欣胃颗粒对胃癌前病变大鼠STAT3、p-STAT3信号通路的影响

Effects of Xinwei Granule on STAT3 and p-STAT3 Signal Pathway in Rats with Precancerous Lesion of Gastric Cancer

目的探讨欣胃颗粒对胃癌前病变(precancerous lesionof gastric cancer,PLGC)大鼠信号传导及转录活化因子(signal transducers and activators of transcription,STATs)、酪氨酸磷酸化STAT3(p-STAT3)信号通路的影响。方法 96只Wistar大鼠随机分为空白对照组(空白组)16只,造模组80只。采用N-甲基-N′-硝基-亚硝基胍(MNNG)为主的复合因素造模法制备PLGC大鼠模型,将造模成功大鼠随机抽取75只分为模型组、维霉素组、欣胃颗粒低剂量组、欣胃颗粒中剂量组、欣胃颗粒高剂量组,每组15只。空白组随机抽取大鼠15只。空白组予普通标准饲料喂养,并予10mL/kg生理盐水灌胃;欣胃颗粒低、中、高剂量组每日分别给予1.254、2.508、5.016g/kg中药冲剂灌胃;模型组给予10mL/kg生理盐水灌胃;维酶素组将维酶素片研碎制成0.1g/mL的混悬液以10mL/kg灌胃。均每日1次,给药12周。观察各组大鼠的一般状态(包括大鼠皮毛、活动度、进食进水量、粪便、体重及存活情况)和胃黏膜组织病理学的变化,观察其对STAT3、p-STAT3表达的影响。结果与空白组比较,模型组STAT3、p-STAT3表达水平增高(P<0.05)。欣胃颗粒各剂量组大鼠活动度、进食水量、体重等一般状态较模型组好转;与模型组比较,欣胃颗粒低、中、高剂量组,STAT3、p-STAT3表达水平降低,差异均有统计学意义(P<0.05);PLGC即肠上皮化生(intestinal metaplasia,IM)和异性增生(dysplasia,DYS)发生率均显著下降,差异有统计学意义(P<0.05)。与维酶素组比较,欣胃颗粒中、高剂量组IM及DYS发生率均显著下降,差异有统计学意义(P<0.05),欣胃颗粒中、高剂量组STAT3、p-STAT3表达水平下降更显著,差异有统计学意义(P<0.05)。结论欣胃颗粒对PLGC大鼠胃黏膜组织病理具有明显改善作用,可下调STAT3、p-STAT3的表达以达到对抗PLGC的作用。

Objective To study the effects of Xinwei Granule （XG）on signal transducers and activators of transcription （STATs）and tyrosine phosphorylation of signal transducers and activators of transcription 3 （p-STAT3）signal pathway in rats with precancerous lesions of gastric carcinoma （PLGC）. Methods Totally 96 Wistar rats were randomly divided into the blank control group （abbreviated as the blank group, n =16）and the model group （ n =80）. The PLGC rat model was established by complex pathogenic factors, in which methyI-N＇-nitro-N-nitrosoguanidine （MNNG）was mainly used. After successful modeling, 75 rats randomly selected were divided into the model group, the Vitacoenzyme group, the low dose XG group, the middle dose XG group, and the high dose XG group, 15 in each group. Fifteen rats were randomly selected from the blank group, and fed with ordinary standard forage and administered with 10 mL/kg 0.9% sodium chloride by gastrogavage. XG at 1. 254 g/kg, 2.508 g/kg, and 5.016 g/kg wasrespectively administered to rats in the three XG groups by gastrogavage. Rats in the model group were administered with 10 mL/kg 0.9% sodium chloride by gastrogavage. Vitacoenzyme was administered to rats in the Vitacoenzyme group. Vitacoenzyme Tablet was pulverized to prepare 0.1 g/mL 0.9% sodium chloride suspension and administered by gastrogavage. All the medication was performed once daily and continued for 12 weeks.The general conditions （including rats＇ fur, activity, food and water, excrement, body weight, and survival）, the pathological changes in the gastric mucosa, as well as the expressions of STAT3 and p-STAT3 were observed. Results Compared with the blank group,the expression levels of STAT3 and p-STAT3 increased in the model group （ P 〈0.05）. The general conditions, such as the activi- ty, food and water intake, and body weight were improved in each XG group. Compared with the model group, the expressions of STAT3 and p-STAT3 decreased in each XG group with statistical difference （ P 〈0.05）. The occurrence of PLGC, i.e., intestinal metaplasia （IM）and dysplasia （DYS） significantly de- creased with statistical difference （ P 〈0.05）. Compared with the Vitacoenzyme group, the occurrence of IM and DYS significantly decreased in the middle and high dose XG groups, showing statistical difference （P 〈0.05）. The expressions of STAT3 and p-STAT3 decreased more significantly in the middle and high dose XG groups, showing statistical difference （P 〈 0.05）. Conclusions XG could obviously improve the pathological conditions of gastric mucosa in rats with PLGC. It could fight against the progress of PL- GC by down-regulating the expressions of STAT3 mRNA and p-STAT3.