目的：探讨胃苏颗粒(WSG)对幽门螺杆菌诱导的慢性萎缩性胃炎(CAG)动物模型的影响及其作用机制。方法：50只SD大鼠随机分为对照组、模型组和WSG低、中、高剂量组。除对照组外,其余组建立幽门螺杆菌感染的CAG模型。从第8周开始,WSG每日灌胃WSG(8、16、32? mg/kg),连续4周。试验结束时,通过HE染色评估胃黏膜损伤的组织病理学改变。采用qPCR和Western blot分析胃组织中LATS2、TAZ 的mRNA和蛋白表达。此外,用幽门螺杆菌感染GES-1细胞,并用WSG对其进行干预。采用CCK-8试验分析细胞活力,并分析Hippo/TAZ信号通路表达情况。结果：干预4周后,WSG各剂量组胃粘膜损伤明显减轻,胃粘膜糜烂长度明显缩短,UI评分和炎症评分均呈剂量依赖性降低(P<0.01)。幽门螺杆菌可显著增加TAZ的表达,并降低 LATS2的表达。WSG治疗以剂量依赖的方式逆转了TAZ和 LATS2表达的变化,特别是与CAG组相比,WSG中、高剂量的TAZ和 LATS2蛋白和mRNA表达表现出显著差异(P<0.05)。与幽门螺杆菌感染组相比,40 μM(83.44±5.46)和20 μM WSG组(75.47±8.31)的GES-1细胞活力显著增加(P<0.05)。qPCR和免疫荧光染色的结果显示,WSG干预增加了GES-1细胞中LATS2、WWC2表达,但降低了TAZ表达。此外,WWC2 siRNA预处理削弱了WSG诱导的LATS2活化,并促进了TAZ的表达(P<0.05)。结论：幽门螺杆菌诱导CAG的形成与Hippo/TAZ信号通路有关,WSG通过抑制Hippo/TAZ信号传导发挥了其胃肠道保护作用。

Objective：To investigate the effect of Weisu granule (WSG) on Helicobacter pylori-induced chronic atrophic gastritis (CAG) animal model and its mechanism. Methods: 50 SD rats were randomly divided into control group, model group and low, medium and high dose WSG groups. CAG model of Helicobacter pylori infection was established in the other groups except the control group. Except for the control group, the other groups were induced withSH. pylori suspension to establish CAG model. From the 8th week, WSG group received an administration of different concentrations of WSG (8, 16, 32 mg/kg) every day for 4 weeks. At the end of the experiment, the histopathological changes of gastric mucosal injury were evaluated by HE staining. Quantitative RT-PCR and Western blot were used to analyze the mRNA and protein expression of LATS2 and TAZ in gastric tissue. The expression of LATS2 and TAZ mRNA and protein in gastric tissue was analyzed by qPCR and western blot, respectively. Moreover, GES-1 cells were infected bySH. pylori, and intervened with WSG in vitro. Cell viability were detected by CCK-8 assay. To further investigate the potential mechanisms of WSG, the expression in Hippo/TAZ signaling pathway were measured. Results: After a 4-weeks intervention, the gastric mucosal damage in WSG group was significantly reduced, and the erosion length of gastric mucosal was notably decreased, as well as lower UI scores and inflammation scores in a dose-dependent manner. Helicobacter pylori increased the expression of TAZ and decrease the expression of LATS2. WSG treatment reversed the changes in TAZ and LATS2 expression in a dose-dependent manner, especially compared with the CAG group, WSG medium and high doses of TAZ and LATS2 protein and mRNA expression showed significant differences (P<0.05). Cell viability of GES-1 was increased in 40SμM (83.44±5.46) and 20SμM (75.47±8.31) WSG group compared with theSHelicobacter pyloriSinfection group (P<0.05). qPCR and immunofluorescence staining revealed that WSG intervention increased the expression of LATS2 and WWC2, but reduced the expression of TAZ in GES-1. WWC2 siRNA pretreatment impaired WSG-induced LATS2 activation and promoted the expression of TAZ (P<0.05). Conclusion: The CAG induced by Helicobacter pylori is related to the Hippo/TAZ signaling pathway. WSG plays a protective role in gastrointestinal protective by inhibiting Hippo/TAZ signaling pathway.

陕西省自然科学基金研究计划项目 （20200662）