卵巢功能丧失大鼠肾上腺皮质-髓质功能的动态变化OA
Dynamic changes in adrenal cortex-medulla function in rats with ovarian function loss
目的 探讨卵巢功能丧失对大鼠肾上腺皮质与髓质功能的影响.方法 将36只雌性SD大鼠随机分为假手术组和卵巢切除术组,每组18只.于术后第14、28、42天分三批处死,检测指标包括:(1)肾上腺皮质与髓质组织学(苏木素-伊红(HE)染色)与超微结构(透射电镜);(2)ELISA检测血清雌二醇(E2)、硫酸脱氢表雄酮(DHEAS)、促性腺激素释放激素(GnRH)、促卵泡素(FSH)、促黄体激素(LH)、多巴胺(DA)、去甲肾上腺素(NE)、肾上腺素(EPI)水平;(3)RT-qPCR检测肾上腺皮质雌激素生成相关酶(Cyp17a1、Cyp19a1、Cyb5a、Hsd17 b1、Hsd17b3、Hsd3b2、Akr1c3、Por)及肾上腺髓质儿茶酚胺物质合成酶(Th、Ddc、Dbh、Pnmt)基因表达.结果 与假手术组相比,卵巢切除组大鼠:(1)体质量增长明显;(2)血清E2、DHEAS、GnRH浓度呈下降趋势,术后第28、42天GnRH水平显著下降(P<0.01),血清LH水平则在术后第42天出现了极为显著的上升(P<0.001),同期EPI水平也显著升高(P<0.05);(3)肾上腺皮质网状带及髓质的组织学与超微结构呈现随时间推移的动态改变.皮质网状带表现为细胞索直径增大、细胞密度增高及胞质嗜酸性显著增强;超微结构方面,术后14 d可见局部胞浆溶解和线粒体嵴缩窄,至28 d时出现溶酶体增多、线粒体结构模糊及脂滴增加,42 d时进一步表现为线粒体与脂滴丰富、内质网扩张,与之相比,髓质组织学结构及细胞内颗粒分布未见显著变化,但其超微结构亦有时序性改变:术后14 d NE分泌颗粒增多伴轻度线粒体肿胀,28 d时线粒体肿胀持续存在,至42 d则见线粒体肿胀稍减轻,而NE分泌颗粒数量减少;(4)肾上腺皮质雌激素生成相关酶基因表达改变:术后第14天Cyp19a1表达上调(P<0.05),术后第42天Cyp17a1、Cyb5a、Hsd17b1表达显著上调(P<0.01);(5)肾上腺髓质儿茶酚胺物质合成酶基因表达变化:术后第42天,肾上腺Th(P<0.001)、Ddc(P<0.01)、Dbh(P<0.05)、Pnmt(P<0.001)基因表达均显著上调.结论 卵巢功能丧失与大鼠肾上腺皮质及髓质的改变相关,表现为组织形态学、超微结构及雌激素生成相关基因表达的适应性调整.
Objective To investigate the effects of ovarian function loss on adrenal cortex and medulla function in rats.Methods Thirty-six female SD rats were divided randomly into sham operation and ovariectomy groups(n=18).The rats were sacrificed in three batches at 14,28,and 42 d after surgery.The following parameters were measured:(1)Histology(hematoxylin/eosin staining)and ultrastructure(transmission electron microscopy)of adrenal cortex and medulla.(2)Serum levels of estradiol(E2),dehydroepiandrosterone sulfate(DHEAS),gonadotropin-releasing hormone(GnRH),follicle-stimulating hormone,luteinizing hormone(LH),dopamine,norepinephrine,and epinephrine(EPI)(enzyme-linked immunosorbent assay).(3)Gene expression of enzymes related to estrogen production in the adrenal cortex(Cyp17a1,Hsd3b2,Hsd17b1,Hsd17b3,Akr1c3,Cyp19a1,Por,Cyb5a)and catecholamine substance synthetases(Th,Ddc,Dbh,Pnmt)in the adrenal medulla(reverse transcription-quantitative polymerase chain reaction).Results Compared with the sham operation group,rat in the ovariectomy group:(1)Rats in the ovariectomy group showed significant body mass gain.(2)Downward trends in serum concentrations of E2,DHEAS,and GnRH,with a significant decrease in GnRH levels on days 28 and 42 after surgery(P<0.01),significant increases in serum LH(P<0.001)and EPI levels(P<0.05)on day 42 after surgery.(3)Time-dependent dynamic changes in the histology and ultrastructure of the adrenal cortical zona reticularis and medulla.The zona reticularis exhibited increased cord diameter,higher cell density,and significantly enhanced cytoplasmic eosinophilia.Ultrastructurally,localized cytoplasmic dissolution and mitochondrial cristae narrowing were observed on day 14,increased lysosomes,blurred mitochondrial structures,and lipid droplet accumulation on day 28,and further mitochondrial and lipid droplet enrichment with dilated endoplasmic reticulum on day 42.In contrast,the medulla showed no significant histological changes or granular distribution,but ultrastructural alterations were time-dependent:increased norepinephrine secretory granules with mild mitochondrial swelling on day 14,persistent mitochondrial swelling on day 28,and reduced mitochondrial swelling with decreased norepinephrine granules on day 42.(4)The ovariectomy group also showed changes in gene expression of enzymes related to estrogen production in the adrenal cortex:Cyp19a1 expression was upregulated on day 14(P<0.05)and Cyp17a1,Cyb5a,and Hsd17b1 were significantly upregulated on day 42 after surgery(P<0.01).(5)Regarding catecholamine substance synthetases in the adrenal medulla,gene expression levels of Th(P<0.001),Ddc(P<0.01),Dbh(P<0.05)and Pnmt(P<0.001)in the adrenal gland were all significantly upregulated on day 42 after surgery in the ovariectomy group compared with the sham operation group.Conclusions Ovarian dysfunction is associated with alterations in the adrenal cortex and medulla in rats,manifested as adaptive adjustments in tissue morphology,ultrastructure and the expression of estrogen-related genes.
白雅兆;潘志强;曹琳娜;彭佩克
上海中医药大学中医学院,上海 201203上海中医药大学中医学院,上海 201203上海中医药大学中医学院,上海 201203上海中医药大学中医学院,上海 201203
生物科学
肾上腺皮质网状带肾上腺髓质卵巢切除雌激素大鼠
adrenal cortex zona reticularisadrenal medullaoophorectomyestrogenrat
《中国实验动物学报》 2026 (8)
1135-1145,11
国家自然科学基金面上项目(82374307).Funded by National Natural Science Foundation of China General Program(82374307).
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