青黛口服起效的关键:胆汁作用的体内外验证  

Key to Indigo Naturalis’oral effectiveness:in vivo and in vitro verification of bile action

作　　者：徐小蓉 冉飞 贺亚男[1] 苟桦梅 慈志敏[1] 王芳 杨明 张定堃[1] 韩丽[1] XU Xiao-rong;RAN Fei;HE Ya-nan;GOU Hua-mei;CI Zhi-min;WANG Fang;YANG Ming;ZHANG Ding-kun;HAN Li(State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,College of Pharmacy,Chengdu University of Traditional Chinese Medicine y Chengdu 611137,China;Key Laboratory of Modern Chinese Medicine Preparation,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Narwhang 330004,China)

机构地区：[1]成都中医药大学药学院西南特色中药资源省部共建国家重点实验室,四川成都611137 [2]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中国中药杂志》2021年第13期3198-3204,共7页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2018YFC1707205);国家自然科学基金面上项目(81773918);成都中医药大学中药学学科特色创新科研团队项目(CXTD2018006)。

摘　　要：青黛主要由10%的有机物和90%的无机物组成,润湿性差,疏水性强,靛蓝、靛玉红等有效成分在水中几乎不溶,口服后如何起效亟待揭示。为此,该文提出“青黛在胃液强酸环境中无机物溶解,在肠液胆汁环境中有机物增溶”的体内起效假说并进行了验证。首先,采用溶出仪模拟青黛在不同消化液中的变化过程,比较低剂量与正常量胆汁对无机物溶解和有机物释放的影响。观察不同消化液中青黛的表面形态与元素变化,研究发现胆汁是促进青黛中有机物和无机物溶出的关键。进一步采用2,4-二硝基苯酚诱导的大鼠发热模型研究青黛对正常大鼠和胆管结扎大鼠的解热作用,发现青黛对正常大鼠的解热作用优于胆管结扎大鼠。上述结果表明,青黛口服后,碳酸钙载体在酸性胃液中转变为微溶状态,少量有机物释放出来,当青黛进入与胆汁混合的肠液时,载体大量溶解,靛蓝、靛玉红等有机物大量溶出,从而吸收入血并发挥疗效。该研究对青黛的临床应用具有一定的指导意义,对于胆汁分泌不足的患者(如胆管切除),口服青黛可能疗效不佳,应予以关注。Indigo Naturalis(IN)is mainly composed of 10%organic matter and 90%inorganic matter,with a poor wettability and strong hydrophobicity.Indigo,indirubin and effective ingredients are almost insoluble in water.And how it exerts its effect after oral administration still needs to be revealed.For this reason,this study put forward the hypothesis that"Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis.First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared.After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN.Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats.It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats.The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released.When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect.This study has a certain significance for guiding clinical application of IN.For patients with insufficient bile secretion(such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

关 键 词：青黛 起效机制 胆汁 解热作用 增溶 

分 类 号：R285.5[医药卫生—中药学]