摘要
目的:观察健脾活瘀方对胃癌前病变大鼠白介素6介导的Janus激酶/信号转导和转录激活因子(Janus kinase1/Signal transducer and activator of transcription 3,JAK1/STAT3)通路的影响,探讨该方干预胃癌前病变及阻断“炎-癌”转化的作用机制。方法:将48只雄性SD大鼠按随机数表随机分为正常组、模型组、替普瑞酮组和健脾活瘀方高、中、低剂量组,每组8只。除正常组外,其余各组均采用单功能烷化剂甲基硝基亚硝基胍(MNNG)、乙醇、雷尼替丁、0.9%氯化钠造模,造模时间为30周,各组采用相应药物治疗10周后处死大鼠。苏木精-伊红染色法(HE染色法)观察胃窦病理形态;酶联免疫吸附法(ELISA)法检测血清IL-6水平;聚合酶链反应(PCR)检测胃黏膜JAK1、STAT3 mRNA表达;蛋白免疫印迹法(Western blot)检测胃黏膜JAK1、STAT3、生存素(Survivin)、原癌基因(cancer-myc,c-Myc)、细胞因子信号转导抑制分子3(Suppressor of cytokine signaling,SOCS3)水平。结果:与正常组比较,模型组大鼠胃黏膜出现萎缩及异型增生改变,且JAK1 mRNA及STAT3 mRNA水平均增加(P<0.05);与模型组比较,健脾活瘀方高剂量组未见萎缩及异型增生,中剂量组及替普瑞酮组未见异型增生但有萎缩,低剂量组有轻度异型增生及萎缩,且各组的JAK1 mRNA水平较模型组降低(P<0.05),健脾活瘀方高、中剂量及替普瑞酮组的STAT3 mRNA水平降低(P<0.05);与替普瑞酮组比较,健脾活瘀方高剂量组的JAK1 mRNA及STAT3 mRNA表达水平无差异(P>0.05)。与正常组比较,模型组的IL-6、JAK1、STAT3、Survivin、c-Myc表达均显著增加(P<0.05),但SOCS3水平明显下降(P<0.05)。与模型组相比,健脾活瘀方高、中、低剂量组的JAK1、STAT3、Survivin、c-Myc蛋白表达显著下降(P<0.05),SOCS3蛋白表达明显上升(P<0.05);与替普瑞酮组相比,健脾活瘀方高、中剂量组JAK1、STAT3、Survivin、c-Myc、SOCS3蛋白含量无差异(P>0.05)。结论:健脾活瘀方能够干预胃癌前病变,具有阻断炎-癌转化的作用,其机制可能与其干预IL-6/JAK1/STAT3通路有关。
Objective:To investigate the effects of Jianpi Huoyu Formula on IL-6/JAK1/STAT3 signaling pathway in rats with precancerous lesions of gastric cancer(PLGC),and to explore the mechanism of intervening PLGC and blocking inflammation-cancer transformation.Methods:48 male SD rats were randomly divided into the normal group,the model group,Teprenone group and Jianpi Huoyu Formula groups of low-dose,medium-dose and high-dose,with 8 rats in each group.The medication intervention was 10 weeks.The changes in histopathology was observed by HE staining.The serum level of IL-6 was detected by ELISA method.The expressions of JAK1 mRNA and STAT3 mRNA in gastric mucosa were detected by real-time PCR.The levels of JAK1,STAT3,Survivin,c-Myc and SOCS3 in gastric mucosa were detected by Westernblot method.Results:Compared to the normal group,the gastric mucosa showed atrophy and dysplasia,the mRNA expressions of JAK1 and STAT3 were significantly increased in the model group(P<0.05).Compared to the model group,no atrophy and dysplasia were seen in the high-dose group of Jianpi Huoyu Formula;in the medium-dose group of Jianpi Huoyu Formula group and in Teprenone group,there was no dysplasia but atrophy;in the low-dose group of Jianpi Huoyu Formula,there were slight dysplasia and atrophy.Compared to the model group,the level of JAK1 mRNA was lower in all medication groups(P<0.05);the expression of STAT3 mRNA was decreased in the high-dose and medium-dose of Jianpi Huoyu Formula group and in Teprenone group(P<0.05).There were no statistical differences in the expressions of JAK1 mRNA and STAT3 mRNA between Teprenone group and the high-dose group of Jianpi Huoyu Formula(P>0.05).Compared to the normal group,the levels of IL-6,JAK1,STAT3,Survivin and c-Myc were significantly increased,and SOCS3 level was significantly decreased in the model group(P<0.05);which were significantly improved after the intervention of Jianpi Huoyu Formula and Teprenone(P<0.05);there were no statistical differences in the improvements between Teprenone group and Jianpi Huoyu Formula groups of medium-dose and high-dose(P>0.05).Conclusion:The mechanism of Jianpi Huoyu Formula in intervening PLGC and blocking inflammation-cancer transformation may be correlated to regulating IL-6/JAK1/STAT3 signal pathway.
作者
郭敏
王晓鸽
杨国红
曾震军
刘香丽
彭小利
张樾亚
GUO Min;WANG Xiaoge;YANG Guohong;ZENG Zhenjun;LIU Xiangli;PENG Xiaoli;ZHANG Yueya(The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中医药信息》
2020年第3期44-49,共6页
Information on Traditional Chinese Medicine
基金
河南省基础与前沿技术研究计划项目(162300410111)。
