利骨素抗去卵巢大鼠骨矿物元素代谢紊乱的作用机制

通过测定骨元素含量和血清相关激素及白细胞介素-6水平,探讨了利骨素对去卵巢大鼠骨元素代谢的影响及其机制。将健康4月龄雌性SD大鼠24只随机分成3组:A组,假去卵巢组;B组,去卵巢组;C组,去卵巢+利骨素组。结果表明,去卵巢大鼠骨Ca、Mg、S、Mn、Zn等含量显著降低,P含量显著增加;应用利骨素可使去卵巢大鼠降低的骨Ca、Mg、S、Mn、Zn等含量显著回升,P含量显著回降。血清相关激素:去卵巢组较假去卵巢组大鼠,血清雌二醇(E2)、孕酮(P)、促甲状腺激素(TSH)、甲状腺素(T4)、降钙素(CT)、皮质醇(Cortisol)、生长素(GH)等含量降低,卵泡刺激素(FSH)、黄体生成素(LH)、白细胞介素-6(IL-6)等含量升高;去卵巢+利骨素组较去卵巢组,血清P,GH,Cortisol,TSH,T4等含量回升,LH含量回降。提示利骨素改变去卵巢大鼠体内相关激素水平是其纠正去卵巢大鼠骨元素代谢紊乱作用的重要机制。     

Ethanol Extract of Amomum tsao-ko Ameliorates Ovariectomy-Induced Trabecular Loss and Fat Accumulation

In Asia, Amomum tsao-ko has long been used as a spice or seasoning in food to stimulate digestion. In the present study, we evaluated the effects of ethanol extract of Amomum tsao-ko (EEAT) on menopausal osteoporosis and obesity. After the administration of EEAT in ovariectomy (OVX) mice models for five weeks, microcomputed tomography and a histological analysis were performed to assess, respectively, the trabecular structure and the fat accumulation in adipose, liver, and bone tissues. We also examined the effects of EEAT on a bone marrow macrophage model of osteoclastogenesis by in vitro stimulation from the receptor activator of nuclear factor-kappa Β ligand (RANKL) through real-time PCR and Western blot analysis. In addition, ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) with authentic standards was applied to characterize the phytochemical profiling of EEAT. We found that EEAT significantly decreased OVX-induced body weight gain and fat accumulation, significantly prevented OVX-induced deterioration of bone mineral density and microstructure of trabecular tissues, and significantly inhibited osteoclast differentiation by downregulating NF-κB/Fos/NFATc1 signaling in osteoclasts. Furthermore, UHPLC–MS/MS identified eight beneficial phytochemicals in EEAT. Collectively, these results suggest that EEAT might be an effective nutraceutical candidate to attenuate menopausal osteoporosis by inhibiting osteoclastogenesis and to prevent obesity by suppressing fat accumulation.     

Water Extract of Fritillariae thunbergii Bulbus Inhibits RANKL-Mediated Osteoclastogenesis and Ovariectomy-Induced Trabecular Bone Loss

Fritillariae thunbergii bulbus has been widely used to treat symptoms of coughs and airway congestion in the chest due to pathological colds and damp phlegm in traditional Chinese medicine. Despite its long history of traditional use, its pharmacological activities on osteoclastogenesis and osteoporosis have not been evaluated. This study investigated the effects of the water extract of Fritillariae thunbergii bulbus (WEFT) on osteoclast differentiation in bone marrow-derived macrophage cells and on ovariectomy (OVX)-induced osteoporosis in mice. We found that WEFT significantly inhibited osteoclastogenesis by downregulating the receptor activator of the NF-κB ligand (RANKL) signaling-induced nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. In an OVX-induced osteoporosis model, WEFT significantly prevented the OVX-induced trabecular loss of femurs, accompanied by a reduction in fat accumulation in the bone marrow and liver. In addition, WEFT significantly prevented weight gain and gonadal fat gain without recovering uterine atrophy. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, seven alkaloids (peimisine glucoside, yibeissine, peiminoside, sipeimine-glucoside, peimisine, peimine, and peiminine) were identified in WEFT. The results of this study suggest that WEFT can be a potential pharmacological candidate to reduce menopausal osteoporosis and menopause-related symptoms, such as fat accumulation.     

去卵巢合并单侧输尿管结扎诱导小鼠肾脏病变的研究

为研究去卵巢合并单侧输尿管结扎引起小鼠肾脏的病理变化及可能机制,选取C57BL/6J雌性小鼠为研究对象,分别设立对照组和模型组.手术3周后,取肾脏样本.使用HE,Masson’s Trichrome两种方法进行肾石蜡切片染色,通过RT-PCR技术检测肾纤维化相关因子TGF-β,CTGF,VEGF,fibronectin,炎症因子MCP-1,RANTES,肾素-血管紧张素系统(RAS)组分肾素(renin)、肾素受体(renin receptor)、血管紧张素原(AGT)的mRNA表达.结果显示,模型组小鼠肾小球萎缩,肾小管腔隙体积增加、膨大,肾小管间质纤维化.模型组小鼠肾脏fibronectin,MCP-1,RANTES的mRNA表达都显著上调,RAS组分renin receptor的基因表达显著上调.研究表明,去卵巢合并单侧输尿管结扎通过上调肾脏肾素受体表达,诱发肾脏纤维化与炎症反应.     

复方丹参合剂对去卵巢大鼠骨矿盐代谢的影响

用测定骨矿盐含量的方法,分析了复方丹参合剂(三种不同剂量)对切除双侧卵巢后的大鼠骨矿盐代谢的影响。将健康4月龄雌性SD大鼠36只,随机分成6组:A组(正常对照组);B组(假去卵巢组);C组(去卵巢组);D组(去卵巢 合剂小剂量组);E组(去卵巢 合剂中等剂量组);F组(去卵巢 合剂大剂量组)。去卵巢手术后1 d开始,连续用药11周。结果表明,去卵巢大鼠骨干质量、干质量/体质量、骨灰质量、骨灰质量/体质量、骨灰质量占骨干质量比等均明显降低,复方丹参合剂可使去卵巢大鼠降低的骨干质量、骨干质量/体质量、骨灰质量、骨灰质量/体质量、骨灰质量占骨干质量比等均显著回升。提示复方丹参合剂具有良好的对抗由于去卵巢引起骨矿盐含量降低和骨丢失作用。     

白藜芦醇对卵巢切除大鼠动脉血压及升压反应的影响

选用雌性Wistar大鼠,体重214.07±4.85 g,于双侧卵巢切除后分别皮下注射白藜芦醇RES(0.4 mg/kg)和17β-雌二醇EST(1 mg/kg)或等量溶媒芝麻油,以假手术大鼠作为对照.处理21天后,观察去势鼠及RES或EST替代治疗大鼠对血管紧张素Ⅱ、去甲肾上腺素、肾上腺素的升压反应以及压力感受性反射敏感性的变化.结果发现去势大鼠收缩压(SP)、舒张压(DP)和平均动脉压(MAP)明显升高,但皮下分别注射RES或EST后,SP,DP和MAP明显降低.去势鼠对AngⅡ,NA和Adr升压反应明显减弱,MAP的升高值明显减小.皮下注射RES或EST后,去势鼠对AngⅡ和NA敏感性均有不同程度的恢复,但皮下注射RES后,去势鼠对Adr的反应无明显改善.去势鼠颈动脉窦压力感受性反射的敏感性明显减弱,表现为其升压反射中MAP的升高明显低于假手术大鼠.结果表明去势鼠静息动脉血压升高,对升压剂AngⅡ,NA,Adr和颈动脉窦压力感受性反射的升压反应明显减弱.皮下分别注射EST结构类似物,即植物雌激素RES后,去势鼠对AngⅡ,NA和颈动脉窦压力感受性反射的升压反应与EST相似均有不同程度的恢复.     

碳酸钙对去卵巢大鼠骨元素代谢的影响

用测定骨元素含量的方法,分析了碳酸钙(CaCO3)对去卵巢大鼠骨元素代谢的影响。将健康4月龄雌性SD大鼠24只,用抽签法随机分成4组:正常对照组,假去卵巢组,去卵巢组,去卵巢 CaCO3组。去卵巢 CaCO3组大鼠于去卵巢手术后第2 d开始给予CaCO3灌胃,w(Ca)=20mg/kg,1次/d,持续11周。结果表明,去卵巢大鼠骨Ca、S、Mg、Mn等元素含量显著降低,Zn、Co含量降低,骨P含量增加;CaCO3可使去卵巢大鼠降低的骨Ca、S、Mg、Zn、Co、Mn等元素含量显著回升,骨P含量显著回降;CaCO3可纠正去卵巢大鼠的骨元素代谢紊乱。提示补钙防治骨质疏松是通过纠正骨矿物元素代谢紊乱而实现的。     

卵巢切除术对大鼠子宫内膜异位症的影响

目的：利用大鼠子宫内膜异位症动物模型,观察卵巢切除术对大鼠子宫内膜异位症的影响。方法：47只大鼠在建模后3周,第2次剖腹,观察移植物的生长情况和体积。将已成模大鼠随机分为两组：对照组（n＝23）和卵巢切除术组（n＝24）,对卵巢切除术组大鼠行双侧卵巢切除,分别观察两组动物成模后2、4、6和8周移植物的生长情况和体积。结果：与建模后3周时相比,成模后2、4、6和8周对照组大鼠移植物的生长情况和体积基本保持一致,而卵巢切除术组大鼠异位子宫内膜出现萎缩退化并且体积明显缩小,术后4、6和8周与术后2周相比,作用更明显,百术后4、6和8周之间无明显差异,术后8周仍可见异位内膜组织存在。组织学检查,对照组大鼠异位子宫内膜呈增生状态,而卵巢切除术组呈萎缩状态。结论：卵巢切除术可使子宫内膜异位症大鼠异位子宫内膜逐渐萎缩退化,但未能使其消失。     

Platinum nanoparticles reduce ovariectomy-induced bone loss by decreasing osteoclastogenesis

Platinum nanoparticles (PtNP) exhibit remarkable antioxidant activity. There is growing evidence concerning a positive relationship between oxidative stress and bone loss, suggesting that PtNP could protect against bone loss by modulating oxidative stress. Intragastric administration of PtNP reduced ovariectomy (OVX)- induced bone loss with a decreased level of activity and number of osteoclast (OC) in vivo. PtNP inhibited OC formation by impairing the receptor activator of nuclear factor-κB ligand (RANKL) signaling. This impairment was due to a decreased activation of nuclear factor-κB and a reduced level of nuclear factor in activated T-cells, cytoplasmic 1 (NFAT2). PtNP lowered RANKL-induced long lasting reactive oxygen species as well as intracellular concentrations of Ca(2+) oscillation. Our data clearly highlight the potential of PtNP for the amelioration of bone loss after estrogen deficiency by attenuated OC formation.     

大豆异黄酮对卵巢切除大鼠糖脂代谢和血清瘦素、抵抗素表达的影响

为探讨大豆异黄酮对卵巢切除大鼠糖脂代谢和血清瘦素、抵抗素表达的影响,将12周SD大鼠分成3组,假手术(Sham)组、卵巢切除(OVX)组和大豆异黄酮(OVX+Gen)组,每组7只,卵巢切除术后10 d,OVX组和Sham组大鼠每天腹腔注射生理盐水0.1 ml/只,OVX+Gen组每天注射大豆异黄酮0.2 mg/只,连续注射30 d后处死取血,检测子宫病理改变、血糖血脂和胰岛素水平、血清瘦素和抵抗素含量.结果发现卵巢切除后大鼠总胆固醇、HDL和LDL均增加(P<0.05),但胰岛素、血糖、甘油三酯、血清瘦素和抵抗素水平变化不明显(P>0.05);卵巢切除后补充大豆异黄酮,可促进子宫内膜上皮部分增生,但胰岛素、血糖、总胆固醇、甘油三酯、LDL和HDL、血清瘦素和抵抗素水平均无明显变化(与OVX组相比,P>0.05),结果提示大豆异黄酮对卵巢切除大鼠糖脂代谢参数和血清瘦素、抵抗素水平影响不大.