DON与NOC致病作用的实验流行病学研究

发布时间：2019-06-03 09:34

【摘要】： 目的:利用亚慢性动物实验观察脱氧雪腐镰刀菌烯醇(DON)、N-亚硝基化合物(NOC)对实验动物的致病作用,主要观察对动物消化系统的影响,探讨DON、NOC对实验动物食管、胃、肝脏、直肠组织急慢性损伤及其潜在的致癌作用,为消化系统肿瘤的病因预防提供理论依据。方法:以断乳7日的小鼠为实验对象,雌雄各半,随机分为四组,每组32只,其中DON组染毒剂量为DON 0.5mg/kg/次,NOC组染毒剂量为NOC 0.25mg/kg/次,DON+ NOC组染毒剂量为DON0.5mg/kg/次+NOC0.25mg/kg/次,染毒方式为隔日灌胃,对照组用等体积生理盐水灌胃。实验周期满60日后处死小鼠,取小鼠食管、胃、肝脏、直肠组织制作HE切片,观察各实验组、对照组食管、胃、肝脏、直肠组织癌前病变、急慢性损伤。此外,对泰安地区粮食样品中DON进行抽样检测,观察DON含量与肿瘤关系。利用SAS9.0统计软件对数据进行处理、分析。结果: 1.对食管组织的影响:实验组出现了乳头延长、上皮乳头状增生、上皮细胞空泡化、上皮增生角化不全改变,阳性率分别为:34.04%、8.51%、8.51%、20.21%;其中DON+NOC实验组乳头延长、上皮乳头状增生、上皮增生角化不全改变阳性率较高,分别为:50.00%、15.63%、25.00%;DON组乳头延长阳性率较高,为32.26%;NOC组乳头延长、上皮增生角化不全改变阳性率较高,分别为:19.35%、25.81%,对照组未出现上述改变。实验组乳头延长、上皮增生角化不全改变与对照组进行χ2检验,有统计学意义(P0.05)。 2.对胃组织的影响:实验组胃出现息肉形成趋势、腺体轻度异型、深层上皮轻度异型、黏膜上皮坏死、腺体坏死、上皮增生、脉管扩张等组织学改变,阳性率分别为:31.91%、29.79%、42.55%、40.43%、52.13%、13.83%、9.57%;其中DON+NOC实验组息肉形成趋势、深层上皮轻度异型、黏膜上皮坏死阳性率高,分别为:46.88%、62.50%、59.38%;DON组息肉形成趋势、腺体轻度异型、腺体坏死和黏膜上皮坏死阳性率较高,分别为:22.58%、29.03%、25.81%和45.16%;NOC组深层上皮轻度异型、黏膜上皮坏死和腺体坏死阳性率较高,分别为:38.71%、51.61%和52.61%;各组均有炎症性改变。实验组小鼠出现的胃息肉形成趋势、胃腺体轻度异型、深层上皮轻度异型、腺体坏死和黏膜上皮坏死改变与对照组进行χ2检验,有统计学意义(P0.05),DON+NOC组与DON组的深层上皮轻度异型出现率进行四格表χ2检验,有统计学意义(P0.007)。 3.对肝脏组织的影响:实验组肝脏出现大片坏死、大片脂肪变性、小片脂肪变性、灶性坏死、嗜酸性变、小灶区异型、炎细胞浸润、双核肝细胞、脉管扩张病变,阳性率分别为:7.45%、39.36%、22.34%、13.83%、17.02%、17.02%、76.60%、50.00%、31.91%;其中DON+NOC组组织大片坏死、大片脂肪变性、灶性坏死、双核肝细胞和灶区异型阳性率高,分别为:21.88%、65.63%、28.13%、25.00%和25.00%;DON组大片脂肪变性和小灶区异型阳性率较高,分别为:22.58%和25.81%;NOC组大片脂肪变性和脉管扩张阳性率较高,分别为:29.03%和25.58%;对照组肝脏组织出现了脉管扩张、小片脂肪变性、炎细胞浸润、嗜酸性变改变,阳性率分别为:6.25%、75.00%、45.45%、33.33%。实验组肝脏出现大片坏死、大片脂肪变性、灶性坏死、小灶区异型、双核肝细胞、脉管扩张各病变与对照组进行χ2检验,均有统计学意义(P0.05),DON+NOC组分别与DON组、NOC组出现的大片脂肪变性进行四格表χ2检验,有统计学意义(P0.007)。 4.对直肠组织的影响:实验组出现腺体轻度异型、黏膜上皮坏死、固有膜炎细胞、黏膜水肿、腺体结构紊乱、淋巴滤泡形成、嗜酸粒细胞等改变,阳性率分别为:40.43%、43.62%、79.79%、58.51%、14.89%、8.51%、23.40%;其中DON+NOC组腺体轻度异型、黏膜上皮坏死和腺体结构紊乱阳性率高,分别为:71.88%、46.88%和18.75%;DON组腺体轻度异型、黏膜上皮坏死阳性率较高,分别为:29.03%、32.26%;NOC组腺体轻度异型、黏膜上皮坏死和腺体结构紊乱阳性率较高,分别为:19.35%、51.61%和16.13%;对照组组织出现了炎症水肿、淋巴滤泡和嗜酸粒细胞浸润改变,阳性率分别为:25.00%、3.13%、3.13%。实验组小鼠直肠组织出现腺体轻度异型、黏膜上皮坏死脱落、腺体结构紊乱、嗜酸粒细胞、固有膜炎细胞改变与对照组进行χ2检验,有统计学意义(P0.05),DON+NOC组分别与DON组、NOC组出现的直肠腺体轻度异型进行四格表χ2检验,有统计学意义(P0.007)。 5.泰安市食管癌高发区小麦面、玉米面样品中DON含量与低发区进行t检验,有统计学意义(p0.05)。结论: 1.DON可诱发消化系统出现组织坏死、炎性水肿、大片脂肪变性等急慢性病理损伤和息肉形成趋势、腺体上皮异型增生等癌前病变。 2.NOC可引起实验动物出现组织坏死、水肿变性、脂肪变性等急慢性病理损伤和息肉形成趋势、腺体上皮轻度异型、食管乳头延长等癌前病变。 3.DON+NOC组实验动物出现消化系统组织坏死、脂肪变性、炎性水肿等急慢性病理损伤,导致息肉形成趋势和腺体、上皮异型增生等癌前病变,且病变程度强于DON、NOC单独作用。 4.泰安地区食管癌高发区粮食样品中DON含量高于低发区。 5.实验结果表明:DON、NOC对消化系统具有明显的损伤,同时具有潜在的致癌效应,且二者间存在协同作用。
[Abstract]:Objective: To observe the effect of deoxynivalenol (DON) and N-nitroso compound (NOC) on the animal's digestive system by subchronic animal experiment, and to observe the effect of DON and NOC on the experimental animal's esophagus, stomach and liver. Rectal tissue has acute and chronic injury and its potential carcinogenic effect, and provides a theoretical basis for the prevention of the cause of the digestive system tumor. Methods: The experimental subjects were divided into four groups, each group of 32 rats were divided into four groups. The dosage of DON group was DON 0.5 mg/ kg/ day, and the exposure dose of the NOC group was about 0.25 mg/ kg/ day, and the exposure dose of DON + NOC group was DON0.5 mg/ kg/ time + NOC0.25 mg/ kg/ day, and the exposure mode was the next day. Gavage, control group, and other volume of physiological saline The mice were sacrificed at 60 days after the experiment. The HE sections were made from the esophagus, the stomach, the liver and the rectum of the mice. The experimental groups, the control group, the esophagus, the stomach, the liver, the rectum, the precancerous lesions, and the acute and chronic diseases were observed. Damage. In addition, DON was sampled and tested in the food samples in the Taian area to observe the DON content and the tumor. the data is processed by using the SAS9.0 statistical software, Analysis. Results:1. The effect of 1.1 on the tissue of the esophagus: The experimental group showed the changes of the papilla, the hyperplasia of the epithelium, the vacuolation of the epithelial cells, and the hyperkeratosis of the epithelium. The positive rate was 34.04%, 8.51%, 8.51% and 20.21%, respectively. The positive rate of nipple extension, epithelial papillary hyperplasia and epithelial hyperplasia of the experimental group was 50.00%, 15.63% and 25.00%, respectively. The positive rate of nipple extension in the DON group was higher, which was 32.26%. The papilla of the NOC group was prolonged, and the positive rate of the epithelial hyperplasia was higher, respectively: 19.35 %, 25.81%, control The above-mentioned changes were not observed in the group. In the experimental group, the nipple extension and the changes of the epithelial hyperplasia and the control group were compared with the control group. (P0.05).2. The effect of the gastric tissue: the tendency of the formation of the polyp in the stomach of the experimental group, the slight dysplasia of the gland, the mild dysplasia of the deep epithelium, the epithelial necrosis of the mucous membrane, the necrosis of the gland, the hyperplasia of the epithelium, the expansion of the vessel, etc. The positive rate was 31.91%, 29.79%, 42.55%,40, respectively. 43%, 52.13%, 13.83%, 9.57%, among which, the positive rate of polypus in the experimental group of DON + NOC was 46.88%, 62.50% and 59.38%, respectively. The positive rate of necrosis was: 22.58%, 29.03%, 25.81% and 45.16%, respectively. The positive rate of the deep epithelium of the NOC group was higher than that of the epithelial necrosis and the glandular necrosis. The positive rate was 38.71%, 51.61% and 52.61, respectively. %; there were inflammatory changes in each group. The tendency of the formation of the gastric polyps in the experimental group, the mild dysplasia of the stomach gland, the mild dysplasia of the deep epithelium, the change of the glandular necrosis and the change of the epithelial necrosis of the mucous membrane were carried out in the control group. The occurrence rate of deep epithelium of DON + NOC and DON group was examined by four-grid-2 test, and the statistical significance was statistically significant (P0.05). Study significance (P.007).3. The effect of liver tissue: a large area of necrosis in the liver of the experimental group, large amount of fat degeneration, small die-fat degeneration, focal necrosis, eosinophilic transformation, small-range heterotype, inflammatory cell infiltration, dual-core liver cell and vascular expansion, the positive rate was 7.45%, respectively. , 39.36%, 22.34%, 13.83%, 17.02%, 17.02%, 76.60%, 50.00%, 31.91%, among which, large areas of necrosis, large area of fat degeneration, focal necrosis, dual-core liver and range were high in DON + NOC group, respectively: 21.88%, 65.63%, 28.13%, respectively. 25.00% and 25.00% in DON group. The positive rate of heterotypic positive rate in large area of DON group was 22.58% and 25.81%, respectively. The positive rate of large amount of fat degeneration and vessel expansion in the NOC group was 29.03% and 25.58%, respectively. The positive rate was 6.25% and 75.00%, respectively. 45.45%, 33.33%. The liver of the experimental group had a large area of necrosis, large area of fat degeneration, focal necrosis, small-range special-shaped, dual-core liver cell, vessel-expanding each lesion and the control group for 2-test, all had statistical significance (P0.05), D. and the on + noc group is respectively connected with the don group and a large amount of fat denaturation which occurs in the noc group is subjected to a four-cell table-2 test, There was a statistical significance (P.007).4. The effect of the rectum on the rectal tissue: the experimental group had the changes of the gland, the epithelial necrosis of the mucous membrane, the intrinsic mucositis, the edema of the mucous membrane, the disorder of the gland, the formation of the lymphoid follicle, the eosinophil, etc. The positive rate was 40.43%, 43.62%, 79.79%,58, respectively. 5.51%, 14.89%, 8.51%, 23.40%, among which, the positive rate of the gland in the gland of the DON + NOC group was 71.88%, 46.88% and 18.75%, respectively, and the positive rate of the mucosal epithelia was higher in the DON group and 29.03%, respectively. The positive rates of inflammatory edema, lymphoid follicles and eosinophil infiltration in the control group were 2.26%, 51.61% and 16.13%, respectively. In the experimental group, the rectal tissues of the experimental group had a slight abnormal gland, the epithelial necrosis of the mucous membrane, the disorder of the glandular structure, the eosinophil, the change of the intrinsic mucositis and the control group, and there was a statistical significance (P0.05). ), the DON + NOC group and the DON group and the NOCs group had a four-cell table of the mild dysplasia of the rectal gland, which was found in the NOC group. The content of DON and the low-yield of the wheat flour and the corn flour in the high-hair region of the esophageal cancer in Taian 'an city were statistically significant (P.007). area Conclusion:1. DON can induce tissue necrosis, inflammatory edema and large amount of fat degeneration in the digestive system. 2. NOC can cause acute and chronic pathological changes such as tissue necrosis, edema, and fatty degeneration in the experimental animals. 3. The experimental animals of the DON + NOC group showed acute and chronic pathological changes of the digestive system, such as the necrosis of the digestive system, the degeneration of the fat, and the inflammatory edema, leading to the tendency of the polyp to form and the gland. Precancerous lesions such as body and epithelial dysplasia, and the degree of lesion is stronger than DON, NOC 4. The DON content in the high-hair region of the esophageal cancer in the Taian region was higher than that of the low-yield region.
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R181.3

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