雌二醇对二甲肼诱发的大鼠结肠隐窝异常的影响

Effect of estrogen on 1, 2-dimethyihydrazine-induced crypt fission of rat colon

目的在应用二甲肼（DMH）诱导大鼠结肠癌的模型上观察雌激素对结肠黏膜隐窝分裂、隐窝变异及隐窝上皮增殖状况的影响。方法将30只雌性大鼠分为假手术和卵巢切除后DMH处理，卵巢切除术加DMH的同时给予雌二醇处理或溶剂处理，及假手术加溶剂处理共5组，8周后检测各指标。结果DMH处理后异形隐窝灶（ACF）总数量及大ACF数量[异常隐窝内隐窝数（AC）〉6个]明显升高（57．80±6．54，P〈0．01；9．00±3．16，P〈0．01），隐窝分裂指数明显升高（17．60±4．93，P〈0．01），隐窝分裂指数与正常隐窝体积及异常隐窝的AC值正相关，而与正常隐窝增殖细胞核抗原（PCNA）表达水平不一致。卵巢切除后DMH的作用更明显，而卵巢切除后补充雌激素可以抵消卵巢切除的作用。结论雌激素可影响DMH诱导的ACF，其机制与影响结隐窝分裂相关。

Objective To investigate the effects of 1, 2-dimethylhydrazine （DMH） and estrogen on colonic crypt fission and aberrant crypt foci （ACF） formation. Methods Thirty female 4-months-old Sprague-Dawley rats were divided into five groups. Group A was the blank control, which was treated with vehicle injection after a sham operation; group B was treated with DMH after sham operation; group C was ovariectomized and treated with vehicle injection; group D was ovariectomized and treated with DMH injec- tion; and group E was ovariectomized and injected with both DMH and estradiol. The rats were sacrificed after 8 weeks of chemical treatment. The colonic ACF formation, crypt fission, crypt volume and crypt pro- liferating cell nuclear antigen （PCNA） expression were analyzed. Results The number of total ACF and the ACF with AC （〉6） in group D were larger than group B （57.80±6. 54 vs. 29. 67±6. 15 ,P 〈0. 01, 9.00 ±3.16 vs. 2.83±1.33,P〈0.01） andgroupE （38. 40 ±4. 22,P 〈0.01,4.40±l.34,P〈0.01）. Crypt fission index in group D was larger than group B [ （ 17.60 ± 4. 93 ） % vs. （ 1.50 ± 1.05 ） %, P 〈 0. O1 ] and group E [ （ 1.40± O. 55 ） %, P 〈 0. O1 ]. The PCNA index in group D was much larger than group A （P 〈 0. O1 ）, group B （ P 〈 O. O1 ）, and group C （ P 〈 0. O1 ）, and smaller than group E （ P 〈 O. 01 ）. The crypt volume was increased exclusively in group D （P 〈 O. 01 ）. There was an evident correla- tion （P 〈 0. 05） between the high crypt fission index and high amount of large ACF. The crypt fission was correlated to the crypt volume instead of the crypt cell PCNA expression. Conclusion DMH promoted the ACF formation and development, and also promoted the crypt fission. Ovariectomy alone had no similar effect, but it could exaggerate, while estradiol replacement could inhibit the DMH-induced elevation of crypt fission index and ACF development. These results suggested that the influence on crypt fission might be involved in the carcinogenetic effects of DMH and protective effect of estrogen on rat colon. And the mechanism underlying the crypt fission acceleration might be more complicated than promotion of crypt cell proliferation.