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
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上海中医药大学

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Syndrome evaluation of hot flash model rats induced by bilateral oophorectomy and tamoxifen administration
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Shanghai University of Traditional Chinese Medicine

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    摘要:

    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三组,每组8只,分别采用双侧卵巢切除术和灌胃10 mg/kg/d他莫昔芬复制两种潮热动物模型。在造模第14天和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检测血液雌二醇与肾上腺素含量;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:与假手术组比较,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),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),且大鼠旷场活动度下降(P<0.01);他莫昔芬组大鼠给药14天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均呈明显下降(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);与假手术组比较,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与阴虚内热。

    Abstract:

    【Abstract】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 randomly divided into three groups: sham operation group, bilateral oophorectomy group and tamoxifen group, with 8 rats in each group. Two kinds of hot flash animal models were induced by bilateral oophorectomy and tamoxifen intragastory at 10 mg/kg/d, respectively. On the 14th and 28th days of modeling, the open field activity, anal temperature and body surface infrared thermogram of rats were detected. On the 29th day, the rats were killed, and the uterus was weighed and pathological sections were made. Blood estradiol and epinephrine were determined by ELISA. The gene expressions of adrenal sex hormone synthetase (Star, Cyp11a1, Cyp17a1, Cyp19a1, Por, Hsd3b2, Hsd17b1) and catecholamine substance synthetase (Th, Ddc, Dbh, Pnmt) in adrenal medulla were detected by RT-qPCR. Results Compared with sham operation group, the body weight of rats in bilateral ovariectomy group increased significantly (P < 0.01), while the body weight of tamoxifen group increased slowly. In the bilateral ovariectomies group, the maximum body surface temperature was significantly decreased on day 28 (P < 0.01), the difference between the maximum temperature and the minimum temperature in the abdomen was significantly increased on day 14 (P < 0.05), the difference between the maximum temperature and the minimum temperature in the back was significantly increased on day 28 (P < 0.01), and the open field activity of the rats was decreased (P < 0.01). The maximum body surface temperature of the tamoxifen group was significantly decreased (P < 0.01), but the open field activity of the rats was increased (P < 0.01). The uterine index of rats decreased significantly in both models (P < 0.01). Compared with sham operation group, E2 in bilateral oophorectomy group and tamoxifen group was significantly decreased (P < 0.01), NE and Epi were significantly decreased (P < 0.05), β-EP in bilateral oophorectomy group was also significantly decreased (P < 0.05). Compared with sham operation group, the adrenal Cyp11a1 gene expression in bilateral ovariectomized rats was significantly increased (P < 0.05), while the Cyp17a1 and Hsd17b1 gene expressions were significantly decreased (P < 0.05). The gene expressions of Star and Por in tamoxifen group were significantly increased (P < 0.01), while the gene expression of Cyp17a1 was significantly decreased (P < 0.01). Pnmt gene expression was significantly down-regulated in bilateral oophorectomy group (P < 0.01). conclusion Bilateral ovariectomized rats can be used for the study of perimenopausal hot flashes, whose syndromes are similar to those of kidney Yang deficiency and Yin deficiency in traditional Chinese medicine.

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  • 收稿日期:2023-06-16
  • 最后修改日期:2023-11-15
  • 录用日期:2023-11-15
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