诱导型一氧化氮合酶抑制剂对地鼠颊囊癌变的干预作用

Intervention Effect of an Inducible Nitric Oxide Synthase Inhibitor on Carcinogenesis of Hamster Cheek Pouch Carcinoma

目的 研究一氧化氮(NO)在肿瘤发生发展过程中所起的作用,探讨一氧化氮合酶(NOS)抑制剂对地鼠颊囊粘膜癌变所起的干预作用。方法 90只金黄地鼠分为实验1组(T1组)、实验2组(T2组)和空白对照组(C组),利用二甲基苯并蒽(DMBA)诱导T1、,12组地鼠颊囊癌变,并在T2组给予一氧化氮合酶抑制剂L硝基精氨酸甲酯(L-NAME),观察T1和12组颊囊黏膜癌变中病理改变,SABC免疫组化法检测iNOS、VECF、Ⅷ因子动态表达,硝酸还原酶法测定NO量的变化。结果 DMBA诱导T1组和T2组颊囊黏膜癌变率的差异有统计学意义,P<0.05,iNOS、VEGF阳性表达增加,NO量和微血管密度不断增加。结论 NO在地鼠颊囊癌的发生发展中起促进作用,而L-NAME起干预作用。

Objective To observe the expression changes of VEGF, iNOS and the level of MVD and NO during the evolution of Golden hamster cheek pouch carcinogenesis. To observe the pathological change during the evolution of Golden hamster cheek pouch carcinogenesis. To study the effect of NO in carcinogenesis in the pouch of hamster, and to investigate the effect of NOS in-hibiter L-NAME in interfering with carcinogenesis. Methods 90 golden hamsters were divided into three groups: 40 in experiment group, 40 in control group and 10 in blank group. DMBA was painted on hamster's cheek pouch in experiment and control group, L-NAME was given to hamster in experiment group at the dose of 0.02 ml/g. Hamsters were killed at 6,9,12 and 16 weeks, respectively. The blank group was killed at the 16 week. SABC immunohistochemistry assay was used to detect the expression of iNOS, VEGF and factorⅧ -related antigen. MVD was measured. The level of NO was measured by Spectrophotometry. Results The difference between control group and experiment group at the 12th week and 16th week was observed. The difference of positive expression rate of iNOS in all group was significant and difference between blank group and control group was significant, The difference of positive expression rate of VEGF in all group was significant and difference between blank group and control group at the 12 and 16 week was significant; there was significant difference in every group MVD from the 6 week control group to the 16th week control. There were significant difference among the control group, except the 6 week of experiment and control group. Conclusion There is an increased expression of iNOS and the level of NO, as well MVD during the evolution of Golden hamster cheek pouch carcinogenesis from slightly dysplasia to invasive carcinoma. NO plays an important role during the evolution of carcinogenesis, and iNOS inhibitor L-NAME can inhibit the carcinogenesis.