摘要
目的:研究化浊解毒方对慢性萎缩性胃炎大鼠胃组织Hippo/TAZ信号通路及其相关蛋白转录共激活因子PDZ结合基序(TAZ)、肿瘤抑制激酶(LATS2)、哺乳动物不育系20样激酶(MST1)表达的影响。方法:采用联合造模法建立慢性萎缩性胃炎(CAG)大鼠模型成功后随机分为模型组、维酶素0.06 g/kg组、化浊解毒方7、14、28 g/kg组,灌胃治疗12周。采用HE染色法观察胃黏膜组织病理改变,蛋白质印记法(Western Blot)、实时荧光定量PCR技术检测胃黏膜组织中TAZ、LATS2、MST1蛋白和mRNA的表达。结果:与正常组相比,模型组大鼠胃组织TAZ mRNA和蛋白表达水平显著升高,LATS2、MST1 mRNA和蛋白表达水平显著降低;与模型组相比,化浊解毒方组和维酶素组大鼠一般状态、胃黏膜组织病理变化均改善,胃黏膜组织TAZ蛋白和基因表达水平降低,LATS2、MST1蛋白和基因表达水平升高,并且治疗组中以化浊解毒方28 g/kg组作用最为显著。结论:化浊解毒方在CAG大鼠模型中可通过下调胃黏膜组织中TAZ蛋白和基因表达水平,上调LATS2、MST1蛋白和基因的表达水平而起作用,28 g/kg化浊解毒方能显著改善胃黏膜病理情况,在Hippo/TAZ信号通路的调节过程中,下调TAZ蛋白和基因,上调LATS2、MST1均优于维酶素组。
Objective: To study the effect of Huazhuojiedu formula on Hippo/TAZ signal channel and related proteins transcriptional coactivator with PDZ-binding motif(TAZ),large tumor suppressor kinase 2(LATS2) and mammalian sterile 20-like kinase 1(MST1) expression in gastric tissues of rats with chronic atrophic gastritis(CAG).Methods:CAG rat model was established by combining method. All rats were randomly divided into the model group, 0.06 g/kg vitacoenzyme group and three doses of Huazhuojiedu groups(7 g/kg、14 g/kg、28 g/kg),10 in each group. Animals were administered with corresponding drugs for 12 weeks. HE staining was used to observe the pathological changes of gastric tissues. Western Blot and Real-time Quantitative Polymerase Chain Reaction were used to observe expression level changes of protein TAZ,LATS2 and MST1 in gastric tissues.Results: Compared with the control group, the mRNA and protein levels of TAZ in the gastric tissue of the models were significantly increased, the expression levels of LATS2 and MST1 were significantly decreased. Compared with the model group, the general states of rats and pathological changes in gastric tissues in Huazhuojiedu groups and vitacoenzyme group were improved. The mRNA expression and protein levels of TAZ were decreased, while the expression levels of LATS2 and MST1 were increased. 28 g/kg Huazhuojiedu showed the most significant effect. Conclusion: In CAG rat model, Huazhuojiedu formula could play a role by reducing the expression level of TAZ protein and increasing the expression levels of LATS2 and MST1 protein in gastric tissues. Huazhuojiedu formula at 28 g/kg can significantly improve pathological changes of gastric mucous membrane. In the regulation process of Hippo/TAZ signal channel, the negative regulation of TAZ protein and the positive regulation of LATS2 and MST1 are better than those in the vitacoenzyme group.
作者
王彦刚
郝新宇
于仁杰
田雪娇
Wang Yangang;Hao Xinyu;Yu Renjie;Tian Xuejiao(Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011;Hebei University of Chinese Medicine,Shijiazhuang 050200;China University of Petroleum,Beijing 102249)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第3期105-110,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
河北省临床医学优秀人才培养和基础课题研究项目(361025)
