儿茶酚雌激素介导慢性间歇低氧诱导OSAHS雌性大鼠遗尿模型的建立

Catechol estrogen mediates chronic intermittent hypoxia induced OSAHS enuretic model in female rats

目的:利用慢性间歇低氧(CIH)诱导建立阻塞性睡眠呼吸暂停低通气综合征(OSAHS)遗尿雌性大鼠模型,并探讨儿茶酚雌激素(CE)在CIH诱导的OSAHS遗尿中的作用。方法:选取6周龄SD雌性大鼠16只,随机分成CIH组和对照组,每组8只。实验组置于常压间歇低氧舱,对照组置于同等条件下的空气模拟对照舱,均放置4周。监测24h进水及排尿量;测定血清中CE,儿茶酚胺类化合物如肾上腺素(Adr)、去甲肾上腺素(NA)和多巴胺(DA)含量及其儿茶酚氧位甲基转移酶(COMT)活性;测定排尿阈;留取膀胱行HE及Weigert染色,光镜下观察组织学变化。结果:CIH组大鼠氧舱外进水量及排尿量与对照组比,差异无统计学意义(P>0.05)。但CIH组大鼠氧舱内排尿量明显增加,血清中CE、Adr、NA和DA含量明显增高,而COMT的活性明显降低,排尿阈明显降低,膀胱组织光镜下显示膀胱逼尿肌肌束排列紊乱、疏松,部分肌束断裂。结论:CIH可诱导雌性大鼠发生遗尿,伴有排尿量增多,排尿阈降低,血清中儿茶酚胺类化合物含量增高,而COMT的活性降低,与儿童OSAHS诱发遗尿的临床症状相似,提示通过CIH诱导建立OSAHS遗尿雌鼠模型基本可行。

Objective: To establish obstructive sleep apnea and hypopnea syndrome (OSAHS) enuretic model induced by chronic intermittent hypoxia (CIH) exposure in female rat,and to explore the role of catechol estrogen (CE) in CIH induced OSAHS enuretic model.Methods: Sixteen Sprague-Dawley (SD) female rats (6 weeks old) were randomly divided into CIH group and the control group,with eight rats for each group.The CIH group was exposed to chronic intermittent hypoxia cabin for 4 weeks; meanwhile,the control group was exposed to normal air cabin.Water intake and urine output were recorded; the levels of CE,NA,Adr and DA in serum and the activity of COMT were measured,and threshold pressure was measured; bladder was taken for HE and Weigert staining,then the histological changes under light microscope were observed.Results: Compared with the control group,the water intake and urine output outside the cabin in CIH group had no significant difference.However,there was significant increase of urine output inside cabin in CIH group.Furthermore,the levels of CE,NA,Adr and DA in serum were significantly higher,whereas the activity of COMT and the threshold pressure were significantly decreased compared with that in the control group.HE staining showed the disordered arrangement of bladder detrusor muscle bundle and some breaking muscle bundles.Conclusion: CIH induces enuresis in female rats accompanying with increased urine output and CE,NA,Adr and DA levels in serum,decreased activity of COMT and threshold pressure,which are similar to the clinical characteristics in enuresis children.It suggests that it is feasible to use CIH to establish OSAHS enuretic female rat model.