急性肝性脑病小鼠视觉功能障碍的机制研究  

Study on the mechanism of visual dysfunction and pathological changes in mice with acute hepatic encephalopathy

作　　者：李柯楠 拜云虎 王振华 倪子薇 朱昌磊 刘慧 杨雁灵 王亚云 LI Kenan;BAI Yunhu;WANG Zhenhua;NI Ziwei;ZHU Changlei;LIU Hui;YANG Yanling;WANG Yayun(Department of National Basic Medicine Teaching Demonstration Centre,School of Basic Medicine,Air Force Medical University,Xi’an 710032;Department of Hepatobiliary Surgery,Xijing Hospital,Air Force Medical University,Xi’an 710032;Department of Neurobiology,School of Medicine,Yan’an University,Yan’an 716000)

机构地区：[1]空军军医大学基础医学院国家级基础医学教学示范中心,西安710032 [2]空军军医大学第一附属医院肝胆外科,西安710032 [3]延安大学医学院神经生物学教研室,延安716000

出　　处：《神经解剖学杂志》2024年第5期533-540,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82201627,82000551);陕西省创新能力支撑计划(2023-CX-PT-334);陕西省自然科学基础研究计划(2022JQ-820);河南省联合共建项目(LHGJ20210804);西京医院医务人员技术提升项目(2023XJSY27);西京医院创新医学研究专项(XJZT24CY15)。

摘　　要：目的:研究急性肝性脑病(AHE)模型小鼠视觉功能变化及其机制。方法:将12只成年雄性C57BL/6J小鼠,随机分为实验组及对照组各6只,利用硫代乙酰胺(TAA)制备小鼠AHE模型,采用ELISA试剂盒检测小鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平;采用比色法检测血清氨水平;采用旷场实验及高架十字迷宫实验进行小鼠行为学检测;评估小鼠神经功能评分;采用苏木素-伊红(HE)染色进行小鼠肝脏及单眼(左眼)视网膜病理学检查;采用视觉电生理进行小鼠双眼视觉功能检测。采用逆行示踪腺相关病毒对c-Fos-Cre^(ERT2)小鼠丘脑腹外侧核(VL)进行标记。结果:与对照组相比较,AHE组小鼠肝功能指标异常并且出现神经功能改变;HE结果显示,肝脏组织出现明显肝细胞坏死、结构紊乱等改变;视网膜组织与对照组小鼠相比较无显著差异;视觉电生理结果显示,AHE小鼠双眼视觉功能改变(P<0.05);注射逆行示踪病毒结果显示,AHE模型激活的VL核团神经元主要接受来自同侧的视觉皮质神经元的传入投射。结论:TAA诱导的AHE小鼠视觉功能障碍主要为功能性改变,而非器质性改变,且与视觉皮质至VL通路激活有关。Objective:To study the changes in visual function and its mechanism in mice with acute hepatic encephalopathy(AHE)model.Method:Twelve male mice were divided into experimental and control groups,with six mice in each.A mouse model of AHE was created using TAA,and serum ALT,AST,and ammonia levels were measured using ELISA and colorimetric assays.Behavioral tests,including open-field and elevated cross maze experiments,were conducted,and neurological function scores were evaluated.HE staining was used to evaluate visual function scores in mice.Behavioural tests were conducted to assess neurological function scores.HE staining was used for pathological examination of the liver and retina.Visual electrophysiology was used to test visual function in both eyes.Retrograde tracer adeno-associated virus was used to label the ventrolateral thalamic nucleus(VL)of thalamus in c-Fos-Cre~(ERT2)mice.Results:Compared to the control group,the AHE mice had abnormal liver function and neurological changes.The HE results showed liver tissue damage.The retinal tissues were not significantly different from the control group.The visual electrophysiological results showed changes in visual function in both eyes of the AHE mice.The retrograde tracer virus injections revealed no significant difference in VL activation between the AHE model and the control group.In the AHE model,VL nucleus accumbens neurons primarily received input from ipsilateral visual cortical neurons.Conclusion:The visual deficits in AHE mice caused by TAA were primarily functional rather than organic changes,and were associated with the activation of the visual cortex-to-VL pathway.

关 键 词：急性肝性脑病 视网膜 视觉电生理 丘脑腹外侧核 视觉皮质 小鼠 

分 类 号：R575.3[医药卫生—消化系统]