大鼠胃癌前病变模型的建立

目的:采用含马兜铃酸中药关木通建立一种大鼠胃黏膜癌前病变模型。方法:将SD大鼠按体重随机分为对照组和关木通乙醇提取物不同剂量组(以马兜铃酸Ⅰ计分别为2.5,5,10 mg.kg-1)。各组隔日灌胃给予1次。分别于给药后第10,15,20周,分批从每组抽取部分动物处死,解剖,称量胃质量,折算胃指数和胃肿瘤质量。将胃固定于4%中性甲醛溶液中,常规进行石蜡包埋、切片、HE染色,光学显微镜下观察胃组织形态学改变,记录各组发生胃黏膜良性增生、胃黏膜癌前病变(Ⅰ,Ⅱ,Ⅲ度不典型增生)和恶性胃癌发生的动物数。结果:大鼠灌胃给予关木通提取物(分别相当于马兜铃酸Ⅰ2.5,5.0,10.0 mg.kg-1)10周时,各剂量组可见前胃黏膜乳头状瘤增生。随造模时间延长,乳头状瘤数量增多。相当于马兜铃酸Ⅰ5.0,10.0 mg.kg-1剂量组造模10周时,即可见胃癌前病变,阳性率较高。造模15周时,相当于马兜铃酸Ⅰ5.0 mg.kg-1及其以上剂量组的胃癌前病变发生率高达100%。造模20周时,可见多数动物发生胃癌。结合动物耐受情况、胃黏膜癌前病变发生率以及肿瘤发展情况,认为相当于马兜铃酸Ⅰ5.0 mg.kg-1的剂量为最适宜造模剂量,癌前病变阶段为造模10～15周。结论:大鼠灌胃给予含马兜铃酸中药关木通提取物可以在较短时间内形成理想的胃癌前病变模型。

Development of gastric precancerous lesion animal model

Objective: To establish a model of gastric precancerous lesion by using Aristolochic manshuriensis which contains aristolochic acids.Method: The SD rats were randomly divided into four groups: control and three different doses of ethanol extractive of A.manshuriensis(EEA)(corresponding to aristolochic acid Ⅰ 2.5,5.0,10.0 mg·kg-1),respectively.EEA was intragastrically given to rats every other day.At the end of the 10th,15th,20th week,part of the rats in each group was sacrificed and the stomachs were weighed.The gastric tumor was assessed by the weight and the relative stomach weight to the body weight.The stomachs were fixed in 4% neutral formalin,and the paraffin imbedding tissues were sliced and HE stained.Histomorphology was observed under the light microscope to determine gastric hyperplasia,mucosa precancerosis(atypical hyperplasia) and gastric cancer formation.Result: The rats treated with different doses of EEA for 10 weeks induced mucosa papillary,epithelioma hyperplasia.Histological observation showed mucosa precancerosis lesions characterized as atypical hyperplasia at the dose levels corresponding to aristolochic acid Ⅰ 5.0 and 10.0 mg·kg-1 treated for 10 weeks.The incidence rate of gastric precancerosis in those two groups was 100% at the 15th week.Malignant tumors were observed in most of the animals in 10.0 mg·kg-1 group.The animals in 5.0 mg·kg-1 group were well tolerant compared to 10.0 mg·kg-1 group during the course of experiment,so the dose of aristolochic acid I 5.0 mg·kg-1 and 10-15 weeks treatment were considered to be optimum to establish the model of gastric precancerosis.Conclusion: A rat model of gastric precancerosis can be induced within a short duration by giving an oral administration of the ethanol extract of A.manshuriensis which contains aristolochic acids.