电针联合奥美拉唑保护NSAIDs大鼠胃溃疡的增效作用评价

Evaluation of synergistic effect of electroacupuncture combined with Omeprazole on gastric ulcer protection in NSAIDs rats

目的:评价电针足三里与不同剂量奥美拉唑联用保护吲哚美辛所致大鼠胃溃疡的增效作用。方法:48只雄性SD大鼠随机分为8组:空白组、模型组、奥美拉唑低剂量组(5 mg/kg,Omeprazole L)、奥美拉唑中剂量组(10 mg/kg,Omeprazole M)、奥美拉唑高剂量组(20 mg/kg,Omeprazole H)、电针联合奥美拉唑低剂量组(E+Omeprazole L)、电针联合奥美拉唑中剂量组(E+Omeprazole M)、电针联合奥美拉唑高剂量组(E+Omeprazole H),每组6只;末次给药前1 h,除空白组外各组以吲哚美辛(40 mg/kg,腹腔注射)制备胃溃疡模型;造模后7 h取材,观察胃黏膜大体外观及胃、肠组织病理形态,对胃黏膜外观及病理损伤作评分。结果:模型组大鼠胃黏膜损伤严重,黏膜表面部分变薄,见点线状出血或糜烂、溃疡灶,病理病变以黏膜层出现红细胞及上皮细胞变性缺损为主。小肠黏膜病理病变呈轻度损伤,见绒毛纹状边缘脱落消失,上皮细胞空泡化。(1)与模型组比较,干预各组胃黏膜大体外观及病理病变改善,胃黏膜损伤评分降低(P<0.05,P<0.01)。除Omeprazole L组外,其余各组病理评分均较模型组降低(Omeprazole H组P=0.08,余P<0.01)。以Omeprazole M组、E+Omeprazole M组、E+Omeprazole H组损伤抑制率最高;(2)Omeprazole 3个剂量组间比较:与Omeprazole L组、Omeprazole H组比较,Omeprazole M组胃黏膜大体外观及病理病变减轻,胃黏膜损伤分数及病理评分降低(P<0.01,P<0.05);(3)E+Omeprazole 3个剂量组间比较:与E+Omeprazole L组比较,E+Omeprazole M组、E+Omeprazole H组胃黏膜大体外观损伤減轻,损伤分数明显降低(P<0.05,P<0.01);(4)同剂量Omeprazole组与E+Omeprazole组间比较:与相同剂量Omeprazole组比较,E+Omeprazole L组、E+Omeprazole H组胃黏膜大体外观、病理病变减轻,损伤分数降低(P<0.05,P<0.01),病理评分呈降低趋势(P=0.1,P=0.08);(5)模型组小肠黏膜轻度损伤,绒毛纹状边缘部分消失脱落,上皮细胞浆空泡。与模型组比较,Omeprazole H组小肠黏膜病理形态损伤明显加重,见黏膜出血、上皮层细胞变性坏死,固有层崩解;其余各组小肠黏膜损伤未有加重趋势。结论:对吲哚美辛所致大鼠急性胃溃疡,电针联合低剂量、高剂量奥美拉唑具有胃黏膜保护增效作用,电针的联合应用可抵抗高剂量奥美拉唑加重吲哚美辛所致小肠损伤。

Objective:To evaluate the synergistic effect of electroacupuncture at Zusanli acupoint combined with different doses of Omeprazole on the protection of Indomethacin-induced gastric ulcer in rats.Methods:48 male SD rats were randomly divided into 8 groups:blank group,model group,low-dose Omeprazole(5 mg/kg,Omeprazole L)group,medium-dose Omeprazole(10 mg/kg,Omeprazole M)group,high-dose Omeprazole(20 mg/kg,Omeprazole H)group,electroacupuncture combined with low-dose Omeprazole(E+Omeprazole L)group,electroacupuncture combined with medium-dose Omeprazole(E+Omeprazole M)group,and electroacupuncture combined with high-dose Omeprazole(E+Omeprazole H)group,with 6 rats in each group.At 1 h before the last administration,the gastric ulcer model was prepared by Indomethacin(40 mg/kg intraperitoneally injected)in all groups except the blank group.The gross appearance of gastric mucosa and pathological morphology of gastric and intestinal tissues were observed 7 h after modeling,and the appearance and pathological damage of gastric mucosa were scored.Results:In the model group,the gastric mucosa was seriously damaged,and the mucosal surface was partially thinner,with linear bleeding,erosion or foci of ulcer.The pathological changes were mainly red cell and epithelial cell degeneration defect in the mucosal layer.The pathological changes of small intestinal mucosal lesions were slightly damaged,and the villous striate margin was shed and the epithelial cells vacuolated.(1)Compared with the model group,the gross appearance and pathological changes of gastric mucosa in each intervention group were improved,and the gastric mucosal injury score was decreased(P<0.05,P<0.01).Except for Omeprazole L group,the pathological scores of other groups were lower than those of model group(Omeprazole H group P=0.08,the rest P<0.01).The damage inhibition rate was the highest in the Omeprazole M group,E+Omeprazole M group and E+Omeprazole H group.(2)Comparison among the three doses groups of Omeprazole:compared with Omeprazole L group and Omeprazole H group,the gross appearance and pathological changes of gastric mucosa were significantly reduced,and the gastric mucosal injury score and pathological score were decreased in Omeprazole M group(P<0.01,P<0.05).(3)Comparison among the three doses groups of E+Omeprazole:compared with E+Omeprazole L group,the gross appearance injury of gastric mucosa was reduced,and the gastric mucosal injury score were significantly decreased in E+Omeprazole M group and E+Omeprazole H group(P<0.05,P<0.01).(4)Comparison among the same dose of Omeprazole groups and the E+Omeprazole groups:compared with the same dose of Omeprazole group,the gross appearance and pathological changes of gastric mucosa in E+Omeprazole L group and E+Omeprazole H group were alleviated,the damage scores were decreased(P<0.05,P<0.01),and the pathological scores showed a decreasing trend(P=0.1,P=0.08).(5)In the model group,the small intestinal mucosa was slightly damaged,the villous striate margin was partially disappeared and exfoliated,and the epithelial cytoplasm vacuolated.Compared with the model group,the pathological changes of small intestinal mucosa in Omeprazole H group were significantly aggravated,including mucosal bleeding,degeneration and necrosis of epithelial cells and disintegration of lamina propria.There was no aggravation of intestinal mucosal injury in other groups.Conclusion:Electroacupuncture combined with low-dose and high-dose Omeprazole has protective and synergistic effect on gastric mucosa of Indomethacin-induced acute gastric ulcer in rats.The combined application of electroacupuncture can prevent high-dose of Omeprazole from aggravating small intestinal injury caused by Indomethacin.