芪龙方防治MNNG诱发的大鼠胃癌及对病变胃基因表达的影响  

Prevention and Treatment of N-Methyl N'-Nitro-N-Nitrosoguanidine Induced Gastric Carcinoma and Inhibition of Gastric Oncogene Expression in Rat by Qilong Recipe

作　　者：施波[1] 陈飞松[2] 傅招娣[1] 刘晋生[2] 任蜀兵[2] 曹西华[1] 危北海[2] 

机构地区：[1]中国医学科学院药物研究所,北京100050 [2]北京市中医研究所

出　　处：《中国中西医结合杂志》2001年第S1期111-113,共3页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金(No.39500188);北京市科技新星计划(No.854871300)资助

摘　　要：目的:研究芪龙方对胃癌癌前疾病/胃癌的防治作用及芪龙方对病变胃粘膜 p53,c-myc,H-ras等基因表达的影响,以期从分子水平解释该药物的作用机理。方法:取新生3天的 Wistar 大鼠60只,随机分为5组,每组12只。每天每只用N。甲基-N-硝基-N-亚硝基胍(MNNG)溶液40μg/0.1ml 灌胃,连续10天。药物高、中、低治疗组每只分别灌服芪龙方液0.1g/0.1 ml、0.05 g/0.1 ml、0.025 g/0.1 ml。阳性对照组灌服增生平液每只0.05 g/0.1 ml,以上各组均每天1次。至第21天断乳后,阴性对照组动物灌服生理盐水10ml/kg 体重,药物高、中、低剂量组分别灌服芪龙方液10 g/kg、5 g/kg、2.5 g/kg 体重。阳性对照组灌服增生平液5 g/kg 体重,均每天1次,连续给药24周,至第56周末处死动物,胃标本常规石蜡包埋、切片,苏木素-伊红(HE)染色。对 p53,c-myc,H-ras 基因斑点杂交。结果:阴性对照组胃组织肉眼即见肿瘤。光镜下发现95%标本有萎缩性胃炎或伴胃粘膜异型增生,38%的标本发现胃腺瘤或胃腺癌。芪龙方各剂量能显著降低MNNG 诱发的大鼠胃粘膜异型增生、胃腺癌和腺胃癌的发生率(与阴性对照组比较,P<0.05),尤其是芪龙方高剂量组,未发现有腺瘤或胃癌,呈现较好的剂量效应关系。芪龙方各剂量组病变胃 p53、c-myc、H-ras 基因表达较阴性对照组均明显下降,且有明显的剂量效应关系。并且基因表达的降低与大鼠胃癌发生率减少相一致。结论:芪龙方对 MNNG 诱发的大鼠胃癌胃有较好的防治作用及对 p53,c-myc、H-ras 基因表达与胃癌发生率呈正相关。芪龙方用药后上述癌基因表达受到抑制、胃癌发生率下降,随用药剂量增加,癌基因的表达量明显下降。这从分子水平部分解释了癌基因表达与胃癌发生的关系以及芪龙方的作用机理。To study the effects of Qilong Recipe(QLR)in prevention and treatment of gastric precancerosis/cancer and on gene expression of p53,c-myc,H-ras,to elucidate the therapeutic mechanism in molecular level.Methods:Sixty Wistar rats,3 days old,were randomly divided into 5 groups:The high,middle and low dose QLR treated groups(Group A,B and C)were injected by N-methyl N'- nitro-N-nitrosoguanidine(MNNG)0.4 mg once daily for 10 successive days to induce gastric cancer,and also given QLR 10 g/kg,5 g/ kg and 2.5 g/kg respectively;the positive control group(Group D)was treated the same as above but with Zengshengping Liquid(增生 平液)5 g/kg instead of QLR,while the negative control group(Group E)was treated with normal saline only.The animals were killed 56 weeks after and their stomach was taken for detection of p53,c-myc and H-ras gene expression.Results:Tumor in stomach was found by gross inspection in Group E,under light microscopy,95% samples showed atrophic gastritis or accompanied with allotype pro- liferation of gastric mucous membrane,38% had adenoma or adenocarcinoma.QLR,in various doses could significantly decrease the oc- currence of MNNG induced allotype proliferation,adenoma or adenocarcinoma,as compared with those in Group E,the difference was significant,especially in Group A,no adenoma or adenocarcinoma was found,the tumor inhibitory effect was dose-dependent.Also,the p53,c-myc and H-ras gene expression in the QLR treated groups were lowered in dose-dependent manner and in accordance with the decrease in gastric carcinogenesis rate.Conclusion:QLR has good preventive and therapeutic effect on MNNG induced gastric cancer in rats,its effects on p53,c-mye and H-ras gene expression is positively correlated with the occurrenee of gastric cancer.These facts could be used to elucidate the relationship between cancer gene expression and carcinogenesis as well as the therapeutic mechanism of QLR from molecular level.

关 键 词：芪龙方 胃癌 癌基因 

分 类 号：R285.5[医药卫生—中药学]