美沙拉嗪干预溃疡性结肠炎相关癌变小鼠的实验研究

目的:观察美沙拉嗪防治溃疡性结肠炎相关癌变小鼠的实验研究。方法:60只清洁级Balb/c小鼠随机分5组,每组12只,正常组、模型组、低、中、高剂量治疗组;除外正常组,其余各组采用DMH/DSS复合法制备溃结癌变模型,模型组予等剂量生理盐水、治疗组分别予不同剂量美沙拉嗪干预9周。第9周末将全部小鼠脱椎处死,截取全部结肠(回盲部-肛门),肉眼及光镜下观察小鼠结肠组织形态学变化。结果:模型组小鼠结肠肉眼可见浆膜层散在、多处息肉状隆起变化,镜下见腺体萎缩、高级别上皮内瘤变,部分癌变;低剂量组肉眼见结肠黏膜充血水肿,部分可见溃疡样改变,镜下见黏膜充血肿胀,部分腺体萎缩;中、高剂量组肉眼见结肠黏膜充血、水肿,糜烂,镜下见黏膜上皮脱落,充血肿胀,未见溃疡及癌变,与模型组比较,有统计学意义(P0.05)。各剂量组之间比较,无统计学意义(P0.05)。结论:美沙拉嗪具有防治溃结相关癌变的生物学效应。

The intervention effect of Mesalazine on preventing ulcerative colitis associated carcinogenesis

Objective: The mechanism of Mesalazine preventing ulcerative colitis associated carcinogenesis(UCAC) was discussed by observing the changes of β-catenin and C-myc in colon mucosa.Methods: Sixty Balb/c rats were randomly divided into five groups: Normal group,Blank group,Intervention group(low dosage,mild dosage,high dosage).Each group has 12 rats.Except normal group,the other groups were intraperitoneal injected with 0.4% DMH 20mg/kg for two times a week.After intraperitoneal injection of DMH,those groups were given orally 3% DSS for two weeks.The above process was repeated three times.The blank group was treated with normal saline by intragastric administration for twenty weeks.Those intervention groups were treated with different dosage of Mesalazine by intragastric administration for twenty weeks.The colon histomorphology was assayed by naked eyes and light microscope.Result: There are changes of hyperemia and edema and polyps occupation in colon mucosa of blank group by naked eyes.Meanwhile,the changes of high-grade intraepithelial neoplasia and carcinogenesis were seen in blank group.Compared with intervention group,the difference is obvious(P<0.05).However,the histomorphology changes in low dosage intervention group is characterized by hyperaemia and ulcer and low-grade intraepithelial neoplasia.The histomorphology manifestiation in mild-high dosage groups are characterized by hyperaemia and edema.There is no significant difference in histomorphology manifestiation in intervention groups(P>0.05).Conclusion: Mesalazine may exert a distinct effect on preventing ulcerative colitis associated with carcinogenesis.