苦参碱对乙基硝基亚硝基胍诱导大鼠胃癌的化学预防作用

Chemical preventive effect of matrine on ethyl nitrate nitroguanidine nitrate induced gastric cancer in rats

目的探讨苦参碱对乙基硝基亚硝基胍诱导大鼠胃癌的化学预防作用。方法选取雄性Wistar大鼠100只,随机分成4组,分别饮用不同的药物。其中阴性对照组(A组)25只,自由饮用纯净水;胃癌模型组(B组)25只,予以乙基硝基亚硝基胍(ENNG)1.5 mg/(只·d);实验组(C组)胃癌模型大鼠25只,予以注射用苦参碱150 mg/(kg·d)和乙基硝基亚硝基胍1.5 mg/(只·d);对照组(D组)阴性大鼠25只,予注射用苦参碱150 mg/(kg·d)。饲养24周后处死大鼠,肉眼和显微镜下观察各组大鼠胃黏膜改变情况,并检测胃组织增殖细胞核抗原(PCNA)、血清转化生长因子β1(TGF-β1)和B细胞淋巴瘤/白血病-2(Bcl-2)水平。结果 B组大鼠胃黏膜癌变率64.00%(16/25)明显高于C组胃黏膜癌变率12.00%(3/25),差异有统计学意义(P<0.05);C组大鼠PCNA、TGF-β1和Bcl-2水平明显低于B组,差异有统计学意义(P<0.05);饲养24周后B组大鼠胃黏膜萎缩、异型增生等改变率明显高于C组,差异有统计学意义(P<0.05);饲养24周后,A、D 2组大鼠胃黏膜均未发生癌变,胃黏膜萎缩、异型增生等改变无明显差异,差异无统计学意义。结论苦参碱能够通过降低PCNA、TGF-β1和Bcl-2水平抑制ENNG诱导大鼠胃癌发生,为苦参碱对人类胃癌潜在的化学预防作用提供了理论基础。

Objective To investigate the chemical preventive effect of matrine on ethyl nitrate nitroguanidine nitrate induced gastric cancer in rats. Methods 100 male Wistar rats were selected and randomly divided into four groups,each had 25 rats ,treated with different drugs respectively.Rats in the negative control group (group A)freely drunk water;each rat in gastric carcer model group (group B)drunk ethyl nitrate nitroguanidine nitrate (ENNG)1.5 mg/d by themselves;gastric cancer model rats of experimental group (group C)drunk matrine 150 mg/(kg · d)ethyl nitrate nitroguanidine nitrate (ENNG)150mg/(kg·d)by themselves;negative control group (group D)rats drunk matrine for injection 150 mg/(kg·d)by themselves.Rats were killed after 24 weeks,rats were observed on gastric mucosa change by naked eye and microscope ,and detected proliferating cell nucleus antigen (PCNA)of stomach tissue ,levels of serum transforming growth factorβ1 (TGF-β1 )and B cell lymphoma/leukemia-2 (Bcl-2).Results Canceration rate [64.00% (16/25)]of the rat gastric mucosa in Group B was significantly higher than that in group C [12.00% (3/25)],and the difference was statistically significant (P<0.05 );PCNA,TGF-β1 and the Bcl-2 level of rats in group C was lower than those in group B,and the difference was statistically significant (P<0.05 );after raising 24 weeks,change rate of gastric mucosa atrophy and hyperplasia in group B were significantly higher than those of group C,and the difference was statistically significant (P<0.05 );after raising 24 weeks,there was no cancerous changes on gastric mucosa in group A and D ,and the change of gastric mucosa atrophy and hyperplasia had no obvious difference,there was no statistically significant difference.Conclusion Matrine could inhibit rat gastric cancer induced by ENNG by lowering PCNA,TGF-β1 and the Bcl-2 levels,which provides evidence for the potential chemical preventive effect on human gastric cancer.