组蛋白去乙酰化酶在卵巢切除小鼠骨髓间充质干细胞中的表达

背景：骨髓间充质干细胞的多向分化能力在骨代谢疾病中发挥重要作用,受激素、细胞因子等多种因素调节。目前骨髓间充质干细胞骨向分化的表观遗传学调控机制尚不明确,组蛋白去乙酰化酶与骨质疏松的关系尚需进一步探讨。 目的：建立雌激素缺乏骨质疏松小鼠的实验动物模型,检测骨髓间充质干细胞组蛋白去乙酰化酶1,3,4 mRNA表达水平,探索卵巢切除小鼠骨组织形成障碍的表观遗传学机制。 方法：昆明种小鼠30只随机等分为模型组和假手术组。小鼠适应性喂养7 d后,模型组小鼠切除双侧卵巢,造成雌激素缺乏骨质疏松实验动物模型,假手术组小鼠仅切除等量脂肪组织。 结果与结论：模型组小鼠股骨骨小梁稀疏或断裂,骨小梁宽度变窄,骨小梁间距变宽,骨小梁占视野面积降低。与假手术组相比,模型组小鼠骨髓间充质干细胞中组蛋白去乙酰化酶3 mRNA表达水平显著降低,组蛋白去乙酰化酶1,4表达水平变化差异无显著性意义。提示雌激素缺乏导致骨髓间充质干细胞去乙酰化状态改变可能是骨形成障碍的重要原因之一。     

Effect of aqueous extract of Solanum xanthocarpum Schrad. ＆ Wendl. on postmenopausal syndrome in ovariectomized rats

OBJECTIVE： Solanum xanthocarpum Schrad. ＆ Wendl. （Solanaceae） is present in many Ayurveda compound formulations including Chavanaprasha and Dasamoolarishta. The whole plant is used in conditions such as inflammation, constipation and promoting conception in females. In the present study, we carried out different tests to evaluate the effect of aqueous extract of Solanum xanthocarpum （SXE） in postmenopausal syndrome. METHODS： The study was carried out in bilaterally ovariectomized one-month-old Wistar rats （40-50 g）. Bilaterally ovariectomized （OVX） Wistar rats were divided into four groups （n=6） receiving different treatments, consisting of a vehicle （distilled water）, aqueous extract of Solanum xanthocarpum at two different doses （200 and 400 mg/kg） administered orally daily for 90 d and standard drug β estradiol at a dose of 1 mg/kg administered subcutaneously biweekly for 90 d. Estrogenic activity was assessed by vaginal cornification, sexual behavior, serum estradiol and uterine weight to body weight ratio. Antiosteoporotic activity was assessed on the basis of biomechanical and biochemical parameters followed by histopathological studies, and antidepressant activity was assessed by forced swim test. RESULTS： SXE showed presence of steroids. At the dose of 200 mg/kg, it significantly improved all the parameters of sexual behavior （P〈0.01）, caused vaginal cornification, and increased serum estradiol and uterine weight （P〈0.01）. It also significantly improved all the parameters of bone strength as well as depression （P〈0.01）. Histopathology of bones confirmed the above findings. CONCLUSION： The study indicated that SXE may provide an effective treatment in the prevention of postmenopausal symptoms.     

蛇床子总香豆素对去卵巢骨骼的影响(英文)

蛇床子总香豆素(TCFC)5g·kg~(-1)·d~(-1)ig,每周6次,持续7wk。不脱钙骨制片测量。结果:(1)去卵巢喂水模型组胫骨骨小梁明显减少(-44％),出现骨吸收大于形成的骨高转化率。(2)用TCFC治疗的去卵巢组与(1)比胫骨骨小梁的面积增加( 41％),并降低骨高转化率的指标使基本接近对照组(除类骨质外,但矿化延迟时间不变)。本文提示TCFC可能防止绝经早期由骨高转化率引起的骨丢失。     

Effects of Ovariectomy on GnRH Neuronal Morphology inRhesus Monkey (Macaca mulatta)

Gonadotropin releasing hormone (GnRH) neurons are typically simple, fusiform cells; however, over the course of prepubertal development increasing numbers take on a 'spiny' appearance. Following gonadectomy there is a decrease in the frequency of these spiny GnRH neurons. These observations which were made in the rat suggest that GnRH neurons are directly affected by the gonadal steroid milieu, though they do not themselves contain receptors for these steroidal hormones. In that there are important species differences in the hypothalamic-pituitary-gonadal axis between rats and primates, the present study was undertaken to determine whether a reduction in ovarian hormones would produce similar changes in the morphology of GnRH neurons in the monkey. A further aim was to determine whether such changes were localized to a specific brain region.     

Ovariectomy Increases in vivo Luteinizing Hormone-Releasing Hormone Release in Pubertal, but not Prepubertal, Female Rhesus Monkeys

In pubertal, but not prepubertal, monkeys ovariectomy (OVX) results in an elevation of circulating luteinizing hormone (LH) levels. To determine if the castration-induced LH increase in pubertal monkeys is due to an increase in pulsatile LH-releasing hormone (LHRH) release, effects of OVX on in vivo LHRH release in the stalk-median eminence were examined in fully conscious monkeys using a push-pull perfusion method. The average ages (± SEM) of female rhesus monkeys in each group at OVX were 14.5±0.6 months (n = 6; prepubertal), 25.0±1.3 months (n = 5; early pubertal) and 37.8 ± 2.1 months (n = 6; midpubertal). Perfusate samples from the stalk-median eminence were obtained in 10-min fractions for 6 h in the morning (0600 to 1200 h) and 6 h in the evening (1800 to 2400 h), from the same subjects before OVX, and at 29 days and approximately 100 days after OVX. LHRH levels in perfusates were measured by radioimmunoassay. LH levels throughout the experiment were monitored by periodic blood sampling. OVX resulted in a significant LH increase in early and midpubertal monkeys (P> 0.001 for both), but not in prepubertal monkeys. Similarly, OVX in early and midpubertal monkeys increased mean LHRH release when examined 29 days after surgery (P> 0.05 and P> 0.01, respectively). The OVX-induced LHRH increases in early and midpubertal monkeys remained elevated at approximately 100 days postcastration. Furthermore, it was found that effects of OVX on the increased LHRH release were primarily due to the elevation of basal release and pulse amplitude, but not pulse frequency. In contrast, OVX did not cause any significant effects on pulsatile LHRH release in prepubertal monkeys. The results indicate that an increase in LHRH release and a concomitant increase in circulating LH occurs after OVX in pubertal monkeys, but not in prepubertal monkeys. These data are consistent with the hypothesis that the low level of LH in circulation before the onset of puberty is due to a low amount of LHRH release which is independent of ovarian steroid feedback and that the maturity of the neuronal control system for the pulsatile LHRH release is responsible for the onset of puberty. After the onset of puberty, the negative feedback of ovarian steroid hormones becomes important to the regulation of gonadotropin release.     

钙对雌性大鼠去势后骨质疏松防治作用的研究

将１０周龄Ｗｉｓｔａｒ大鼠分为对照组（Ⅰ）及高钙组（Ⅱ），喂养７个月，测定骨密度（ＢＭＤ），骨矿物质及血清中有关内分泌激素，研究幼年及去势后补钙对骨质疏松的防治作用。结果Ⅱ组同Ⅰ组比：钙吸收率较低，去势后ＢＭＤ下降少，两组去势后ＢＭＤ的下降与去势前后的膳食含钙量呈负相关（ｒ分别为－０．７３６６，－０．８３１０），Ⅱ组的甲状旁腺素（ＰＴＨ）明显下降，骨断裂负荷与ＢＭＤ及骨钙密切相关（ｒ为０．６３４０、０．６８８１），证实大鼠自幼补钙以及去势后补充足量钙对预防去势后骨质疏松发生有一定的作用。