补锌对PKA/CREB信号通路及边缘锌缺乏小鼠生精功能的影响  

Effects of zinc supplementation on PKA/CREB signaling pathway and spermatogenic function in marginal zinc deficiency mice

作　　者：王子琼 王蕾 于露 彭程 马海涛 叶静萍[2] 汪春红[1] WANG Zi-qiong;WANG Lei;YU Lu;PENG Cheng;MA Hai-tao;YE Jing-ping;WANG Chun-hong(School of Public Health,Wuhan University,Wuhan Hubei 430071,China;Department of Pediatrics,Renmin Hospital of Wuhan University,Wuhan Hubei 430071,China)

机构地区：[1]武汉大学公共卫生学院,湖北武汉430071 [2]武汉大学人民医院儿科,湖北武汉430071

出　　处：《毒理学杂志》2022年第6期496-501,共6页Journal of Toxicology

基　　金：安琪纽特营养基金项目(AF2019004)。

摘　　要：目的探讨补锌对蛋白激酶A(protein kinase A,PKA)/环磷酸腺苷反应元件结合蛋白(cAMP-response element binding protein,CREB)(PKA/CREB)通路及边缘锌缺乏(marginal zinc dificiency,MZD)雄性小鼠生精功能的影响。方法75只4周龄SPF级ICR雄性小鼠随机分为对照组(饲料锌含量为30 mg/kg)、MZD组(饲料锌含量为10 mg/kg)和低(MZD+ZnY2,饲料锌10 mg/kg+补锌2 mg/kg·bw)、中(MZD+ZnY4,饲料锌10 mg/kg+补锌4 mg/kg·bw)、高(MZD+ZnY8,饲料锌10 mg/kg+补锌8 mg/kg·bw)剂量组,每天1次灌胃补锌。35 d后,检测精子质量、锌含量、血清性激素水平、以及CREB、PKA和激素合成相关基因StAR、3β-HSD、P450scc和CYP17A1 mRNA相对表达水平。结果各实验组小鼠间体重和饮水、摄食量差异无统计学意义。与对照组比较,MZD组精子存活率、低渗肿胀率、血清锌和T含量均降低,精子畸形率升高;CREB、PKA以及StAR、3β-HSD、P450scc mRNA相对表达量降低(P<0.05)。与MZD组比较,MZD+ZnY 4和MZD+ZnY 8组精子存活率,低渗肿胀率均明显回升,精子畸形率降低(P<0.05);MZD+ZnY8组血清锌水平明显回升(P<0.05);MZD+ZnY2组3β-HSD、CREB mRNA以及MZD+ZnY4组3β-HSD、P450scc mRNA相对表达量均明显回升(P<0.05)。结论锌可通过PKA/CREB信号通路调控性激素水平影响雄性小鼠生精功能;适量补锌能综合改善MZD小鼠精子质量。Objective To investigate the effects of zinc supplementation on the protein kinase A/cAMP-response element binding protein(PKA/CREB)pathway and spermatogenic function in marginal zinc deficiency mice.Methods Seventy-five male four week-old SPF-grade ICR mice were randomly divided into control group(Zinc content of the feed was 30 mg/kg),marginal zinc deficiency group(MZD,Zinc content of the feed was 10 mg/kg),low(MZD+ZnY2,Zinc content of the feed was 10 mg/kg+zinc supplement in 2 mg/kg·bw),medium(MZD+ZnY4,Zinc content of the feed was 10 mg/kg+zinc supplement in 4 mg/kg·bw)and high(MZD+ZnY8,Zinc content of the feed was 10 mg/kg+zinc supplement in 8 mg/kg·bw),zinc was supplemented by gavage once a day.After 35 days,sperm quality,zinc,sexual hormone in serum,and the relative expression levels of CREB,PKA,StAR,3β-HSD,P450scc and CYP17A1 mRNA were measured.Results There were no significant differences in body weight,water intake and feeding intake among the experimental groups.Compared with the control group,sperm viability and hypoosmotic swelling rate were decreased,sperm malformation rate was increased,the levels of serum zinc and T,and the expressions of CREB,PKA,StAR,3β-HSD,P450scc mRNA were all decreased in the MZD group,the difference was statistically significant(P<0.05).Compared with the MZD group,sperm viability and hypoosmotic swelling rate were increased,and the sperm malformation rate reduced in MZD+ZnY4 and 8 groups(P<0.05);the serum zinc level significantly was increased in the MZD+ZnY8 group(P<0.05);the expressions of 3β-HSD and P450scc mRNA in the MZD+ZnY2 group and 3β-HSD and P450scc mRNA in the MZD+ZnY4 group were increased significantly(P<0.05).Conclusion Zinc may affect the spermatogenic function of male mice through the PKA/CREB signaling pathway.Zinc supplementation at appropriate dose can improve sperm quality in MZD mice.

关 键 词：锌 睾丸 蛋白激酶A/环磷酸腺苷反应元件结合蛋白 睾酮 生精 

分 类 号：R15[医药卫生—营养与食品卫生学] R114[医药卫生—公共卫生与预防医学] R99