α-菠菜甾醇对小鼠小肠段药物转运体P-gp和PEPT1表达的影响

Influence of α-spinasterol on expression of P-gp and PEPT1 in small intestine of mice

以酒石酸泰乐菌素为底药,探讨α-菠菜甾醇对小鼠小肠段药物转运体P-gp和PEPT1表达的影响。48只小鼠分为4组:α-菠菜甾醇组,酒石酸泰乐菌素组,α-菠菜甾醇和酒石酸泰乐菌素混合组,生理盐水对照组。每组按0.2 m L·10 g^(-1)体质量的剂量每天灌胃一次,共灌胃5 d,分别在1,3,5 d后处死1批采样。采用免疫组化的方法测定1,3,5 d的小鼠肠道上P-gp和PEPT1的表达。试验结果表明,α-菠菜甾醇组和混合组相对于对照组外排性药物转运体P-gp表达减少,而摄取性药物转运体PEPT1表达增多;酒石酸泰乐菌素组的外排性药物转运体P-gp表达增多,摄取性药物转运体PEPT1表达减少;且都随着用药时间的延长差异增大。表明α-菠菜甾醇具有抑制药物转运体P-gp表达和促进药物转运体PEPT1表达的作用。

In order to research the effect of α-spinasterol on the intestine transporters P-gp and PEPT1 when the ty-lenol tartrate was introduced as a substrate, 48 mice were equally divided into 4 treatment groups： α-spinasterol group, tylenol tartrate group, mixed （α-spinasterol and tylenol tartrate） group, and normal saline group which was used as control group. The formulations were administered by oral gavage with a dose of 0. 2 mL＆#183;10 g^-1 depending on body weight of mice. The small intestine samples of the dissected mice were excised at predetermined time inter-vals （1, 3, 5）. The expressions of P-gp and PEPT1 on the mice intestines were detected by immunohistochemical method at 1, 3, 5 d, respectively. The results showed that the protein expression of P-gp was distinctly reduced inα-spinasterol and mixed groups, and the protein expression of PEPT1 was increased in these 2 groups compared with normal saline group. However, the protein expression of P-gp was increased and the protein expression of PEPT1 was decreased in tylenol tartrate group compared with normal saline group. The difference was more obvious with time pass by. In summary, α-spinasterol had an obvious impact on intestine transporters, including inhibiting P-gp ex-pression and inducing PEPT1 expression.