高尿酸血症对雌性大鼠生殖功能的影响及其机制  

Influence of hyperuricemia on the reproductive function of female rats and its mechanism

作　　者：龚雪琳 邹通 宋淼 刘呈杨 张清[1] 孙钰 邢士超[1,2] GONG Xuelin;ZOU Tong;SONG Miao;LIU Chengyang;ZHANG Qing;SUN Yu;XING Shichao(Department of Pathogenic Microbiology,School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院病原生物学系,山东青岛266071 [2]青岛大学附属青岛妇女儿童医院

出　　处：《精准医学杂志》2024年第3期213-217,共5页Journal of Precision Medicine

基　　金：国家自然科学基金资助项目(81671625);教育部产学合作协同育人项目(220605402021719);山东省自然科学基金(ZR2023MH304);山东省医药卫生科技发展计划项目(20-2222010801);北京大学人民医院研究与发展基金(RDGS2022-14);青岛市医药卫生科研指导项目(2022WJZD136)。

摘　　要：目的探讨高尿酸血症(HUA)对雌性大鼠生殖功能的影响及其机制。方法雌性Wistar大鼠18只,随机分为3组,每组各6只。高尿酸组(HUA组)和高尿酸恢复组(HR组)大鼠每天灌胃50 mg/kg尿酸及腹腔注射250 mg/kg氧嗪酸钾,至第9周时,HR组大鼠改用等体积生理盐水进行灌胃和腹腔注射,HUA组不变,再继续处理7周;对照组(N组)大鼠给予相同体积的生理盐水灌胃及腹腔注射,持续16周。第16周时,测量三组大鼠体质量和子宫、卵巢质量,并计算子宫、卵巢系数;苏木精-伊红染色法观察3组大鼠子宫、卵巢组织的病理变化;酶联免疫吸附试验法检测3组大鼠血清中促性腺激素释放激素(GnRH)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)含量;使用阴道脱落细胞涂片法观察3组大鼠动情周期;采用比色法检测3组大鼠子宫组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)水平;采用免疫荧光法检测3组大鼠子宫组织中肿瘤坏死因子α(TNF-α)的荧光强度。结果与N组大鼠相比,HUA组大鼠子宫系数降低、卵泡数量减少、子宫内膜厚度变薄,动情间期缩短,血清FSH水平增加,子宫组织中SOD、GSH水平降低,而MDA含量增加(F=7.80~111.40,t=3.95~12.37,P<0.05),子宫组织中TNF-α荧光强度增高;与HUA组大鼠相比,HR组卵泡数量显著增多、子宫内膜显著变厚,血清中FSH水平增高,子宫组织中SOD、GSH水平显著增高,而MDA水平显著降低(t=3.40~11.56,P<0.05),子宫组织中TNF-α荧光强度降低。结论HUA可致雌性大鼠生殖功能下降,其可能机制与大鼠血清尿酸水平升高,致性激素分泌紊乱、机体氧化应激水平增高,进而诱导炎症反应发生有关。Objective To investigate the influence of hyperuricemia(HUA)on the reproductive function of female rats and its mechanism.Methods A total of 18 female Wistar rats were randomly divided into HUA group,HUA recovery group(HR group),and control group(N group),with 6 rats in each group.The rats in the HUA group and the HR group were given intragastric administration of 50 mg/kg uric acid and intraperitoneal injection of 250 mg/kg oteracil potassium every day,and since week 9,the rats in the HR group were given an equal volume of normal saline by gavage and intraperitoneal injection,while the treatment remained unchanged for those in the HUA group,for another 7 weeks;the rats in the N group were given an equal vo-lume of normal saline by gavage and intraperitoneal injection for 16 weeks.At week 16,body weight,uterine mass,and ovarian mass were measured for all three groups,and uterine and ovarian coefficients were calculated;hematoxylin-eosin staining was used to observe the pathological changes of the uterus and ovarian tissue;enzyme-linked immunosorbent assay was used to measure the serum levels of gonadotropin-releasing hormone(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2);the vaginal exfoliation cell smear method was used to observe the estrous cycle of rats;colorimetry was used to measure the levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)in uterine tissue of the three groups;immunofluorescence assay was used to measure the fluorescence intensity of tumor necrosis factor-α(TNF-α)in uterine tissue of the three groups.Results Compared with the N group,the HUA group had significant reductions in uterine coefficient,number of follicles,endometrial thickness,and estrous interval,a significant increase in the serum level of FSH,significant reductions in the levels of SOD and GSH in uterine tissue,and a significant increase in the content of MDA(F=7.80-111.40,t=3.95-12.37,P<0.05),as well as an increase in the fluorescence intensity of TNF-αin uterine ti

关 键 词：高尿酸血症 动情期 性腺甾类激素 细胞因子类 炎症 氧化性应激 女(雌)性 大鼠 Wistar 

分 类 号：R589.7[医药卫生—内分泌] R711.5[医药卫生—内科学]