萎胃汤联合西米替丁对慢性萎缩性胃炎模型大鼠胃黏膜修复及Wnt通路表达影响

目的:探讨萎胃汤联合西米替丁对慢性萎缩性胃炎(CAG)模型大鼠胃黏膜修复及Wnt通路表达影响。方法:选取50只SD大鼠,分为正常组和模型组,正常组10只,模型组40只,模型组采用MNNG造模法建立CAG模型,将造模成功后的36只大鼠随机分为模型对照组、西药组、中西药联合组,每组12只。按设计分别连续灌胃8周,然后处死大鼠,并采集血清、胃液及胃组织标本。观察处死前各组大鼠一般情况及胃黏膜病理形态学变化,检测胃液总胃酸度,采用酶联免疫吸附法检测血清胃泌素(GAS)、前列腺素E2(PGE2)水平,比色法检测组织(PP)水平,免疫组化法检测胃黏膜微血管密度(MVD)、血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量及胃组织糖原合成酶及酶-3(GSK-3β)、β-链蛋白(β-catenin)及环氧化酶-2(COX-2)蛋白表达情况。结果:正常组大鼠体重明显增长,胃黏膜厚度、腺体数量正常,无坏死及缺损;模型对照组大鼠体重增长不明显,胃黏膜变薄,腺体数量大量减少,胃黏膜出现糜烂、缺损;西药组大鼠体重略有增加,胃黏膜略有增厚,腺体数量部分减少,有少量胃黏膜出现糜烂、缺损;中医药联合组大鼠体重显著增加,厚度基本正常,腺体无明显减少,未见胃黏膜出现糜烂、缺损;与正常组对比,模型对照组大鼠总胃酸度、MVD、MVD、GAS、PP、PGE2、SOD、GSK-3β显著降低,MDA、β-catenin、COX-2显著升高,差异有统计学意义(P<0.05);药物干预后,与模型对照组对比,西药组、中西药联合组大鼠总胃酸度、MVD、MVD、GAS、PP、PGE2、SOD、GSK-3β显著升高,MDA、β-catenin、COX-2显著降低,中西药联合组大鼠改善程度显著高于西药组,差异有统计学意义(P<0.05)。结论:萎胃汤联合西米替丁可有效改善慢性萎缩性胃炎模型大鼠胃黏膜萎缩的病理状态,促进胃黏膜微血管新生,抑制胃黏膜氧化应激反应,修复受损的胃黏膜,改善胃黏膜酸功能,其机制可能与调节Wnt通路相关的GSK-3β、β-catenin、COX-2异常表达,进而阻断Wnt通路异常激活,修复甚至逆转胃黏膜萎缩相关。

EEffect of Weiwei Decoction Combined with Cimetidine on Gastric Mucosal Repair and Wnt Pathway Expression in Rats with Chronic Atrophic Gastritis

Objective:To investigate the effect of Weiwei Decoction combined with Cimetidine on gastric mucosal repair and Wnt pathway expression for rats with chronic atrophic gastritis(CAD).Methods:Fifty SD rats were divided into normal group and model group,10 in the normal group and 40 in the model group.The model group used MNNG modeling method to establish CAG model,and 36 rats after successful modeling were randomly divided into models.The controlled group,the western medicine group,and the Chinese and western medicine combined group,12 in each group.The rats were continuously perfused for 8 weeks according to the design,then the rats were sacrificed,and serum,gastric juice and gastric tissue samples were collected.The general conditions of the rats in each group and the pathological changes of gastric mucosa were observed before the death.The total gastric acidity of gastric juice was detected.The levels of serum gastrin(GAS)and prostaglandin E2(PGE2)were detected by enzyme-linked immunosorbent assay.Tissue(PP)level,immunohistochemical detection of gastric mucosal microvessel density(MVD),serum superoxide dismutase(SOD),malondialdehyde(MDA)content and gastric tissue glycogen synthase and enzyme-3(GSK-3β),β-catenin(β-catenin)and cyclooxygenase-2(COX-2)protein expression.Results:The weight of the rats in the normal group increased significantly,the thickness of the gastric mucosa and the number of glands were normal,and there was no necrosis or defect.The weight gain of the model controlled group was not obvious,the gastric mucosa became thinner,the number of glands decreased,and the gastric mucosa appeared erosion.Defects;the weight of the rats in the western medicine group increased slightly,the gastric mucosa increased slightly,the number of glands decreased,and a small amount of gastric mucosa appeared erosion and defect.The weight of the Chinese medicine combined group was significantly increased,the thickness was basically normal,and the gland was not significantly reduced,there was no erosion or defect in the gastric mucosa.Compared with the normal group,the total gastric acidity,MVD,MVD,GAS,PP,PGE2,SOD,GSK-3βin the model controlled group were significantly decreased,MDA,β-catenin,COX-2 increased significantly,the difference was statistically significant(P<0.05).After drug intervention,compared with the model controlled group,the total gastric acidity,MVD,MVD,GAS,PP,PGE2 of the western medicine group and the Chinese and western medicine combined group.SOD and GSK-3βwere significantly increased,MDA,β-catenin and COX-2 were significantly decreased.The improvement degree of rats in the combination group was significantly higher than that in the western medicine group(P<0.05).Conclusion:Weiwei Decoction combined with Cimetidine can effectively improve the pathological state of gastric mucosal atrophy in rats with chronic atrophic gastritis,promote microvascular angiogenesis,inhibit gastric mucosal oxidative stress,repair damaged gastric mucosa,and improve gastric mucosal acidity.The function may be related to the abnormal expression of GSK-3β,β-catenin and COX-2,which is involved in the regulation of Wnt signaling pathway,thereby blocking the abnormal activation of Wnt pathway and reversing gastric mucosal atrophy.