苗药良姜胃疡胶囊对胃溃疡模型大鼠的预防作用及机制研究

目的:研究苗药良姜胃疡胶囊对胃溃疡大鼠模型的预防作用及机制。方法:将大鼠随机分为正常组(生理盐水)、模型组(生理盐水)、阳性对照组(奥美拉唑,0.02 g/kg)和良姜胃疡胶囊低、中、高剂量组(0.3、0.6、1.2 g/kg),每组12只。每天灌胃给药1次,连续给药1周。末次给药1 h后,除正常组外,其余各组大鼠均灌胃无水乙醇复制胃溃疡模型。造模1 h后,测定各组大鼠胃液量、胃液pH、胃蛋白酶活力、胃溃疡面积及胃溃疡抑制率;苏木精-伊红(HE)染色后显微镜下观察各组大鼠胃黏膜组织病理学变化,酶联免疫吸附试验法检测各组大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平;Western blot法检测各组大鼠胃组织中核转录因子κB(NF-κB)通路相关蛋白磷酸化核因子κB亚基65(p-NF-κB p65)、磷酸化核因子κB抑制蛋白α(p-IκBα)]的水平。结果:与正常组比较,模型组大鼠胃液量、胃蛋白酶活力、胃溃疡面积和血清中TNF-α、IL-6水平及胃组织中p-NF-κB p65、pIκBα水平均显著增加/升高(P<0.05),胃液p H显著降低(P<0.01);胃组织黏膜充血红肿、黏膜上皮细胞缺损明显、腺体结构破坏、细胞结构不完整。与模型组比较,阳性对照组和良姜胃疡胶囊中、高剂量组大鼠胃液量、胃蛋白酶活力、胃溃疡面积和TNF-α、IL-6水平均显著减少/降低(P<0.05或P<0.01),胃液p H显著升高(P<0.05);胃组织黏膜正常、腺体破坏减轻、细胞结构基本完整;良姜胃疡胶囊高剂量组大鼠胃组织中p-NF-κB p65、p-IκBα水平显著降低(P<0.05)。结论:良姜胃疡胶囊可通过升高胃液pH,抑制胃蛋白活力,减少炎症因子TNF-α、IL-6的释放,抑制NF-κB通路相关蛋白表达,从而发挥其对胃溃疡的预防作用。

Study on Provention Effect and Mechanism of Miao Medicine Liangjiang Weiyang Capsule on Gastric Ulcer Model Rats

OBJECTIVE:To study the protective effect and mechanism of Miao medicine Liangjiang weiyang capsule on gastric ulcer model rats.METHODS:Rats were randomly divided into normal group(normal saline),model group(normal saline),positive control group(omeprazole,0.02 g/kg)and Liangjiang weiyang capsule low-dose,medium-dose and high-dose groups(0.3,0.6,1.2 g/kg),with 12 rats in each group.All rats were intragastrically administered once a day for consecutive one week.1 h after last administration,all rats except those in normal group were given the absolute ethanol to induce gastric ulcer model.1 h after modeling,gastric juice volume,gastric juice pH,pepsin activity,gastric ulcer area and inhibitory rate of gastric ulcer were recorded in each group.Histopathological changes of gastric mucosa in rats of each group were observed by HE staining.The serum levels of TNF-α and IL-6 were determined by ELISA.The expression of nuclear factor-κB pathway related protein(p-NF-κB p65,p-I κBα)in gastric tissue of rats were determined by Western blot.RESULTS:Compared with normal group,gastric juice volume,pepsin activity,gastric ulcer area,TNF-α and IL-6 levels in serum,p-NF-κB p65 and p-IκBα levels in the gastric tissue were significantly increased/rised(P<0.05),while gastric juice pH was significantly decreased(P<0.01);there were gastric mucosal hyperemia and redness,obvious defect of mucosal epithelial cells,destruction of gland structure and incomplete cell structure.Compared with model group,gastric juice volume,pepsin activity,gastric ulcer area and the levels of TNF-α and IL-6 were reduced/decreased significantly in positive control group,Liangjiang weiyang capsule medium-dose and high-dose groups(P<0.05 or P<0.01),while pH value of gastric juice was increased significantly(P<0.05);gastric mucosa was normal,gland destruction was alleviated and cell structure was intact.The levels of p-NF-κB p65 and p-IκBα in gastric tissue were significantly decreased in Liangjiang weiyang capsule high-dose groups(P<0.05).CONCLUSIONS:Liangjiang weiyang capsule play a role to protect gastric ulcer by increasing gastric juice pH,inhibiting pepsin activity,reducing the release of inflammatory factors as TNF-α,IL-6 and inhibiting the expression of NF-κB pathway related protein.