrogen(BUN)and nitric oxide(NO)levels in serum;gastric motility factor(MTL),gastrin(GT)and growth inhibitor(SST)levels in plasma were detected;flow cytometry was used to detect apoptosis of lung tissue cells and their reactive oxygen species(ROS)levels;HE
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