DHEA诱导的PCOS大鼠中高雄激素对肝细胞凋亡影响的初步探索  

Study on effects of hyperandrogenism on hepatocyte apoptosis in DHEA induced PCOS rats

作　　者：张婷婷 高慧民 谷牧青[1] 刘瑞霞 李天鹤 阴赪宏[1] ZHANG Ting-ting;GAO Hui-min;GU Mu-qing;LIU Rui-xia;LI Tian-he;YIN Cheng-hong(Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing 100026)

机构地区：[1]首都医科大学附属北京妇产医院北京妇幼保健院,北京100026

出　　处：《生殖医学杂志》2021年第11期1478-1485,共8页Journal of Reproductive Medicine

基　　金：国家自然科学基金青年项目(81801407)。

摘　　要：目的探讨多囊卵巢综合征(PCOS)大鼠内分泌代谢水平、肝脏组织结构及功能变化的特点。方法将20只3周龄SD大鼠随机分为正常对照组和脱氢表雄酮(DHEA)组,每组10只,分别皮下注射油剂、6 mg/100 g DHEA,每日1次,连续注射21 d。两组大鼠每周称重1次,造模21 d后,麻醉处死并收集大鼠血清、卵巢组织及肝脏组织。利用ELISA试剂盒及谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(ALP)试剂盒检测两组大鼠血清中生殖激素和肝生化指标水平;苏木精-伊红(HE)染色及Masson染色观察大鼠肝脏组织结构及纤维化改变;蛋白质印迹法(WB)检测大鼠肝脏组织中凋亡相关蛋白Beclin-1和Lamin B1的表达量。结果与对照组比较,DHEA组大鼠动情周期失调、卵巢组织发生囊样改变且效果显著。DHEA组大鼠血清中睾酮水平显著高于对照组大鼠(P=0.001),其胰岛素耐量试验(ITT)的曲线下面积(AUC)、肝脏重量、肝脏/体重比均较对照组显著增加(P<0.05)。HE染色显示DHEA组大鼠肝细胞间结构疏松,染色变浅可见少量脂滴形成,中央静脉周围有少量炎细胞浸润;Masson染色显示DHEA组大鼠中央静脉周围出现少量蓝色胶原纤维。DHEA组大鼠血清ALT水平较对照组显著升高(P=0.042),且与睾酮水平具有显著相关性(r=0.606,P=0.048)。WB检测显示,DHEA组Beclin-1和Lamin B1蛋白的相对表达量显著高于对照组(P<0.01)。结论肝细胞凋亡参与了PCOS大鼠肝组织损伤过程,其机制可能与机体内高雄激素血症相关。Objective:To investigate the changes of endocrine metabolism,liver tissue structure and function in rats with polycystic ovary syndrome(PCOS).Methods:Twenty 3-week-old SD rats were randomly divided into normal control group and DHEA group,10 rats for each group.Rats in the control group were subcutaneously injected with sesame oil,and rats in the DHEA group were subcutaneously injected with 6 mg/100 g DHEA,once daily for 21 days.The rats of two groups were weighed once a week.After treatment for 21 days,the rats were sacrificed under anesthesia,and the serum samples,ovarian tissue and liver tissue were collected.ELISA kits were used to detect serum sexual hormone levels and liver biochemical ALT,AST,ALP levels of the rats in two groups.HE staining and Masson staining were used to observe the changes in rat liver tissue structure and morphology.Western blot was used to detect the expression of Beclin-1 and Lamin B1 in rat liver tissue.Results:Compared with the control group,estrous cycle disorder and cyst-like changes occurred in the ovarian tissue of the DHEA group and the effect was significant.The levels of serum testosterone in DHEA group were significantly higher than that in control group(P=0.001).The area under the curve(AUC)of insulin tolerance test(ITT),liver weight and liver/body weight ratio in DHEA group were significantly higher than those in the control group(P<0.05).HE staining showed that the structure between hepatocytes in the DHEA group was loose,the staining became lighter and a small amount of lipid droplets were formed,and a small number of inflammatory cells infiltrated around the central vein.Masson staining showed a small amount of blue collagen fibers around the central vein of the rats in the DHEA group.The serum ALT level in DHEA group was significantly higher than that in the control group(P=0.042),and ALT level was significantly correlated with testosterone(r=0.606,P=0.048).Furthermore,Western blot analysis showed that the relative expression of Beclin-1 and Lamin B1 protein in DHEA g

关 键 词：多囊卵巢综合征 雄激素 肝脏 凋亡 

分 类 号：R711.75[医药卫生—妇产科学] R-332[医药卫生—临床医学]