吴茱萸碱磷脂复合物自微乳给药系统的胃溃疡靶向效应及保护作用评价

Evaluation of targeting effect and protective effect of evodiamine phospholipid complex self-emulsifying drug delivery system on gastric ulcer

目的对吴茱萸碱磷脂复合物自微乳给药系统(evodiamine phospholipid complex self-emulsifying drug delivery system,Evo-PC-SMEDDS)的胃溃疡靶向效应进行评价,并验证其药效。方法通过分析荧光成像结果与激光共聚焦显微镜荧光成像结果,对该制剂的胃溃疡靶向性做出评价;通过胃组织形态学观察、HE染色结果,评价Evo-PC-SMEDDS对乙醇诱导的大鼠胃溃疡模型的改善作用,并计算胃溃疡指数、胃溃疡抑制率对胃溃疡情况进行量化和评分;通过测定胃分泌物与氧化应激相关因子,推测Evo-PC-SMEDDS可能的作用机制。结果动物荧光成像结果显示,Evo-PC-SMEDDS在大鼠体内存在胃滞留。通过激光共聚焦显微镜观察到,荧光探针FITC标记的Evo-PC-SMEDDS集中分布于模型大鼠的溃疡黏膜表面。药效学结果与HE染色分析结果均显示,Evo-PC-SMEDDS对乙醇诱导的大鼠胃溃疡模型有较好的保护作用,且测得给药组大鼠胃组织中的MPO和NO含量显著降低(P<0.01)。且与吴茱萸碱组相比,其胃组织中GSH水平显著提高(P<0.01),SOD活力更强,MDA含量更低。结论Evo-PC-SMEDDS在胃内滞留时间达到6 h,明显长于在正常大鼠的胃内滞留时间,推断Evo-PC-SMEDDS以胃内滞留方式实现溃疡部位的特异性分布。Evo-PC-SMEDDS对乙醇诱导的大鼠胃溃疡具有显著的保护作用,可通过口服给药方式及时、有效地抑制胃溃疡大鼠胃组织中过氧化脂质的产生,抑制胃液中H+分泌和胃蛋白酶的活性,减轻大鼠的胃溃疡损伤程度。

Objective To evaluate the gastric ulcer targeting effect of evodiamine phospholipid complex self-emulsifying drug delivery system(Evo-PC-SMEDDS)and verify its efficacy.Methods By analyzing the fluorescence imaging results and laser confocal microscope fluorescence imaging results,the gastric ulcer targeting of the preparation was evaluated.The improvement of Evo-PC-SMEDDS on ethanol-induced gastric ulcer model in rats was evaluated through the morphological observation and HE staining results,and the gastric ulcer index and gastric ulcer inhibition rate were calculated to quantify and score the gastric ulcer.The possible mechanism of Evo-PC-SMEDDS was inferred by measuring the related factors of gastric secretion and oxidative stress.Results The results of animal fluorescence imaging showed that Evo-PC-SMEDDS had gastric retention in rats.It was observed by laser confocal microscope that Evo-PC-SMEDDS labeled by fluorescent probe FITC were concentrated on the surface of ulcer mucosa in model rats.The results of pharmacodynamics and HE staining showed that Evo-PC-SMEDDS had a good protective effect on ethanol-induced gastric ulcer model in rats.After Evo-PC-SMEDDS was administered,the contents of MPO and NO in gastric tissue decreased significantly(P<0.01).Compared with evodiamine group,the GSH level in stomach tissue of Evo-PC-SMEDDS group was significantly increased(P<0.01),SOD activity was stronger and MDA content was lower.Conclusion The retention time of Evo-PC-SMEDDS in the stomach reached 6 h,which was significantly longer than that in the stomach of normal rats.It was inferred that Evo-PC-SMEDDS realized the specific distribution of ulcer sites by gastric retention.Evo-PC-SMEDDS has a significant protective effect on ethanol-induced gastric ulcer in rats.It can timely and effectively inhibit the production of lipid peroxide in gastric tissue of rats with gastric ulcer,inhibit the secretion of H+in gastric juice and the activity of pepsin,and alleviate the degree of gastric ulcer injury in rats.