醛缩酶 B 在果糖耐受与血糖稳态中的作用研究  

Role of aldolase B in fructose tolerance and glucose homeostasis in mice

作　　者：冯滢樱 史亚男[1] 麻献华 陈玉霞 章卫平 FENG Ying-ying;SHI Ya-nan;MA Xian-hua;CHEN Yu-xia;ZHANG Wei-ping(NHC Key Laboratory of Hormones and Development,Tianjin Institute of Endocrinology and Chu Hsien-I Memorial Hospital,Tianjin Medical University,Tianjin 300134,China;Department of Pathophysiology,Naval Medical University,Shanghai 200433,China)

机构地区：[1]天津医科大学朱宪彝纪念医院,天津市内分泌研究所,国家卫健委激素与发育重点实验室,天津市代谢性疾病重点实验室,天津300134 [2]海军军医大学病理生理学教研室,上海200433

出　　处：《中国病理生理杂志》2022年第6期1040-1045,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金重大研究计划(No.91857203)。

摘　　要：目的:建立全身性醛缩酶B(aldolase B,Aldob)基因敲除小鼠模型,探讨Aldob基因缺陷对小鼠果糖耐受和血糖稳态的影响。方法:利用敲除优先策略和胚胎干细胞基因打靶技术,建立全身性Aldob基因敲除小鼠模型,并通过Western blot验证敲除效果;监测普食喂养小鼠生长发育过程中的体重、体长、血糖和血脂水平;检测果糖灌胃前后小鼠血糖及血浆天冬氨酸转氨酶(aspartate aminotransferase,AST)和丙氨酸转氨酶(alanine aminotransferase,ALT)水平,取材分析肝、肾等器官的大小及形态学变化。结果:Aldob缺陷小鼠普食喂养时出现生长迟滞和低血糖;果糖灌胃后血糖呈降低趋势,血浆AST和ALT水平升高,并伴有肝肾肿大和肝脏病理性损伤。结论:Aldob在维持小鼠生长、血糖稳态和果糖耐受性中发挥重要作用。AIM:To generate a mouse model of global aldolase B(Aldob)gene knockout,and to examine its phenotypes of glucose homeostasis and fructose tolerance.METHODS:The knockout-first gene targeting strategy was used to generate Aldob gene knockout mice,and the deletion efficiency was verified by Western blot.The chow-fed mice were dynamically monitored for the body weight and blood glucose level.After fructose challenge by gavage,the changes of blood glucose and plasma aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were biochemi⁃cally analyzed,and the liver and kidney were examined for the mass and morphological alterations.RESULTS:The Aldob knockout mice showed a complete loss of Aldob protein in the liver and jejunum,and exhibited severe growth retardation and hypoglycemia on chow diet.Adult Aldob-null mice were intolerant to fructose challenge,as manifested by decreased blood glucose level as well as elevated plasma AST and ALT levels,and even lethality.The mutant mice had enlarged liver and kidney as well as overt liver injury.CONCLUSION:The Aldob is required for the growth,glucose homeostasis and fructose tolerance in mice.

关 键 词：醛缩酶B 基因敲除 生长发育 果糖耐受 血糖稳态 

分 类 号：Q591.4[生物学—生物化学] R363.2[医药卫生—病理学]