竹节参总皂苷预防非甾体抗炎药引起肠黏膜损伤

The preventive effect of total saponins of Panax japonicus on nonsteroidal anti-inflammatory drug-induced enteropathy

目的探讨竹节参总皂苷对非甾体抗炎药(NSAID)导致肠黏膜损伤的预防保护作用。方法 5 mg/kg双氯芬酸钠连续2 d灌胃处理,建立NSAID肠黏膜损伤模型。在模型建立的前4 d,竹节参总皂苷组小鼠给予竹节参皂苷灌胃,连续灌胃6 d。异硫氰酸荧光素标记的葡聚糖(FITC-DT)及Evans蓝染色法检测小肠黏膜通透性,HE染色观察小肠黏膜病变,免疫荧光组织化学染色检测肠黏膜上皮细胞的内质网应激反应蛋白葡萄糖转运蛋白78(GRP78)和肿瘤坏死因子α(TNF-α)的表达。结果Evans蓝染色及FITC-DT测定法检测发现模型组小肠黏膜损伤严重,小肠黏膜蓝色斑点密集,通透性显著升高;HE染色观察到模型组小鼠小肠黏膜绒毛上皮细胞发生变性、坏死,同时观察到黏膜下炎细胞浸润,说明成功建立了肠黏膜损伤模型。不同剂量的竹节参总皂苷处理后能减轻肠黏膜损伤,免疫荧光染色发现小肠上皮细胞GRP78和TNF-α的表达明显减少。结论竹节参总皂苷可通过内质网应激途径减轻NSAID所致的小肠黏膜损伤。

Objective To investigate the preventive effect of total saponins of Panax japonicus（ SPJ） on nonsteroidal anti-inflammatory drug（ NSAID）-induced intestinal injuries in mice. Methods NSAID-induced intestinal mucosal damaged models were established by intragastric administration of 5 mg/m L diclofenac sodium in mice for continuous 2 days. Since 4days before the modeling, the mice in the experimental group were given SPJ once a day for 6 days. The small intestinal mucosal permeability was detected by fluorescein isothiocyanate-dextran（ FITC-DT） and Evans blue staining. The small intestinal mucosal lesions were observed by HE staining; immunofluorescence staining was used to determine the expressions of endoplasmic reticulum stress response protein glucose transporter protein 78（ GRP78） and tumor necrosis factor alpha（ TNF-α） in the intestinal mucosal epithelial cells. Results In the model group,small intestinal mucosal injury was serious. Evans blue staining and FITC-DT labeling showed the blue spots were denser and mucosal permeability increased significantly in the model group. HE staining revealed the intestinal mucosal villus degeneration, necrosis,shedding,and inflammatory cell infiltration in the model group,which meant the intestinal mucosal damage models were successfully established. And different concentrations of SPJ protected intestinal mucosa,meanwhile the expressions of GRP78 and TNF- α were significantly reduced in the intestinal epithelial cells as indicated by immunofluorescence staining.Conclusion There is a certain preventive effect of total SPJ on NSAID-induced intestinal injuries via the endoplasmic reticulum stress pathway.