Obstetrics and Gynecology Department, Beijing University First Hospital, China.
J Ethnopharmacol. 2012 Aug 1;142(3):769-75. doi: 10.1016/j.jep.2012.05.059. Epub 2012 Jun 7.
Cimicifuga racemosa (L.) Nutt. (CR), known as black cohosh, has been used in Europe as a medicinal plant for more than a century and its roots have been widely used for the treatment of menopausal symptoms. Remifemin, the main ingredient in liquid or tablet medications prepared from isopropyl alcohol extracts of black cohosh rhizome, has also been evaluated in clinical studies.
To observe changes in the expression of the c-Fos protein in the hypothalamic nuclei of four groups of rats-sham-operated group (SHAM), ovariectomized (OVX) group, ovariectomized group treated with estrogen(OVX+E), and ovariectomized group treated with the isopropanol extract of Cimicifuga racemosa (OVX+ICR)-and to investigate the mechanisms of black cohosh and estrogen that take place in the hypothalamic nuclei of ovariectomized rats.
Fifty rats were assigned to each of the four groups and placed in incubators at 4 °C, 10 °C, 25 °C, 33 °C, or 38 °C for 2 h. They were then anesthetized, and their brains were removed after heart perfusion. c-Fos expression in the hypothalamic nuclei was evaluated using immunohistochemical methods.
In the median preoptic nucleus (MnPO), ventromedial preoptic nucleus (VMPO), and suprachiasmatic nucleus (SCh) of the SHAM group, in the anterior hypothalamic area (AH) and supraoptic nucleus (SO) of all four groups, and in the paraventricular nucleus (PVN) of the SHAM, OVX and OVX+E groups, the c-Fos-positive cell densities all changed in a similar manner: the cell density decreased when the temperature was less than 25 °C and the density increased when the temperature was greater than 25 °C, demonstrating a V-type curve. The c-Fos density was lowest at 25°C. The other nuclei demonstrated irregular changes. The positive cell densities in the MnPO, AH, and PVN of the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX group at all temperatures, except 25 °C. Positive cell densities in the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX groups in the MPA at 25 °C, in the VMPO at 4 °C, 33 °C, and 38 °C, in the SO at 4 °C, 10 °C, and 38 °C, and in the SCh at 33 °C.
Regardless of the temperature, positive cell densities were lower in the MnPO, MPA, VMPO, AH, SCh, SO, and PVN of the OVX groups in comparison with the densities measured in the same sites in the SHAM group. Following the administration of black cohosh and estrogen, the positive cell densities in the OVX groups increased and became closer to, or exceeded, those measured in the SHAM group, suggesting that both drugs may act on the hypothalamic nuclei and have therapeutic effects on menopausal symptoms.
ETHNOPHARMACOLOGICAL 相关性：升麻（升麻属）（L.）Nutt.（CR），俗称黑升麻，在欧洲已被用作药用植物一个多世纪，其根已被广泛用于治疗更年期症状。Remifemin，从黑升麻根茎的异丙醇提取物中制备的液体或片剂药物的主要成分，也已在临床研究中进行了评估。
观察四组大鼠下丘脑核中 c-Fos 蛋白表达的变化 - 假手术组（SHAM），卵巢切除（OVX）组，卵巢切除并用雌激素治疗组（OVX+E）和卵巢切除并用黑升麻异丙醇提取物治疗组（OVX+ICR）-并探讨黑升麻和雌激素在卵巢切除大鼠下丘脑核中发生的机制。
将 50 只大鼠分别分配到四组中的每组，并在 4°C、10°C、25°C、33°C 或 38°C 的孵育箱中放置 2 小时。然后对它们进行麻醉，并在心脏灌注后取出大脑。使用免疫组织化学方法评估下丘脑核中 c-Fos 的表达。
在假手术组的中视前核（MnPO）、视前腹内侧核（VMPO）和视交叉上核（SCh）、所有四组的下丘脑前区（AH）和视上核（SO）以及室旁核（PVN）中，SHAM、OVX 和 OVX+E 组的 c-Fos 阳性细胞密度均以相似的方式变化：当温度低于 25°C 时，细胞密度降低，当温度高于 25°C 时，细胞密度增加，呈 V 型曲线。25°C 时细胞密度最低。其他核显示不规则变化。SHAM、OVX+E 和 OVX+ICR 组的 MnPO、AH 和 PVN 中的阳性细胞密度在所有温度下均高于 OVX 组，除 25°C 外。SHAM、OVX+E 和 OVX+ICR 组在 25°C 时的 MPA、4°C、33°C 和 38°C 时的 VMPO、4°C、10°C 和 38°C 时的 SO 以及 33°C 时的 SCh 的阳性细胞密度均高于 OVX 组。
无论温度如何，OVX 组的 MnPO、MPA、VMPO、AH、SCh、SO 和 PVN 中的阳性细胞密度均低于 SHAM 组中相同部位测量的密度。给予黑升麻和雌激素后，OVX 组的阳性细胞密度增加，接近或超过 SHAM 组的测量值，表明这两种药物可能作用于下丘脑核，对更年期症状具有治疗作用。
