不同晶型丹皮酚的药动学及抗痛经作用研究  

Pharmacokinetics and anti-dysmenorrheal effect of paeonol polymorphs

作　　者：周洪亮 王海丹 王泽琨 马丽娟 ZHOU Hong-liang;WANG Hai-dan;WANG Ze-kun;MA Li-juan(Department of Pharmacy,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029;Department of Pharmacology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029;The First Clinical Medical College,Nanjing University of Traditional Chinese Medicine,Nanjing 210046)

机构地区：[1]南京中医药大学附属医院药学部,南京210029 [2]南京中医药大学附属医院基础药理实验室,南京210029 [3]南京中医药大学第一临床医学院,南京210046

出　　处：《中南药学》2024年第1期43-47,共5页Central South Pharmacy

基　　金：国家自然科学基金项目(No.82003834)。

摘　　要：目的 研究丹皮酚多晶型(晶型Ⅰ~Ⅲ)的药动学特征及抗痛经作用差异。方法 大鼠单次灌胃给予丹皮酚的3种晶型各138 mg·kg^(-1),用超高效液相色谱法测定血浆中丹皮酚的质量浓度,分析不同晶型丹皮酚的药动学差异;采用雌激素与缩宫素建立大鼠原发性痛经模型,多次灌胃给予丹皮酚3种晶型各138 mg·kg^(-1),通过行为学检测各组大鼠扭体潜伏期、扭体次数,ELISA试剂盒检测子宫组织中前列腺素E_(2)、一氧化氮、肿瘤坏死因子α;HE染色检测子宫组织病理变化。结果 采用非房室模型拟合计算丹皮酚晶型Ⅰ~Ⅲ的主要药动学参数,C_(max)分别为(0.98±0.23)、(1.34±0.24)、(1.88±0.38)μg·m L^(-1),t_(max)分别为(120.00±0.00)、(36.00±13.42)、(15.00±0.00)min,AUC_(0~7 h)分别为(144.62±24.46)、(97.64±24.14)、(104.32±20.25)min·μg·m L^(-1),t_(1/2)分别为(31.80±5.19)、(27.57±4.24)、(28.34±4.74)min,MRT_(0~7 h)分别为(126.74±6.86)、(60.49±5.27)、(50.82±3.17)min。丹皮酚对原发性痛经模型大鼠具有治疗作用,不同晶型药效学结果存在一定差异,Ⅰ晶型在减少大鼠扭体次数、改善子宫炎症因子水平及病变等方面更具优势。结论 丹皮酚晶型Ⅰ溶解、吸收速度慢于其他晶型,能较好地维持血药浓度,其抗痛经作用亦优于其他晶型,具有良好的开发和应用前景。Objective To determine the pharmacokinetic characteristics and difference in antidysmenorrhea effect of paeonol polymorphic forms (crystal formsⅠ~Ⅲ).Methods SD rats were orally administered with 3 crystal forms of paeonal at a dose of 138 mg·kg~(-1).The plasma concentrations of paeonal were determined with ultra-high-performance liquid chromatography.Estrogen and oxytocin were used to establish a rat model of primary dysmenorrhea (PD).The rats were orally administered with 3 crystal forms of paeonal at a dose of 138 mg·kg^(-1) repeatedly.Writhing latency and times of PD rats in each group were tested by behavioral assessment.ELISA kits were used to measure the levels of prostaglandin E_(2),nitric oxide,and tumor necrosis factor α in the uterine tissues,and HE staining was performed to evaluate histopathological changes in the uterine tissues.Results The main pharmacokinetic parameters of paeonal formⅠ,Ⅱ,andⅢwhich were calculated by the noncompartment model as follows:C_(max) was (0.98±0.23),(1.34±0.24),and (1.88±0.38)μg·mL^(-1);t_(max) was (120.00±0.00),(36.00±13.42),and (15.00±0.00) min;AUC_(0~7 h) was (144.62±24.46),(97.64±24.14),and (104.32±20.25) min·μg·mL^(-1),t_(1/2) was (31.80±5.19),(27.57±4.24),and(28.34±4.74) min;and MRT_(0~7h )was (126.74±6.86),(60.49±5.27),and (50.82±3.17) min.Paeonol had positive effect on PD rats,while different crystal forms resulted in different pharmacodynamic expressions.Crystal formⅠhad advantages in reducing the writhing times in the rats,improving the level of inflammatory factors and pathological changes in the uterus.Conclusion The dissolution and absorption rate of paeonal formⅠare slower than those of other forms,which could better maintain the blood drug concentrations.Moreover,the anti-dysmenorrheal effect of formⅠis also superior to other forms,indicating its promising potential in development and application.

关 键 词：丹皮酚 多晶型 药动学 药效差异 

分 类 号：R283[医药卫生—中药学] R286[医药卫生—中医学]