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目的:探讨他莫昔芬对小鼠腹主动脉瘤(AAA)的治疗作用及疗效的性别差异。方法:选择老年(60周龄)野生型C57BL/6小鼠,分3批进行实验,分别行单纯AAA造模(弹力蛋白酶诱导)、他莫昔芬预防性给药+AAA造模、AAA造模+他莫昔芬治疗;各批实验中的小鼠均雌雄各半,并设假手术对照,均于术后14 d取腹主动脉标本行相关指标检测。结果:第1批实验中雌雄鼠的AAA发生率均为100%。第2批实验中,雌鼠AAA的发生率明显低于雄鼠(30%vs.80%,P<0.05);血管的病理学改变明显轻于雄鼠,且雌鼠血管组织中雌激素受体α、过氧化氢酶水平明显高于雄鼠,而PCNA水平及炎症细胞及炎症因子水平明显低于雄鼠(均P<0.05)。第3批实验中,雌鼠AAA的发生率明显低于雄鼠(50%vs.100%,P<0.05);且雌鼠血管组织的病理改变、增殖反应、炎症反应均轻于雄鼠(均P<0.05)。结论:他莫昔芬对AAA的发生、发展方面有明显的抑制作用,但其作用有性别差异,表现为对雌鼠的AAA有较好的预防及治疗作用,对雄鼠有一定的预防作用而无治疗作用,机制可能与其对雌性动物有较强的雌激素受体诱导作用有关。
Objective: To investigate the effect of tamoxifen on the treatment of abdominal aortic aneurysm (AAA) in mice and its gender differences. Methods: Aged (60 weeks old) wild-type C57BL / 6 mice were selected and divided into three batches and were randomly divided into three groups: AAA model alone (elastase induction), prophylactic tamoxifen + AAA model, Mold + tamoxifen treatment; mice in each batch of experiments were male and female, and a sham control, were 14 days after surgery to take the relevant indicators of abdominal aortic specimens were detected. Results: In the first experiment, the incidence of AAA in both sexes was 100%. In the second experiment, the incidence of AAA in female rats was significantly lower than that in male rats (30% vs.80%, P <0.05); the pathological changes in blood vessels were significantly lighter than those in male rats, and estrogen in female rats Body α, catalase levels were significantly higher than male rats, and PCNA levels and inflammatory cells and inflammatory cytokines levels were significantly lower than the male rats (P <0.05). In the third experiment, the incidence of AAA in female rats was significantly lower than that in male rats (50% vs.100%, P <0.05). The pathological changes, proliferative responses and inflammatory responses in female rats were lighter than those in male rats All P <0.05). CONCLUSION: Tamoxifen has a significant inhibitory effect on the occurrence and development of AAA, but its effect is gender-differentiated, showing good preventive and therapeutic effects on AAA in female rats, and has some preventive effects on male rats Without treatment, the mechanism may be related to its strong female estrogen receptor induction.