雪菊水提物对小鼠肠道形态结构的影响及马里苷在大鼠体内肠吸收特性研究

Study on Effect of Water Extract of Xueju(Coreopsis Tinctoria) on IntestinalMorphology and Structure of Mice and Intestinal Absorption Characteristics of Mareinin Rats

目的:探究雪菊水提物对肠组织形态的影响及雪菊水提物中马里苷在肠道的吸收机制。方法:将40只昆明小鼠按每组10只随机分为空白组及雪菊水提物低、中、高剂量组(0.25 g/kg、0.50 g/kg、1.00 g/kg),分别予生理盐水及相应剂量雪菊水提物连续灌胃30 d,通过观察回肠组织病理学变化,探究雪菊水提物对小鼠肠道形态结构的影响。采用大鼠外翻肠囊模型,利用高相液相色谱法(HPLC)测定高、中、低质量浓度(25.0 mg/mL、12.5 mg/mL、6.25 mg/mL)雪菊水提物给药后大鼠不同肠段(十二指肠、空肠、回肠、结肠)、不同时间点(20 min、40 min、60 min、80 min、100 min、120 min)的肠吸收液中马里苷的含量,并计算累积吸收量(Q)和吸收速率常数(Ka)。结果:与空白组小鼠比较,雪菊水提物低、中剂量组小鼠小肠绒毛增高、变粗,高剂量组出现肠腺、杯状细胞数量增多现象。在不同药物质量浓度下,马里苷在大鼠各肠段均呈线性吸收,决定系数R2大于0.96,符合零级吸收速率;随着药物质量浓度的增加,Ka也随之增加;大鼠各肠段吸收速率常数有所差异,在回肠Ka值最大,结肠次之,空肠最小。结论:雪菊水提物对小鼠肠道无毒性;马里苷在大鼠在各肠段中均有吸收,吸收部位主要在回肠、结肠,其吸收机制可能为被动扩散。

Objective:To explore the effect of water extract from Xueju(Coreopsis Tinctoria) on intestinal tissue morphology and the intestinal absorptive mechanism of marein in water extract of Xueju.Methods :Total 40 Kunming mice were randomly divided into the blank group,and low,medium and high dose groups(0.25 g/kg,0.50 g/kg,1.00 g/kg) of water extract of Xueju. The mice in each group were given physiological saline and corresponding water extract of Xueju by gavage for continuous 30 days. By observing the histopathological changes of ileum,the effect of water extract from Xueju on intestinal morphology and structure were investigated. And the model of eversion intestinal sac in rats was used. Marein levels in the intestinal absorption liquid collected in different intestinal segments(duodenum,jejunum,ileum,colon) of rats and different time(20 min,40 min,60 min,80 min,100 min,120 min) were determined by high performance liquid chromatography(HPLC) after administration of water extract of Xueju. with high,medium and low mass concentrations(25.0,12.5,6.25 mg/mL) and the cumulative absorption(Q) and absorption rate constant(Ka) were calculated. Results:Compared with the mice of blank group,the villi of small intestine of mice in the low and medium dose groups increased and became thicker,while the number of intestinal glands and goblet cells increased in the high dose group. Under different drug concentrations,marein was absorbed linearly in each intestinal segment of rats,with the determination coefficient R2 greater than 0.96,which was in line with the zero order absorption rate. With the increase of drug concentration,Ka also increased;the absorption rate constant of each intestinal segment of rats was different,with the largest Ka value in the ileum,the second in the colon,and the smallest in the jejunum. Conclusions:Water extract of Xueju is non-toxic to the intestines of mice. Marein can be absorbed in all intestinal segments of rats,mainly in ileum and colon,and its absorption mechanism may be passive diffusion.