盐酸表异匹罗卡品，一种从小叶毛果芸香叶中分离出的咪唑生物碱，可保护大鼠免受萘普生引起的胃肠道损伤。

Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats.

作者信息

Nicolau Lucas A D, Carvalho Nathalia S, Pacífico Dvison M, Lucetti Larisse T, Aragão Karoline S, Véras Leiz M C, Souza Marcellus H L P, Leite José R S A, Medeiros Jand Venes R

机构信息

Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.

Post Graduation Program in Pharmacology, Federal University of Piauí, Teresina, PI, Brazil.

出版信息

Biomed Pharmacother. 2017 Mar;87:188-195. doi: 10.1016/j.biopha.2016.12.101. Epub 2017 Jan 2.

DOI:10.1016/j.biopha.2016.12.101

PMID:28056423

Abstract

OBJECTIVE

This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats.

METHODS

Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30mg/kg, p.o. or i.p., groups 3-5, respectively) twice daily, for 2days. After 1h, NAP (80mg/kg, p.o.) was given. The control group received only vehicle (group 1) or vehicle+naproxen (group 2). Rats were euthanized on 2nd day, 4h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated.

RESULTS

EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4±0.3U/mg of gastric tissue) and inhibited changes in MDA (70.4±8.3mg/g of gastric tissue) and GSH (246.2±26.4mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group.

CONCLUSION

Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF.

摘要

目的

本研究旨在探讨盐酸表异去甲土木香碱（EPI），一种咪唑生物碱，对萘普生（NAP）诱导的大鼠胃肠道损伤的保护作用。

方法

最初，大鼠每日两次分别用0.5%羧甲基纤维素（赋形剂）或EPI（3、10和30mg/kg，分别经口或腹腔注射，第3 - 5组）预处理2天。1小时后，给予NAP（80mg/kg，经口）。对照组仅接受赋形剂（第1组）或赋形剂+萘普生（第2组）。在NAP处理后4小时的第2天对大鼠实施安乐死。测量胃部病变。收集样本进行组织学评估以及检测谷胱甘肽（GSH）、丙二醛（MDA）、髓过氧化物酶（MPO）和细胞因子水平。此外，评估胃黏膜血流量（GMBF）。

结果

EPI预处理可预防NAP诱导的宏观和微观胃部损伤，最大效应出现在10mg/kg。组织学分析显示，EPI降低了NAP所致损伤的评分。EPI降低了MPO（3.4±0.3U/mg胃组织），并抑制了MDA（70.4±8.3mg/g胃组织）和GSH（246.2±26.4mg/g胃组织）的变化。NAP增加了肿瘤坏死因子-α（TNF-α）水平，而EPI预处理可减轻这种效应。此外，与对照组相比，EPI使GMBF增加了15%。