双侧卵巢切除术和他莫昔芬给药诱发的潮热模型大鼠证候评价  

Evaluation of hot-flash model rats induced by bilateral oophorectomy and tamoxifen administration

作　　者：谢海纳 潘志强[1] 曹琳娜 XIE Haina;PAN Zhiqiang;CAO Linna(School of Traditional Chinese Medical,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中医学院,上海201203

出　　处：《中国实验动物学报》2023年第12期1545-1554,共10页Acta Laboratorium Animalis Scientia Sinica

基　　金：上海市科委项目(19140905000);Funded by Shanghai Science and Technology Commission Project(19140905000)。

摘　　要：目的探索用于妇女潮热现象研究的证候动物模型。方法24只雌性SD大鼠随机分为假手术组、双侧卵巢切除组和他莫昔芬组,每组8只,分别采用双侧卵巢切除术和灌胃10 mg/(kg·d)他莫昔芬模拟两种潮热动物模型。在造模第14和28天,检测大鼠旷场活动、肛温、体表红外热像图等表征信息。第29天处死大鼠,取子宫称重并制作病理切片;ELISA检测血液雌二醇与儿茶酚胺类物质含量;RT-qPCR检测肾上腺性激素合成酶(Star、Cyp11a1、Cyp17a1、Cyp19a1、Por、Hsd3b2、Hsd17b1)基因表达,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,双侧卵巢切除组大鼠体重增长显著(P<0.01),而他莫昔芬组大鼠体重增长缓慢。双侧卵巢切除组大鼠体表最高温度在第28天显著下降(P<0.01),类似于阳虚表现,而其腹部最高温度与最低温度之差在第14天显著升高(P<0.05)、背部最高温度与最低温度之差在第28天显著升高(P<0.01),类似于内热表象,且大鼠旷场活动度下降(P<0.01),类似于精气不足表现;他莫昔芬组大鼠给药14 d其体表最高温度显著下降(P<0.01),但大鼠旷场活动度上升(P<0.01)。两种造模方式均导致大鼠子宫指数呈明显下降(P<0.01)。与假手术组相比,双侧卵巢切除组和他莫昔芬组E2均显著下降(P<0.01),NE、Epi均呈降低趋势(P<0.05),双侧卵巢切除组β-EP也明显下降(P<0.05);与假手术组相比,双侧卵巢切除大鼠肾上腺Cyp11a1基因表达显著上升(P<0.05),而Cyp17a1与Hsd17b1基因表达显著下降(P<0.05);他莫昔芬组Star与Por基因表达显著上升(P<0.01),而Cyp17a1基因表达量明显下降(P<0.01);双侧卵巢切除组Pnmt基因表达显著下调(P<0.01)。结论双侧卵巢切除SD大鼠可以用于围绝经期潮热的研究,其证候特征类似于中医的肾阳不足兼阴虚内热。Objective To explore the animal model of syndrome used in the study of hot flash phenomenon in women.Methods Twenty-four female SD rats were divided randomly into three groups:Con group,Ovx group,and tamoxifen group(n=8 rats per group).Hot flashes were induced by bilateral oophorectomy and intragastric tamoxifen 10 mg/(kg·d),respectively.Open-field activity,anal temperature,and body surface infrared thermograms were detected on model days 14 and 28.The rats were then killed on day 29 and their uteruses were removed,weighed,and sectioned.Blood estradiol and catecholamine levels were determined by enzyme-linked immunosorbent assay.Gene expression levels of adrenal sex hormone synthetases(Star,Cyp11a1,Cyp17a1,Cyp19a1,Por,Hsd3b2,Hsd17b1)and catecholamine synthetases(Th,Ddc,Dbh,Pnmt)in the adrenal medulla were detected by reverse transcription-polymerase chain reaction.Results Rat body weight was significantly higher in the Ovx group compared with Con group(P<0.01),while body weight increased slowly in the tamoxifen group.The maximum body surface temperature was significantly decreased on day 28 in the Ovx group(P<0.01),the difference between the maximum and minimum abdominal temperatures was significantly increased on day 14(P<0.05),the difference between the maximum and minimum temperatures on the back was significantly increased on day 28(P<0.01),and the open-field activity was decreased(P<0.01).Compared with the sham operation group,the maximum body surface temperature in the tamoxifen group was significantly decreased(P<0.01)but the open-field activity was increased(P<0.01).The uterine index was significantly decreased in both models(P<0.01).Estradiol levels were significantly decreased(P<0.01)and NE and epinephrine were also significantly decreased in the Ovx group compared with Con group(P<0.05),andβ-EP was also significantly decreased in Ovx group(P<0.05).Adrenal Cyp11a1 gene expression was significantly increased(P<0.05)while Cyp17a1 and Hsd17b1 gene expression levels were significantly decreased(P<0.05)in

关 键 词：潮热 双侧卵巢切除 他莫昔芬 动物模型 

分 类 号：Q95-33[生物学—动物学]