三七总皂苷激活JNK信号通路对胃癌前病变大鼠胃黏膜组织的保护作用

Protective effect of panax notoginseng saponins on gastric mucosa of rats with gastric precancerous lesions through JNK signal pathway

目的:观察三七总皂苷对胃癌前病变(GPL)大鼠胃黏膜保护作用。方法:空白组常规饲养,造模组给予200μg/mL MNNG自由饮用+隔日禁食法复制GPL大鼠模型,MNNG造模16周后,将造模组随机分为模型组,三七总皂苷高剂量(300mg/kg)、低剂量(150mg/kg)组,连续灌胃给药10周后,观察各组胃黏膜组织结构;Western blot法检测ERK、p-JNK、JNK、p53、NF-κB、p-NF-κB、E-cad、Caspase3、Bcl-2、Bax蛋白表达。结果:三七总皂苷各剂量组大鼠胃黏膜呈粉红色,光泽度欠佳;胃黏膜上皮组织多见良性反应增生性改变,较模型组胃组织腺体排列相对整齐,腺体形态尚规则,少见"背靠背"或复层改变。与空白组比较,模型组大鼠胃黏膜JNK、p-JNK、Caspase3蛋白表达均显著降低(P<0.01,P<0.05),NF-κB、p-NF-κB、p53、E-cad蛋白表达及Bcl-2/Bax比值均显著上升(P<0.05,P<0.01);与模型组比较,两给药组大鼠胃黏膜JNK、p-JNK表达显著升高(P<0.01,P<0.05),E-cad表达显著降低(P<0.05),三七总皂苷高剂量组大鼠胃黏膜NF-κB、p53表达显著降低(P<0.05),三七总皂苷高、低剂量组大鼠胃黏膜Caspase3蛋白表达显著升高(P<0.05)。结论:三七总皂苷可通过诱导JNK信号通路的激活,诱导凋亡发生与抑制炎性反应延缓胃黏膜组织的恶性进展,保护胃黏膜。

Objective:To observe the protective effect of panax notoginseng saponins(PNS)on gastric mucosa of gastric precancerous lesions(GPL).Methods:In the control group,the rats were fed regularly,and MNNG+fasting every other day was given to the model group to copy the GPL model,after 16 th week of MNNG modeling,rats were randomly divided into model,PNS high-dose(300 mg/kg),PNS low-dose(150 mg/kg)groups.After successfully establishing the GPL model,the rats were consecutively administered PNS by gastro gavage for 10 weeks.Ultrastructure of gastric mucosa in each group was observed.Expressions of ERK,p-JNK,JNK,p53,NF-κB,p-NF-κB,E-cad,Caspase3,Bcl-2,Bax in gastric mucosa in all groups were tested by Western blot method.Results:By contrast to model group,intestinal metaplasia and dysplasia had an improvement in PNS.Interestingly,the scope of dysplastic gastric epithelial cells was decreased after treatment with PNS.Compared with the control group,protein expressions of NF-κB,p-NF-κB,p53,E-cad and the ratio of Bcl-2/Bax in the model group increased significantly(P<0.05,P<0.01),protein expressions of JNK,p-JNK,Caspase3 in the model group decreased significantly(P<0.01,P<0.05).Compared with the model group,protein expressions of JNK,p-JNK in the PNS two dose groups were evidently increased(P<0.01,P<0.05);protein expression of E-cad in the PNS two dose groups were remarkably increased(P<0.05);protein expression of NF-κB,p53 in the PNS high-dose group were evidently reduced(P<0.05);protein expression of Caspase3 in the PNS high,low-dose groups were remarkably increased(P<0.05).Conclusion:PNS can induce the activation of JNK signaling pathway,induce apoptosis and inhibit inflammatory response,delay the malignant progression of gastric mucosa,and protect the gastric mucosa.