优化复合应激方案成功构建模拟临床病因的胃功能障碍与抑郁共病模型OA
Establishment of an gastric dysfunction and depression comorbidity model simulating clinical etiology in mice using a combined stress protocol
目的 构建一种稳定可行的模拟临床发病的胃功能障碍与抑郁共病模型.方法 将30只C57BL/6J雄性小鼠随机分为对照组、模型14 d组、模型28 d组(n=10).模型组采用夹尾、冰生理盐水灌胃及不规则进食3种应激因素持续干预,对照组常规饲养.通过应力传感器记录胃动力、小动物活体成像评估胃排空、HE染色观察胃组织形态;旷场、高架十字迷宫、悬尾、强迫游泳和糖水偏好试验评价抑郁行为;ELISA检测血清中促肾上腺皮质激素释放因子(CRF)、脑源性神经营养因子(BDNF)、胃泌素(GAS)、胃动素(MTL)及胃组织中一氧化氮合酶(NOS)及乙酰胆碱酯酶(AchE)含量,分析共病发生的可能外周机制.结果 与对照组相比,模型14 d组小鼠体质量和进食量下降,胃运动振幅降低和胃排空延迟(P<0.05),但各抑郁行为学指标均未出现明显变化(P>0.05);模型28 d组小鼠体质量和进食量进一步下降、胃运动振幅降低和胃排空延迟加剧(P<0.01),同时出现小鼠旷场活动总距离及中央穿越时间和次数降低、进入开放臂次数和时间减少、悬尾与强迫游泳不动时间增加及糖水偏好下降等抑郁行为(P<0.01);与模型14 d组比较,模型28 d组体质量和进食量下降,胃运动振幅降低和胃排空延迟明显(P<0.01),各抑郁行为学指标均出现变化(P<0.01).ELISA结果显示,与对照组相比,模型14 d组血清BDNF降低和CRF升高(P<0.05),GAS和MTL减少,胃组织中NOS升高,AchE减少(P<0.01),模型28 d组小鼠血清CRF升高,BDNF、GAS、MTL减少,胃组织中NOS升高,AchE减少(P<0.01);与模型14 d比较,模型28 d组血清CRF升高,BDNF、MTL、GAS进一步降低(P<0.01),胃组织中NOS上升(P<0.05).HE染色显示,模型14、28 d组小鼠胃黏膜均未见器质性损伤.结论 通过夹尾、冰生理盐水灌胃及不规则禁食3种应激干预28 d,成功构建一种稳定易复制的胃功能障碍与抑郁共病的动物模型,血清神经递质、脑肠肽水平紊乱或迷走神经活性异常等可能是胃功能障碍与抑郁共病的外周机制.
Objective To establish a mouse model with the comorbidity of gastric dysfunction and depression mimicking clinical onset of the condition.Methods Thirty male C57BL/6J mice were randomly divided into control,14-day model,and 28-day model groups(n=10).The mice in the latter two groups were subjected to continuous combined stresses induced by tail clamping,cold-saline gavage and irregular feeding for 14 or 28 days.Gastric motility,gastric emptying and histopathological changes of the mice were evaluated using strain gauge sensors,in vivo imaging and HE staining,respectively,and behavioral tests were used to assess their depression-like behaviors.Serum corticotropin-releasing factor(CRF),brain-derived neurotrophic factor(BDNF),gastrin,motilin,and gastric nitric oxide synthase(NOS)and acetylcholinesterase(AChE)levels were measured by ELISA to explore the peripheral mechanisms.Results Compared with control mice,the mice in 14-day model group exhibited reduced body weight,food intake and gastric motility amplitude with delayed gastric emptying but showed no significant depression-like behaviors;in 28-day model group,these changes were further exacerbated,and significant depression-like behaviors were observed.Compared with 14-day model group,the 28-day model group displayed severer gastric dysfunction and depression-like behaviors.Compared with control group,exposure to complex stresses for 14 days significantly increased serum CRF and decreased BDNF,gastrin and motilin levels,increased gastric NOS and decreased gastric AChE level,which were worsened after a 28-day exposure.HE staining showed no obvious histological changes in the gastric mucosa in the two model groups.Conclusion Combined stresses induced by tail clamping,cold-saline gavage and irregular feeding for 28 days can induced the comorbidity of gastric dysfunction and depression in mice,and abnormal changes in serum neurotransmitters,brain-gut peptides and vagus activity may partly participate in the pathogenesis of the comorbidity.
黄清扬;沈雯雯;胡进;马宏坤;胡雁冰;张程杰;申国明;王浩
安徽中医药大学 中西医结合学院,安徽 合肥 230012安徽中医药大学 中西医结合学院,安徽 合肥 230012安徽中医药大学 中西医结合学院,安徽 合肥 230012安徽中医药大学 针灸推拿学院,安徽 合肥 230012安徽中医药大学 中西医结合学院,安徽 合肥 230012安徽中医药大学 中西医结合学院,安徽 合肥 230012安徽中医药大学 中西医结合学院,安徽 合肥 230012安徽中医药大学 中西医结合学院,安徽 合肥 230012||安徽中医药大学 经脉脏腑相关安徽省重点实验室,安徽 合肥 230012
胃功能障碍抑郁情绪动物模型复合应激胃动力行为学评价
gastric dysfunctiondepression-like behavioranimal modelcombined stressgastric motilitybehavioral assessment
《南方医科大学学报》 2026 (5)
1059-1065,7
安徽省自然科学基金(2408085MH223)安徽省高校优秀青年科研项目(2022AH030065)国家自然科学基金(82474224)经脉脏腑相关安徽省重点实验室开放课题(2024AHMVC04)Supported by National Natural Science Foundation of China(82474224).
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