[關(guān)鍵詞]
[摘要]
目的 利用斑馬魚模型評價異甘草酸鎂注射液、甘草酸二銨注射液、復(fù)方甘草酸苷片、甘草酸二銨腸溶膠囊和注射用復(fù)方甘草酸單銨S 5種甘草酸類藥物制劑的心臟保護作用。方法 利用正常發(fā)育至受精后48 h的心臟熒光轉(zhuǎn)基因斑馬魚作為實驗動物,將斑馬魚隨機分為對照組、陽性對照組、模型組和不同濃度甘草酸制劑樣品組。在24孔板里分別給予不同濃度樣品、陽性對照藥物和造模藥物,加培養(yǎng)水至2 mL后,置于(28±5)℃恒溫光照培養(yǎng)箱讓胚胎繼續(xù)發(fā)育。24 h后,用培養(yǎng)水清洗斑馬魚,置于熒光倒置顯微鏡下觀察斑馬魚心律變化并拍照。其中抗心律失?;钚缘年栃运帪榈ぜt注射液(9 μL·mL-1),造模藥為特非那定(15 μg·mL-1),統(tǒng)計斑馬魚1 min的心率及靜脈竇和動脈球之間的距離(SV-BA)??剐乃セ钚缘年栃运帪榈馗咝粒?.1 μg·mL-1),造模藥品為阿霉素(60 μmol·L-1),統(tǒng)計斑馬魚1 min的心率、心包面積、心室短軸縮短率、每搏輸出量及射血分數(shù)。結(jié)果 甘草酸二銨腸溶膠囊、注射用復(fù)方甘草酸單銨S及異甘草酸鎂注射液有較好的抗心律失?;钚?,注射用復(fù)方甘草酸單銨S具有較好的抗心衰活性。結(jié)論 5種甘草酸制劑在抗心律失常和抗心衰方面具有不同程度活性,可為開發(fā)甘草酸類藥物在心臟保護方面的適應(yīng)癥提供理論依據(jù)。
[Key word]
[Abstract]
Objective To evaluate the cardioprotective effects of five glycyrrhizic acid drugs: Magnesium Isoglycyrrhizinate Injection, Diammonium Glycyrrhizinate Injection, Compound Glycyrrhizin Tablets, Diammonium Glycyrrhizinate Enteric-coated Capsules and Compound Monoammonium Glycyrrhizinate S for Injection using zebrafish model. Methods Zebrafish with fluorescent transgenic heart from normal development to 48 h after fertilization were randomly divided into blank group, positive control group, model group and glycyrrhizic acid preparation sample group with different concentrations. Samples of different concentrations, positive control drugs and modeling drugs were given in 24-well plates, and 2 mL of culture water was added, then the embryos were placed in a (28 ±5)℃ constant temperature light incubator for continued development. After 24 h, zebrafish were cleaned with culture water and placed under inverted fluorescence microscope to observe the change of heart rate. Among them, Danhong Injection (9 μL·mL-1) was the positive drug for antiarrhythmic activity, and terfenadine (15 μg·mL-1) was the modeling drug. The heart rate of Zebrafish within 1 min and the distance between Sinus vena and bulb arterial (SV-BA) were analyzed statistically. The control drug for anti-heart failure activity was digoxin (0.1 μg·mL-1), and the modeling drug was doxorubicin (60 μmol·L-1). The heart rate, pericardial area, ventricular brachyaxis shortening rate, stroke output and ejection fraction of zebrafish within 1 min were statistically analyzed. Results Under the experimental conditions, Diammonium Glycyrrhizinate Enterocapsule Capsule, Compound Monoammonium Glycyrrhizinate S for Injection and Magnesium Isoglycyrrhizinate Injection have better antiarrhythmia activity, and compound monoammonium glycyrrhizinate S for injection has better anti-heart failure activity. Conclusion These five glycyrrhizic acid drugs have different activities in anti-arrhythmia and anti-heart failure. This study can provide theoretical basis for developing the indications of these drugs in cardiac protection.
[中圖分類號]
R285
[基金項目]
江蘇省中藥骨干人才高級研修項目(蘇中醫(yī)科教[2022]17號);宿遷市科技計劃資助項目(K202203);徐州醫(yī)科大學(xué)附屬醫(yī)院發(fā)展基金項目(XYFY202237)