尿酸对果蝇幼虫生长发育的影响及机制分析  

Effect and Mechanism of Uric Acid in Regulating Larval Growth and Development of Drosophila Melanogaster

作　　者：张睿迪 邱洪斌[1,2] 王景涛[3] 关宝生[1,2] 白雪[4] 尹相林[1,2] ZHANG Ruidi;QIU Hongbin;WANG Jingtao;GUAN Baosheng;BAI Xue;YIN Xianglin(School of Public Health,School of Basic Medicine Sciences,Jiamusi University,Jiamusi,Heilongjiang 154007,China;Heilongjiang Province Key Laboratory of Gout Research,School of Basic Medicine Sciences,Jiamusi University,Jiamusi,Heilongjiang 154007,China;Department of Anatomy and Histoembryology,School of Basic Medicine Sciences,Jiamusi University,Jiamusi,Heilongjiang 154007,China;Department of Pharmacy,The Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China)

机构地区：[1]佳木斯大学公共卫生学院,黑龙江佳木斯154007 [2]佳木斯大学黑龙江省痛风研究重点实验室,黑龙江佳木斯154007 [3]佳木斯大学基础医学院人体解剖与组织胚胎学教研室,黑龙江佳木斯154007 [4]哈尔滨医科大学附属第二医院药学部,哈尔滨150086

出　　处：《中国医学科学院学报》2024年第5期653-658,共6页Acta Academiae Medicinae Sinicae

基　　金：黑龙江省自然科学基金(H201374);黑龙江省痛风研究重点实验室开放课题(TFYJ202201);黑龙江省省属本科高校优秀青年教师基础研究支持计划(YQJH2023228)。

摘　　要：目的探讨尿酸(UA)对果蝇幼虫生长发育的影响及其机制。方法收集刚孵化的野生型黑腹果蝇(W1118)1龄幼虫1350只,采用高嘌呤饮食构建高尿酸血症果蝇模型,分为对照组(标准玉米粉培养基)、低浓度干预组(含0.05%腺嘌呤的玉米粉培养基)和高浓度干预组(含0.10%腺嘌呤的玉米粉培养基),每组150只,另设2个平行实验组,观察各组幼虫的生长发育情况,测定果蝇体内UA和激素水平,以及生长发育相关基因的表达情况。结果与对照组比较,低浓度干预组和高浓度干预组果蝇体内UA水平均显著增高(P均<0.001)、果蝇幼虫发育时间显著延长(P=0.024,P<0.001),高浓度干预组果蝇幼虫的生存率、蛹化率、羽化率均显著降低(P均<0.001),而果蝇幼虫体内保幼激素(JH)、20-羟基蜕皮甾酮(20E)水平均显著升高(P均<0.001)。PCR结果显示,与对照组比较,高浓度干预组果蝇幼虫体内活性氧(ROS)、叉头框O亚型(FOXO)、哺乳动物雷帕霉素靶蛋白(mTOR)mRNA的表达水平显著增高,应激诱导蛋白Sestrin、mTOR复合物1(mTORC1)、AMP活化的蛋白激酶mRNA的表达水平显著降低(P均<0.001)。结论高浓度UA可能通过调节果蝇体内JH、20E的表达,促进ROS/FOXO/mTORC1/mTOR信号通路的表达水平,从而抑制果蝇幼虫的生长发育。Objective To explore the effect and mechanism of uric acid(UA)in regulating the larval growth and development of Drosophila melanogaster.Methods A total of 1350 newly hatched first-instar larvae of wild-type Drosophila melanogaster(W1118)were collected,and the Drosophila melanogaster model of hyperuricemia was constructed with a high purine diet.The larvae were assigned into three groups(n=150):control(standard corn meal medium),low-dose adenine(corn meal medium containing 0.05% adenine),and high-dose adenine(corn meal medium containing 0.10% adenine),and two parallel groups were set up.The growth and development of larvae in each group was observed,and the UA and hormone levels were measured.In addition,the expression levels of genes involved in growth and development were determined.Results Compared with the control group,the low-and high-dose adenine groups showed elevated UA levels(both P<0.001)and prolonged developmental period(P=0.024,P<0.001).The high-dose adenine group showed decreased survival rate,pupation rate,and eclosion rate and elevated levels of juvenile hormone(JH)and 20-hydroxyecdysone(20E)(all P<0.001).The PCR results showed that compared with the control group,high-dose adenine upregulated the mRNA levels of reactive oxygen species(ROS),forkhead box O(FOXO),and mammalian target of rapamycin(mTOR)while downregulating the mRNA levels of Sestrin,mTOR complex 1(mTORC1),and AMP-activated protein kinase(all P<0.001).Conclusion High concentrations of UA may promote the expression of ROS/FOXO/mTORC1/mTOR signaling pathway by regulating the levels of JH and 20E,thereby inhibiting the larval growth and development of Drosophila melanogaster.

关 键 词：尿酸 果蝇 活性氧 叉头框转录因子 哺乳动物雷帕霉素靶蛋白复合物1 

分 类 号：R589.7[医药卫生—内分泌]