郭颖媛　冯强　杨运霞　马新生　郭明霞　杜丹丹　佘延芬

摘要 目的：探究黄连素对幽门螺杆菌感染小鼠胃黏膜上皮细胞损伤的保护作用。方法：选取25只雄性BALB/c小鼠，随机分为对照组，模型组，低剂量组，中剂量组，高剂量组，每组5只。其中对照组小鼠按0.2 mL/只灌胃生理盐水和布氏肉汤，其他4组均以0.2 mL/只灌胃幽门螺杆菌NCTC11637菌液构建幽门螺杆菌感染模型。低剂量组，中剂量组，高剂量组在建模后分别灌服25 mg/kg、50 mg/kg和100 mg/kg黄连素，1次/d，连续2周。对照组、模型组灌服5 mL/kg 0.5%羧甲基纤维素钠;用CCK-8法评估小鼠胃黏膜上皮细胞活力;ELISA法检测细胞上清IL-1β、IL-8、IL-4、IL-10的水平;流式细胞仪分析细胞凋亡率，免疫印迹法检测细胞中Bax和Cl-caspase-3的表达。结果：与对照组比较，模型组的细胞活力显著下降（P<0.05），而IL-1β、IL-8、IL-4、IL-10水平、细胞凋亡率以及Bax和Cl-caspase-3的表达均显著增加（P<0.05）;与模型组比较，低、中、高剂量组的细胞活力明显增加（P<0.05），而IL-1β、IL-8、IL-4、IL-10水平、细胞凋亡率以及Bax和Cl-caspase-3的表达均显著降低（P<0.05）。结论：黄连素可减轻幽门螺杆菌感染对小鼠胃黏膜上皮细胞的炎性损伤。

关键词 黄连素;幽门螺杆菌;炎症介质;细胞凋亡;白細胞介素-1β;白细胞介素-8;胃黏膜;细胞活力

Abstract Objective：To explore the protective effects of berberine on the injury of gastric mucosal epithelial cells in mice model with helicobacter pylori.Methods：25 male BALB/c mice were selected and randomly divided into the control group，model group，low-dose experimental group，medium-dose experimental group and high-dose experimental group，with 5 in each group.The mice in the control group were given 0.2 mL/each with normal saline and brucella broth.The other four groups were all given 0.2 mL/each helicobacter pylori NCTC11637 bacterial solution to construct the helicobacter pylori infection model.After successful modeling，the low-dose experimental group，the middle-dose experimental group，and the high-dose experimental group were given 25 mg/kg，50 mg/kg and 100 mg/kg berberine，respectively.1 time per day for 2 consecutive weeks.The control group and model group were given sodium carboxymethyl cellulose solution at the dose of 5 mL/kg by gavage respectively.Mouse gastric mucosal epithelial cells viability was assessed using CCK-8.The levels of IL-1β，IL-8，IL-4，IL-10 in cell supernatant were detected by enzyme-linked immunoassay（ELISA）.Cell apoptosis were analyzed by flow cytometry.The expression of Bax and Cl-caspase-3 in the cells was detected by western blotting.Results：Compared with the control group，cell viability decreased significantly in the model group（P<0.05），while the contents of IL-1β，IL-8，IL-4，IL-10，apoptosis rate and expression of Bax and Cl-caspase-3 were significantly increased（P<0.05）.Compared with the model group，cell viability was significantly increased in low，medium and high dose groups（P<0.05），while the contents of IL-1β，IL-8，IL-4，IL-10，apoptosis rate and expression of Bax and Cl-caspase-3 were significantly decreased（P<0.05）.Conclusion：Berberine can reduce the inflammatory damage of helicobacter pylori infection on gastric mucosal epithelial cells in mice.

Keywords Berberine; Helicobacter pylori; Inflammatory factors; Apoptosis; Interleukin 1β; Interleukin 8; Gastric mucosal; Cell vitality

中图分类号：R284;R392.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.18.008

幽门螺旋杆菌是一种公认的病原体，世界上多达一半的人慢性感染幽门螺旋杆菌[1]，幽门螺旋杆菌是导致消化性溃疡和慢性胃炎发生的重要原因，也是十二指溃疡发生的启动因子[2]。黄连素，又名小檗碱，属异喹啉类生物碱，是植物黄连的根状茎中提取的主要有效成分[3]。临床上黄连素被用来治疗消化性溃疡、胃炎和消化性或感染性腹泻等疾病[4]。最新研究表明，黄连素具有良好的抗菌、抗炎等作用[5]。有研究报道黄连素在多种疾病中均具有显著的疗效，例如宋菊敏等[6]在研究中发现黄连素可明显降低糖尿病大鼠高胰岛素血症，改善脂类代谢障碍，同时黄连素还具有抗氧化作用。……