清热化湿方调节PI3K-AKT信号诱导自噬维持胃黏膜稳态防治幽门螺杆菌感染相关胃癌的机制  

Qingre Huashi Decoction Preventing Onset of Hp-Associated Gastric Cancer by Regulating PI3K-AKT Signal Pathway Induced Autophagy to Maintain Gastric Mucosa Homeostasis

作　　者：许文彬 陈远能[2] 张涛[2] 陈玉[2] 李华燕[3] 平倩[2] 

机构地区：[1]浙江省萧山医院胃肠外科,浙江萧山311200 [2]广西中医药大学附属瑞康医院消化科,广西南宁530011 [3]江门市第二人民医院,广东江门529050

出　　处：《中华中医药学刊》2016年第10期2335-2338,I0002,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81360531)

摘　　要：目的:通过观察胃癌小鼠组织病理学、超微结构、P110、P-AKT、beclin-1及CDK1等指标变化,分析清热化湿方药防治胃癌的可能机制。方法:100只雄性Balb-c小鼠按体质量随机分为5组,即正常组、模型组及治疗组(低、中、高剂量)每组20只,应用Hp感染联合N-甲基-N-亚硝基脲自由饮水法诱导胃癌模型,第30周起分组给药即模型组予蒸馏水灌胃;治疗组予低、中、高剂量清热化湿方灌胃;连续10周。末次给药后处死全部小鼠,分离胃组织,予HE染色及透射电镜检测胃黏膜组织病理学及超微结构变化;予荧光定量PCR及免疫应迹法检测胃黏膜P110、P-AKT、beclin-1及CDK1表达。结果:模型组小鼠胃体、胃窦黏膜重度慢性炎症100%,不典型增生占65.3%,低分化腺癌57%;治疗组小鼠胃窦黏膜轻-中度慢性炎症,不典型增生占24%,未见癌变,以中、高剂量组更为明显。与模型组比较,有统计学意义(P<0.05)。电镜下见模型组上皮细胞微绒毛稀疏甚至脱落消失,细胞间复合连接松解消失,核固缩,异染色质块状分布于核膜下,细胞处于坏死期。治疗组可见上皮细胞体积明显变小,核染色质边集、核固缩,核膜断核碎裂;中、高剂量组见上皮细胞明显变小、空泡化,凋亡小体形成,可见自噬。模型组胃黏膜P110、P-AKT、beclin-1及CDK1蛋白及mRNA表达呈上升趋势,治疗组P110、PAKT、beclin-1及CDK1表达明显下降,有统计学意义(P<0.05)。结论:清热化湿方可能通过调控PI3K-AKT信号,诱导细胞自噬,下调beclin-1及CDK1表达而发挥防治胃癌的效用。Objective ： We aimed to explore the mechanism of Qingre Huashi （QRHS） Decoction treating with gastric cancer through the observation of the pathological changes and the ultra structure and the expressions of P110, P- AKT, beclin - 1 and CDK1 in gastric mucosa. Methods ： A total of 100 Balb - c rats according to body weights were randomly divided into normal group, blank group and low dosage intervention group, medium dosage intervention group and high dosage intervention group with 20 rats in each respectively. The gastric cancer models were administrated by Hp infection and n - methyl - n - nitrosourea. The blank group received distilled water and the intervention group was treated with low,medium and high dosage of QRHS Decoction from the 30th week. After l0 weeks,all the rats were killed and the gastric tissues were isolated. The pathological and ultrastructural changes of gastric mucosa were detected by HE staining and transmission electron microscopy. The expressions of CDK1, beclin - 1, P -AKT and P110 were detected by PCR and Western- blot. Results： In the blank group,the mild to severe inflammation in gastric mucosa accounted for 100%. The atypical hyperplasia was accounted for 65.3% and the low differentiation adenocarcinoma accounted for 57%. The inter- vention group had mild to moderate chronic inflammation. The low differentiation adenocarcinoma was 24%. There was no gastric cancer - liked mucosa. Compared with the blank group, there was a statistical significance difference （ P 〈0. 05）. The blank group＇ s epithelial cell microvillus were sparse with shedding vanished and the inter - cellular connec- tion was disappeared and nuclear pyknosis under the electron microscope. The intervention group showed that the epithelial cell became small with vacuolization and apoptotic bodies. The cells became autophagy. The expressions of P110,bec- lin - 1, P - AKT and CDK1 protein and mRNA in the blank group were increased while the intervention group＇ s decreased. The differences were statisti

关 键 词：PI3K-AKT信号 自噬 稳态 胃癌 清热化湿方药 

分 类 号：R285.5[医药卫生—中药学]