Zeng Jin-hao, Pan Hua-feng, Liu You-zhang, Xu Hai-bo, Zhao Zi-ming, Li Hai-wen, Ren Jin-ling, Chen Long-hui, Hu Xia, Yan Yan
The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Chin J Integr Med. 2016 Apr;22(4):267-75. doi: 10.1007/s11655-015-2131-4. Epub 2015 Apr 14.
To study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).
Sprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.
Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).
Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.
研究胃痞消（WPX）对胃癌前病变（GPL）大鼠胃黏膜上皮细胞中Wnt信号通路相关蛋白的影响。
将Sprague Dawley大鼠随机分为对照组、模型组、维生素辅酶组（0.2 g·kg⁻¹·d⁻¹）、胃痞消高剂量组（H-WPX，15 g·kg⁻¹·d⁻¹）、胃痞消中剂量组（M-WPX，7.5 g·kg⁻¹·d⁻¹）和胃痞消低剂量组（L-WPX，3.75 g·kg⁻¹·d⁻¹）。成功建立GPL模型后，大鼠连续10周经胃管灌胃给予WPX或维生素辅酶。采用免疫组织化学法检测各组大鼠胃黏膜上皮细胞中富含亮氨酸重复序列的G蛋白偶联受体5（Lgr5）、基质金属蛋白酶-7（MMP-7）、Wnt1、Wnt3a和β-连环蛋白的表达差异，并用Image Pro Plus 6.0软件拍照并进行半定量分析。
模型组胃上皮细胞中Lgr5、MMP-7、Wnt1、Wnt3a和β-连环蛋白的表达水平显著高于对照组（P<0.01）。有趣的是，我们还观察到Lgr5⁺细胞，其通常位于胃腺单位底部，随着GPL的发展迁移至胃上皮的腔侧。与模型组和维生素辅酶组相比, L-WPX组中Lgr5、MMP-7、Wnt1和β-连环蛋白的表达水平均下调（P<0.05）。所有WPX组中Wnt3a的表达水平均有类似的下调，但差异无统计学意义（P>0.05）。
我们的研究结果表明，胃痞消治疗GPL的作用机制可能与其对Lgr5、MMP-7、Wnt1、β-连环蛋白表达的抑制作用以及Wnt/β-连环蛋白信号通路的异常激活有关。
