附子水提物对大鼠十二指肠外排转运蛋白和紧密连接蛋白表达的影响 点击下载
| 论文标题： | 附子水提物对大鼠十二指肠外排转运蛋白和紧密连接蛋白表达的影响 |
| 英文标题： | |
| 中文摘要： | 目的：研究附子水提物对大鼠十二指肠组织中3种外排转运蛋白和3种紧密连接蛋白及其基因表达的影响。方法：取32只SD雄性大鼠，随机分为正常组和附子水提物低、中、高剂量组[0.45、0.9、1.8 g/（kg·d），以生药量计算]，每组8只，分别灌胃水和相应药液0.1 mL/kg，连续给药7 d。末次给药后，取大鼠十二指肠肠段，采用Western blotting法检测肠组织中P-糖蛋白（P-gp）、乳腺癌耐药蛋白（Bcrp）、多药耐药蛋白2（Mrp2）为代表的外排转运蛋白和密封蛋白（Claudin-1）、闭合蛋白（Occludin）、闭锁小带蛋白（ZO-1）为代表的紧密连接蛋白的表达水平；采用实时定量聚合酶链式反应法测定上述6种蛋白对应基因的mRNA表达水平。结果：与正常组比较，附子水提物各剂量组大鼠十二指肠组织中P-gp、Mrp2、Bcrp、Claudin-1、Occludin、ZO-1的蛋白表达水平均显著升高（P＜0.01）；附子水提物各剂量组P-gp的mRNA表达水平，附子水提物低、高剂量组Bcrp的mRNA表达水平以及附子水提物中、高剂量组Claudin-1的mRNA表达水平均显著升高，差异均有统计学意义（P＜0.05或P＜0.01），其余基因的mRNA表达水平差异均无统计学意义（P＞0.05）。结论：附子水提物可从mRNA和/或蛋白水平上调3种外排转运蛋白和3种紧密连接蛋白的表达，从而可能与上述外排转运蛋白的其他底物类药物以及以细胞旁路途径为主要转运通道的药物发生相互作用，在临床上联合用药时可考虑对用药剂量作相应调整。 |
| 英文摘要： | OBJECTIVE： To study the effects of Aconitum carmichaelii water extract on the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins as well as their genes in duodenum tissues of rats. METHODS： Thirty-two SD male rats were randomly divided into normal group， A. carmichaelii water extract low-dose， medium-dose and high-dose groups [0.45， 0.9， 1.8 g/（kg·d）， by crude drug]， with 8 rats in each group. They were given water and relevant liquid 0.1 mL/kg intragastrically for consecutive 7 d. After last administration， the duodenal segments of rats were collected. Western blotting assay was used to detect the expression of efflux transporters as P-glycoprotein （P-gp）， breast cancer resistance protein （Bcrp）， multidrug resistance protein 2 （Mrp2） as well as tight junction proteins as Claudin-1， Occludin and ZO-1. mRNA expression of 6 kinds of proteins relevant gene were determined by qRT-PCR respectively. RESULTS： Compared with normal group， the protein expression of P-gp， Mrp2， Bcrp， Claudin-1， Occludin and ZO-1 in duodenum of rats were increased significantly in A. carmichaelii water extract groups （P＜0.01）. mRNA expression of P-gp in A. carmichaelii water extract groups， mRNA expression of Bcrp in A. carmichaelii water extract low-dose and high-dose groups as well as mRNA expression of Claudin-1 in A. carmichaelli water extract medium-dose and high-dose groups were increased significantly， with statistical significance （P＜0.05 or P＜0.01）. There was no statistical significance in mRNA expression of other genes （P＞0.05）. CONCLUSIONS： A. carmichaelii water extract can up-regulate the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins at the level of mRNA and/or protein， thus may interact with other substrates of the aforementioned efflux transporters and drugs with cell bypass pathway as the main transport pathway. In clinical practice， adjustment of dosage may be considered in drug combination. |
| 期刊： | 2019年第30卷第20期 |
| 作者： | 季苗苗，梁新丽，钟友宝，陈来，廖正根 |
| 英文作者： | JI Miaomiao，LIANG Xinli，ZHONG Youbao，CHEN Lai，LIAO Zhenggen |
| 关键字： | 附子；水提物；十二指肠；外排转运蛋白；紧密连接蛋白；细胞旁路；药物相互作用；大鼠 |
| KEYWORDS： | Aconitum carmichaelii；Water extract； Duodenum； Efflux transporter； Tight junction protein； Cell bypass pathway； Drug interaction； Rat |
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