绿原酸类成分在正常及心肌肥大大鼠中肠吸收特征的对比

Comparative of Intestinal Absorption Characteristics of Chlorogenic Acid Components in Normal and Myocardial Hypertrophy Rats

关键词:  绿原酸  隐绿原酸  新绿原酸  心肌肥大  肠吸收  药代动力学

Key words:  chlorogenic acid  cryptochlorogenic acid  neochlorogenic acid  myocardial hypertrophy  intestinal absorption  pharmacokinetics

摘要:

目的 比较绿原酸及其同分异构体新绿原酸、隐绿原酸在不同生理状态大鼠不同肠段的吸收特征差异,为绿原酸类成分的临床用药和产品开发提供理论依据。方法 基于大鼠在体肠灌流模型,优化并建立HPLC方法,分别测定低、中、高浓度(100、200、400 μg.mL ^-1)绿原酸、新绿原酸和隐绿原酸在大鼠十二指肠、空肠、回肠、结肠中0~120 min肠灌流液中的含量变化,计算吸收速率常数Ka和表观渗透系数Papp。结果 新绿原酸和隐绿原酸在两种状态大鼠小肠中的吸收机制为被动扩散,绿原酸在空肠和结肠中存在主动转运。在正常大鼠相同肠段,相同质量浓度条件下的绿原酸和隐绿原酸吸收参数Ka值基本无显著性差异。在十二指肠中,新绿原酸在中、低质量浓度条件下,Ka值明显低于绿原酸(P<0.05),在其他肠段的吸收能力与绿原酸和隐绿原酸接近,无显著性差异。在心肌肥大大鼠中,绿原酸、新绿原酸和隐绿原酸吸收参数Ka基本无显著性差异。在正常大鼠中,绿原酸和隐绿原酸在不同肠段中的吸收速率为：十二指肠>回肠>空肠>结肠,新绿原酸为：十二指肠≈回肠>空肠>结肠；在心肌肥大大鼠中,三者的吸收速率为：回肠>十二指肠>空肠>结肠。与正常大鼠比较,病理状态下绿原酸、新绿原酸和隐绿原酸在各肠段的Papp明显增加,Ka在回肠中明显增加。结论 正常状态下,绿原酸和隐绿原酸的肠吸收特征相似,新绿原酸在十二指肠的吸收能力弱于两者；病理状态促进了绿原酸、新绿原酸和隐绿原酸在不同肠段的吸收,最佳吸收部位由十二指肠转变为回肠。研究结果提示以三者为药效物质治疗心血管类疾病时,可以考虑靶向运输至回肠,增加吸收,增强药效。该研究为绿原酸类成分的临床用药和产品开发提供理论依据。

Abstract:

ABSTRACT: OBJECTIVE Compare the absorption characteristics of chlorogenic acid and its isomers neochlorogenic acid and cryptochlorogenic acid in different intestinal segments of rats at different physiological states. METHOD Based on intestinal perfusion model in vivo, the HPLC technique was optimized and established to determine low, medium, and high concentrations (100, 200, 400 μg·mL -1) content changes of chlorogenic acid, neochlorogenic acid and cryptochlorogenic acid in the duodenum, jejunum, ileum and colon for 0-120 min, and the absorption rate constant Ka and the apparent absorption coefficient Papp were calculated. RESULT The absorption mechanism of neochlorogenic acid and cryptochlorogenic acid in the small intestine of rats in both states is passive diffusion, while chlorogenic acid is actively transported in the jejunum and colon. There was no significant difference in the Ka values of chlorogenic acid and cryptochlorogenic acid absorption parameters under the same mass concentration conditions in the same intestinal segment of normal rats. In the duodenum, under medium and low mass concentration conditions, the Ka value of neochlorogenic acid was significantly lower than that of chlorogenic acid (P<0.05), and its absorption capacity in other intestinal segments was similar to chlorogenic acid and neochlorogenic acid, with no significant difference; There was no significant difference in the absorption parameters Ka of chlorogenic acid, neochlorogenic acid, and Cryptochlorogenic acid among myocardial hypertrophy rats. In normal rats, the absorption rate of chlorogenic acid and cryptochlorogenic acid in different intestinal segments is as follows: duodenum>ileum>jejunum>colon, while neochlorogenic acid is as follows: duodenum≈ileum>jejunum>colon; In myocardial hypertrophy rats, the absorption rate of the three is: ileum>duodenum>jejunum>colon. Compared with normal rats, under pathological conditions, chlorogenic acid, neochlorogenic acid, and cryptochlorogenic acid significantly increased Papp in each intestinal segment and Ka significantly increased in the ileum. CONCLUSION Under normal conditions, the intestinal absorption characteristics of chlorogenic acid and cryptochlorogenic acid are similar, while the absorption capacity of neochlorogenic acid in the duodenum is weaker than both; The pathological state promotes the absorption of chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid in different intestinal segments, with the optimal absorption site transitioning from the duodenum to the ileum. The research results suggest that when using the three components as pharmacological substances to treat cardiovascular diseases, targeted transportation to the ileum can be considered to increase absorption and enhance drug efficacy. This study provides a theoretical basis for the clinical use and product development of chlorogenic acid components.