首页|基于风水水肿大鼠模型的麻黄拆分组分的升降浮沉药性研究

基于风水水肿大鼠模型的麻黄拆分组分的升降浮沉药性研究

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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;肺组织细胞的凋亡率及ROS水平显著降低(P<0.01),作用效果为生物碱组分>多糖组分>非生物碱组分.(2)泌尿系统实验结果:与模型组比较,麻黄组、生物碱组、多糖组及通宣理肺丸组大鼠的足趾汗腺着色点数显著增多(P<0.05,P<0.01),麻黄组、生物碱组及通宣理肺丸组大鼠的排尿量显著增加(P<0.01);各给药组大鼠的血清CRE水平无明显变化(P>0.05),尿液中UP水平显著降低(P<0.05,P<0.01),麻黄组、生物碱组、多糖组及通宣理肺丸组大鼠的血清BUN水平及尿液MAU水平显著降低(P<0.05,P<0.01).(3)中枢系统实验结果:与模型组比较,各给药组大鼠的自主活动次数显著增加(P<0.01),麻黄组、生物碱组及通宣理肺丸组大鼠的睡眠时间显著缩短(P<0.05,P<0.01);麻黄组、生物碱组、多糖组及通宣理肺丸组大鼠的活动总距离显著延长(P<0.05,P<0.01).生物碱组分的改善效果最为明显且接近麻黄,提示麻黄生物碱组分的药性偏升浮.(4)消化系统实验结果:与模型组比较,麻黄多糖组大鼠的胃残留率显著降低(P<0.01),小肠推进率及血浆GT水平显著升高(P<0.01);非生物碱组大鼠的血浆SST水平明显升高(P<0.05).结果提示,麻黄多糖组分的药性偏沉降.(5)循环系统实验结果:与模型组比较,给药组大鼠的血清NO水平明显升高(P<0.05,P<0.01),生物碱组大鼠的心脏LVFS明显升高(P<0.05).结论 麻黄生物碱组分表现出升提趋上、轻浮宣散之势,药性偏"升浮",多糖组分表现出趋下之势,药性偏"沉降",可能是麻黄发挥"宣发肺气、发汗解表、利水消肿"功效的物质基础.
Study on the Medicinal Properties of Ascending and Descending,Floating and Sinking on Split Fractions of Ephedrae Herba Based on Wind Edema Rat Model
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),interferon γ(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 staining was used to observe the relevant histopathological changes.Results(1)Results of respiratory system experiments:compared with the model group,the cough latency of rats in each administration group was significantly prolonged(P<0.01),and the times of coughs was significantly reduced(P<0.05,P<0.01),of which the alkaloid and polysaccharide fractions were close to the effect of Ephedrae Herba;the swelling of alveolar walls was reduced,the phenomenon of infiltration of inflammatory cells and epithelial cell detachment in alveoli was alleviated,and the pathological scores were significantly reduced(P<0.05,P<0.01),of which the alkaloid fraction had the most significant improvement effect;the levels of IL-4 and IgE in BALF were significantly reduced(P<0.05,P<0.01),and the level of IFN-γ was significantly increased(P<0.05,P<0.01),of which the alkaloid fraction had the closest improvement effect to that of Ephedrae Herba;and the apoptosis rate of the cells of the lung tissues and the level of ROS were significantly reduced(P<0.01),and the effect was alkaloid fraction>polysaccharide fraction>non-alkaloid fraction.(2)Results of urinary system experiments:compared with the model group,the number of colouring points of the toe sweat glands of rats in the Ephedrae Herba group,alkaloid group,polysaccharide group and Tongxuan Lifei Pills group were significantly increased(P<0.05,P<0.01),and the urinary output of rats in the Ephedrae Herba,alkaloid and Tongxuan Lifei Pills group were significantly increased(P<0.01);there was no significant change in the level of serum CRE in rats of each administration group(P>0.05),and the UP level in urine was significantly reduced(P<0.05,P<0.01),and serum BUN level and MAU level in urine were significantly reduced in rats of the Ephedrae Herba group,alkaloid group,polysaccharide group and Tongxuan Lifei Pills group(P<0.05,P<0.01).(3)Results of central system experiments:compared with the model group,the number of voluntary activities of rats in each administration group was significantly increased(P<0.01),and the sleep time of rats in the Ephedrae Herba group,alkaloid group and Tongxuan Lifei Pills group was significantly shortened(P<0.05,P<0.01);and the total distance of the activities of rats in the Ephedrae Herba,alkaloid,polysaccharide and Tongxuan Lifei Pills groups were significantly lengthened(P<0.05,P<0.01).The improvement effect of alkaloid component was the most obvious and close to that of Ephedrae Herba,suggesting that the medicinal properties of the component of Ephedrae Herba alkaloid were on the ascending and floating side.(4)Results of digestive system experiments:compared with the model group,the gastric residual rate of rats in the Ephedrae Herba polysaccharide group was significantly decreased(P<0.01),and the propulsion rate of the small intestine and the plasma GT level were significantly increased(P<0.01);and the plasma SST level of rats in the non-alkaloid group was significantly increased(P<0.05).The results suggested that the medicinal properties of Ephedrae Herba polysaccharide fractions were tend to be descending and sinking.(5)Results of circulatory system experiments:compared with the model group,the serum NO level of rats in the administered groups was significantly increased(P<0.05,P<0.01),and the cardiac LVFS of rats in the alkaloid group was significantly increased(P<0.05).Conclusion The alkaloid fraction of Ephedrae Herba shows a tendency to rise and float upward,with a tendency to ascending and floating,and the polysaccharide fraction shows a tendency to descending,with a tendency to sink downward,which may be the material basis for the efficacy of Ephedrae Herba in promoting lung qi,inducing sweating to release the exterior,and inducing diuresis to relieve edema.

medicinal propertiesascending and descending,floating and sinkingwind edemaEphedrae Herbaalkaloidpolysaccharideinducing sweating to release the exteriorinducing diuresis to relieve edemarats

张宇涵、徐瑞齐、曾梦楠、吴媛媛、叶珊、李本科、曹兵、冯卫生、夏永刚、郑晓珂

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河南中医药大学,河南 郑州 450046

河南省中药开发工程技术研究中心,河南 郑州 450046

黑龙江中医药大学,黑龙江 哈尔滨 150040

中药药性 升降浮沉 风水水肿 麻黄 生物碱 多糖 发汗解表 利水消肿 大鼠

国家重点研发计划中医药现代化研究专项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

2019YFC1708802ZYQR201810080

2024

中药新药与临床药理
广州中医药大学

中药新药与临床药理

CSTPCD北大核心
影响因子:0.908
ISSN:1003-9783
年,卷(期):2024.35(1)
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