藏红花提取液对去卵巢大鼠骨密度及骨代谢生化指标的影响

目的:研究中药藏红花提取液对去卵巢大鼠股骨骨密度及血清骨代谢生化指标的影响。方法:选用48只4月龄SD雌性大鼠,随机分为6组:假手术组、模型组、戊酸雌二醇组、藏红花低、中、高剂量组。术后4周各组分别给予相应制剂灌胃,术后12周处死,分别测定股骨骨密度、子宫指数、雌二醇、血钙、血磷、碱性磷酸酶。结果:与模型组相比,藏红花各剂量组股骨骨密度明显升高(p<0.01),雌二醇测定值升高(p<0.01),碱性磷酸酶显著降低(p<0.01),血钙及血磷无统计学差异(p>0.05);与戊酸雌二醇组比较,藏红花各剂量组子宫指数显著降低(p<0.01)。结论:藏红花提取液有助于抑制去卵巢大鼠骨量的丢失,改善骨代谢,对骨质疏松症具有防治作用。     

藏红花提取液对去卵巢大鼠骨密度及骨代谢生化指标的影响

目的：研究中药藏红花提取液对去卵巢大鼠股骨骨密度及血清骨代谢生化指标的影响。方法：选用48只4月龄SD雌性大鼠,随机分为6组：假手术组、模型组、戊酸雌二醇组、藏红花低、中、高剂量组。术后4周各组分别给予相应制剂灌胃,术后12周处死,分别测定股骨骨密度、子宫指数、雌二醇、血钙、血磷、碱性磷酸酶。结果：与模型组相比,藏红花各剂量组股骨骨密度明显升高（p〈0.01）,雌二醇测定值升高（p〈0.01）,碱性磷酸酶显著降低（p〈0.01）,血钙及血磷无统计学差异（p〉0.05）;与戊酸雌二醇组比较,藏红花各剂量组子宫指数显著降低（p〈0.01）。结论：藏红花提取液有助于抑制去卵巢大鼠骨量的丢失,改善骨代谢,对骨质疏松症具有防治作用。     

Mechanisms of action of thyroid hormones in the skeleton

Background

Thyroid hormones regulate skeletal development, acquisition of peak bone mass and adult bone maintenance. Abnormal thyroid status during childhood disrupts bone maturation and linear growth, while in adulthood it results in altered bone remodeling and an increased risk of fracture

Scope of Review

This review considers the cellular effects and molecular mechanisms of thyroid hormone action in the skeleton. Human clinical and population data are discussed in relation to the skeletal phenotypes of a series of genetically modified mouse models of disrupted thyroid hormone signaling.

Major Conclusions

Euthyroid status is essential for normal bone development and maintenance. Major thyroid hormone actions in skeletal cells are mediated by thyroid hormone receptor α (TRα) and result in anabolic responses during growth and development but catabolic effects in adulthood. These homeostatic responses to thyroid hormone are locally regulated in individual skeletal cell types by the relative activities of the type 2 and 3 iodothyronine deiodinases, which control the supply of the active thyroid hormone 3,5,3’-L-triiodothyronine (T3) to its receptor.

General Significance

Population studies indicate that both thyroid hormone deficiency and excess are associated with an increased risk of fracture. Understanding the cellular and molecular basis of T3 action in skeletal cells will lead to the identification of new targets to regulate bone turnover and mineralization in the prevention and treatment of osteoporosis. This article is part of a Special Issue entitled Thyroid hormone signaling.     

Global analysis of gene expression in the estrogen induced pituitary tumor of the F344 rat

The F344 rat rapidly forms large prolactinomas in response to chronic estrogen treatment. To identify genes expressed in the course of this estrogen induced pituitary tumor growth, we performed microarray analysis on the F344 rat pituitary after chronic estrogen treatment and on untreated controls. At a significance level set to minimize type I error, some 72 genes were found to be differentially expressed between estrogen treated and untreated. Of those genes, 70 have not been reported previously as being affected by estrogen in the F344 rat pituitary. Since many other investigators have studied the effect of estrogen on specific gene expression in rat pituitary, we also examined the mRNA expression of the 36 genes that have been previously reported as having their expression affected by estrogen in the rat pituitary. Of these, 13 were found to have their expression affected by estrogen treatment in the same direction as had been reported by others.     

RGD多肽修饰钙磷陶瓷支架材料对骨质疏松兔成骨能力及骨功能影响的机制研究

摘要 目的：探究RGD多肽修饰钙磷陶瓷支架材料对骨质疏松（osteoporosis, OP）兔成骨能力和骨功能的影响极其可能的作用机制。方法：选取40只雌性SPF级新西兰大白兔,随机分为A组（正常对照组）和B组（OP组）,每组各20只,再将A组随机分为A1组：sham组、A2组：sham+HA组、A3组：sham+BCP组、A4组：sham+RGD-BCP组,每组5只;B组随机分为B1组：OP组、B2组：OP+HA组、B3组：OP+BCP组和B4组：OP+RGD-BCP组,每组5只。B组采用去势法制备OP模型,检测相关指标。结果：A组兔术前和术后3个月时BMD无变化（P>0.05）,B组兔术后3个月时的BMD值较术前下降（P<0.05）。自第4 d开始,A组和B组RGD-BCP支架材料组细胞的OD值高于HA和BCP支架材料（P<0.05）,且B组之间的差异较A组更大（P<0.05）。Western Blot分析显示,A、B两组中RGD-BCP中整合素avβ3的表达高于HA和BCP（P<0.05）,且B组之间的差异较A组更大（P<0.05）。B4和A4组p38 MAPK蛋白的相对表达均低于、Wnt5a和β-catenin表达均高于B2、B3和A2、A3组(P<0.05),此外,A4组p38 MAPK蛋白的相对低于、Wnt5a和?茁-catenin表达高于B4组(P<0.05)。结论：RGD-BCP对兔BMSCs具有良好的相容性和吸附作用,对OP模型兔更显著;且RGD-BCP的机制可能与调控p38 MAPK/Wnt5a/β-catenin信号通路有关,为OP合并骨缺损的修复提供了新的思路和理论依据。     

In vivo estrogen uptake by individual cell types of the rat anterior pituitary after short-term castration-adrenalectomy

Summary In vivo estrogen uptake was measured in five anterior pituitary cell types of the rat by a quantitative autoradiographic-immunocytochemical technique. In male and female rats that had been castrated and adrenalectomized for one day all five cell types showed nuclear concentration of label one hour after injection of ³H-estradiol. The order of labeling intensity was lactotropes > somatotropes > gonadotropes > corticotropes > thyrotropes. No significant overall sex difference in estrogen uptake was apparent although male pituitaries tended to take up slightly more. Physiological correlates to these data are discussed.Supported by PHS grant HD 12173 and Research Career Development Award HD 00243I wish to acknowledge Mr. Sing Kung Lau for his excellent technical assistance and Dr. P. Rodier for her advise and assistance with the statistical analysis. I also wish to thank Dr. A.F. Parlow and NIAMDD for antisera against rLH, hFSH, rPRL and rTSH and Dr. P. Petrusz, University of North Carolina, for antisera against bGH and h endorphin     

熊果酸对酒精性骨质疏松大鼠骨形成、骨矿化的影响

目的：探讨熊果酸对酒精所致骨质疏松大鼠骨形成、骨矿化的影响。方法：雄性Wistar大鼠60只,按体重随机分为空白对照 组、熊果酸对照组、模型组、熊果酸低、中、高剂量组,同时分别给予生理盐水、150 mg/kg 熊果酸、50%酒精,50 mg/kg 熊果酸,100 mg/kg 熊果酸,150 mg/kg 熊果酸灌胃。熊果酸对照组生理盐水剂量同空白组,熊果酸低、中、高剂量组酒精剂量同模型组。灌胃共 持续8 周。磷钼酸法检测血清磷(P)含量,比色法检测血清钙(Ca)含量,酶联免疫吸附（ELISA）法检测血清骨钙素(BGP)、骨形成蛋 白-2(BMP-2)浓度;HE 染色法观察股骨结构的病理学变化。结果：与空白对照组相比较,模型组血清BGP、BMP-2 和Ca、P 均明显 降低,且有统计学差异(P < 0.05),但熊果酸对照与空白对照组各项指标结果相近。熊果酸中、高剂量组大鼠血清BGP、Ca 和P 水 平均较模型组有显著升高,差异具有统计学意义(P < 0.05),但仅熊果酸高剂量组血清BMP-2 显著升高(P < 0.05)。股骨组织HE 染色结果显示,空白对照组骨小梁致密、规则且较粗,粗细均匀;模型组骨小梁稀松、不规则、粗细不均匀,甚至可见骨小梁断裂; 熊果酸中、高剂量组骨小梁致密、规则、较厚、粗细均匀,未见骨小梁断裂。结论：熊果酸能够促进酒精性骨质疏松大鼠的骨形成, 抑制骨矿物质的流失,在改善酒精致骨质疏松方面有一定的保护作用。     

The effect of the estrous cycle and estrogen on the release of immunoreactive alpha-melanocyte-stimulating hormone

Circulating levels and tissue content of alpha-MSH were measured on the morning of various days of the estrous cycle, and on the afternoon of proestrus in freely moving conscious rats. No surges of alpha-MSH were detected by RIA in the morning of various days of the cycle. The neurointermediate lobe content of alpha-MSH was slightly elevated on diestrus 1 as compared to the levels on diestrus 11 and proestrus but not to estrous levels. No changes in alpha-MSH content were detected in the anterior pituitary, the median eminence, mediobasal hypothalamus and the preoptic area at various stages of the estrous cycle. Plasma alpha-MSH levels were slightly elevated at 1500 hr of proestrus which was followed three hours later by a decline. This profile of plasma alpha-MSH on the afternoon of proestrus was reproduced by the SC administration of estradiol benzoate to long-term ovariectomized rats. These data suggest that, contrary to the results obtained by bioassay of alpha-MSH no surges of alpha-MSH occur on any day of the cycle, although a slight elevation on the afternoon of proestrus was detected. The altered pattern of release of this peptide on the afternoon of proestrus may be induced by estrogen.     

仙灵骨葆胶囊治疗骨质疏松疼痛患者的疗效及其对骨密度及骨代谢的影响

目的:探讨仙灵骨葆胶囊治疗骨质疏松疼痛患者的疗效,并分析其对骨密度及骨代谢的影响,为临床用药提供依据。方法:研究对象为我院2015年6月-2017年7月期间收治的60例骨质疏松症疼痛患者。根据治疗方案的不同将患者均分为对照组和观察组各30例。对照组患者采用常规西医治疗,观察组在对照组基础上加用仙灵骨葆胶囊治疗,两组均治疗6个月。治疗前及治疗6个月后(治疗后)采用视觉模拟量表(VAS)评分对患者的疼痛程度进行评价。评价并比较两组疗效。分别于治疗前、治疗后对所有患者腰椎、股骨颈骨密度以及血清N端中段骨钙素(N-MID)、骨钙素(BGP)以及I型胶原羧基末端交联肽(β-CTX)进行检测。结果:治疗后,观察组患者VAS评分明显低于对照组(P0.05),且观察组总有效率为93.33%(28/30),高于对照组的73.33%(22/30)(P0.05)。治疗后,两组患者腰椎、股骨颈骨密度均明显增加,且观察组患者腰椎骨密度明显高于对照组(P0.05)。治疗后,两组患者β-CTX水平均明显降低,BGP水平均明显升高,且观察组β-CTX水平明显低于对照组,而BGP水平明显高于对照组(P0.05),两组患者治疗前后N-MID水平均无明显变化(P0.05)。结论:仙灵骨葆胶囊治疗骨质疏松症疼痛患者疗效显著,能够减轻疼痛并改善骨密度及骨代谢。     

Studies on the mechanisms of the skeletal anabolic action of endogenous and exogenous parathyroid hormone

Parathyroid hormone (PTH) has been viewed as catabolic for bone. Nevertheless, exogenous PTH is anabolic when administered intermittently, at a frequency that permits complete clearance between doses. In the fetus and neonate, endogenous PTH is required for normal trabecular bone formation. In older animals PTH produces net bone loss in fulfilling its calcium homeostatic role, whereas PTH-related peptide (PTHrP), acting in a paracrine/autocrine mode, is anabolic. The proliferative, differentiating, and anti-apoptotic effects of PTH on cells of the osteoblast lineage leading to anabolism can be direct, or indirect via release of local growth factors. The anabolic effect of PTH is also influenced by osteoclastic activity such that suppression of osteoclasts with anti-resorptive agents, concomitant to administering PTH, may enhance the anabolic effect by delaying a reactive osteoclastic response. In contrast, prolonged suppression of osteoclast activity prior to administering PTH appears to diminish molecular signals that increase the osteoblast pool and thereby reduces the anabolic efficacy of PTH. These observations may define the proper timing of the use of PTH as a therapeutic in diseases of bone loss. Finally, the capacity of exogenous PTH to modulate extra-osseous factors such as 1,25 dihydroxyvitamin D may also modulate its potency as an anabolic agent.     

Changes in oxytocin content in the magnocellular neurons of the rat hypothalamus following water deprivation or estrogen treatment

Summary The effect of water deprivation or estrogen treatment on the oxytocin content of rat hypothalamic cells was examined using a quantitative immunohistological technique. Oxytocin-containing cells were visualized using the immunoperoxidase technique of Sternberger and a primary antiserum directed against oxytocin. The optical density of the darkest 3.2 m diameter spot in the cytoplasm of a cell was used as a measure of the oxytocin content of that cell. Water deprivation produced a significant decrease in anti-oxytocin staining in the anterior commissural nucleus of males and females. There was a similar decrease in the paraventricular nucleus of males, but not in the paraventricular nucleus of females or the supraoptic nucleus of either males or females. Estrogen treatment of ovariectomized female rats produced a fall in anti-oxytocin staining in the anterior commissural, but not paraventricular or supraoptic nuclei.     

雌激素和多巴胺对大鼠垂体组织中雌激素受体基因表达的影响

目的研究雌激素和多巴胺激动剂对雌激素受体在大鼠垂体组织表达的作用。方法20只成年雌性Wistar大鼠,切除卵巢后,随机分2组：（1）对照组（n=5）,皮下植入空白硅胶管;（2）雌激素组（n=15）皮下植入含有乙烯雌酚的硅胶管,8周后,两组各处死5只大鼠,雌激素组剩余大鼠（n=10）取出硅胶管,随机再分2组,安慰剂组（n=5）给予自来水灌胃,多巴胺组（n=5）给予溴隐亭（多巴胺激动剂）灌胃,用药4周后处死动物。放免法测定血清PRL水平,用反转录一聚合酶链反应（RT-PCR）方法检测ERs在各组垂体组织中的表达,以β-actin作为内参照,借助于计算机凝胶成像系统分析表达量。结果ERa,ERβ以及TERP在各组大鼠垂体组织均有表达,其中ERα和TERPmRNA水平在雌激素组明显高于对照组（P〈0．001）,在安慰剂组和多巴胺组的表达无明显差别。结论大鼠垂体组织中存在ER的表达,雌激素对ERα和TERP的表达具有升调节作用,多巴胺不影响雌激素受体的表达。     

The effect of oxytocin and fragment (MIF-I) on the development of tolerance to hypothermic and hypnotic action of ethanol in the rat

The daily pretreatment of rats with oxytocin (OXY) or MIF-I prior to ethanol (Et-OH) administration markedly altered the alcohol tolerance when tested on the fifth day of treatment. OXY (800 and 2400 nmole/kg SC) and MIF (800 nmole/kg SC) inhibited the development of tolerance to the hypnotic effect of Et-OH. MIF at this dose also inhibited the tolerance to the hypothermic effect. Only OXY in the dose of 800 nmole/kg suppressed hypothermia in an acute experiment with Et-OH and produced by itself hypothermia after acute administration (2400 nmole/kg). The tolerance to this last effect developed after four days of peptide treatment. The results indicate that OXY and MIF-I can influence the processes of development of tolerance to some central depressive effects of Et-OH in rats.     

The Influence of DNA Methylation on Bone Cells

DNA methylation in eukaryotes invokes heritable alterations of the of the cytosine base in DNA without changing the underlying genomic DNA sequence. DNA methylation may be modified by environmental exposures as well as gene polymorphisms and may be a mechanistic link between environmental risk factors and the development of disease. In this review, we consider the role of DNA methylation in bone cells (osteoclasts/osteoblasts/osteocytes) and their progenitors with special focus on in vitro and ex vivo analyses. The number of studies on DNA methylation in bone cells is still somewhat limited, nevertheless it is getting increasingly clear that this type of the epigenetic changes is a critical regulator of gene expression. DNA methylation is necessary for proper development and function of bone cells and is accompanied by disease characteristic functional alterations as presently reviewed including postmenopausal osteoporosis and mechanical strain.     

骨疏康胶囊联合唑来膦酸治疗老年骨质疏松症的临床疗效及对骨密度和骨代谢标志物的影响

摘要 目的：探讨骨疏康胶囊联合唑来膦酸治疗老年骨质疏松症（OP）的临床疗效及对骨密度和骨代谢标志物的影响。方法：根据随机数字表法将2019年2月~2022年3月期间我院收治的80例老年OP患者分为对照组（唑来膦酸治疗,40例）和研究组（骨疏康胶囊联合唑来膦酸治疗,40例）。对比两组疗效、骨密度、相关量表评分和骨代谢标志物水平情况,比较两组用药期间不良反应情况。结果：研究组（95.00%）的临床总有效率高于对照组（80.00%）,差异有统计学意义（P<0.05）。研究组治疗6个月后腰椎（L1～L4）骨密度、股骨颈骨密度高于对照组（P<0.05）。治疗6个月后两组VAS评分下降,ADL评分上升,且研究组变化较对照组大（P<0.05）。研究组治疗6个月后Ⅰ型前胶原N-端前肽（PINP）、骨钙素（BGP）、25-羟基维生素D[25-(OH)D]高于对照组,β-胶原羧基端肽（β-CTX）低于对照组（P<0.05）。两组不良反应发生率组间比较无统计学差异（P>0.05）。结论：骨疏康胶囊联合唑来膦酸治疗老年OP,可有效减轻疼痛症状,提高生活自理能力,可能与提高骨密度和调节骨代谢标志物水平有关,疗效较好。     

阿司匹林对体外培养骨髓基质细胞成骨性分化的影响

目的：探讨阿司匹林对骨髓基质细胞成骨性分化的影响。方法：培养SD大鼠骨髓基质细胞（BMSCs）,传代3次后进行成骨诱导分化,诱导培养基中加入不同浓度阿司匹林（0.5、1、2、5、10mmol/L）,同时设立对照组。采用cck-8法分析细胞增殖情况。比较阿司匹林组与对照组在细胞碱性磷酸酶（ALP）活性、骨钙素（OC）分泌量、钙结节染色等方面的成骨性差异。结果：阿司匹林无促进细胞增殖活性,而高浓度阿司匹林能够强烈抑制细胞增殖。0.5、1、2mmol/L浓度阿司匹林可促进BMSCs的成骨性分化,中低浓度组碱性磷酸酶含量、骨钙素分泌量在不同阶段显著高于对照组。14天茜素红染色可见中低浓度组钙结节数量高于对照组。结论：中低浓度阿司匹林作用于骨髓基质细胞可促进其成骨细胞特性表达,这表明阿司匹林有促进骨代谢合成的作用。     

阿司匹林对体外培养骨髓基质细胞成骨性分化的影响

目的:探讨阿司匹林对骨髓基质细胞成骨性分化的影响。方法:培养SD大鼠骨髓基质细胞(BMSCs),传代3次后进行成骨诱导分化,诱导培养基中加入不同浓度阿司匹林(0.5、1、2、5、10mmol/L),同时设立对照组。采用cck-8法分析细胞增殖情况。比较阿司匹林组与对照组在细胞碱性磷酸酶(ALP)活性、骨钙素(OC)分泌量、钙结节染色等方面的成骨性差异。结果:阿司匹林无促进细胞增殖活性,而高浓度阿司匹林能够强烈抑制细胞增殖。0.5、1、2mmol/L浓度阿司匹林可促进BMSCs的成骨性分化,中低浓度组碱性磷酸酶含量、骨钙素分泌量在不同阶段显著高于对照组。14天茜素红染色可见中低浓度组钙结节数量高于对照组。结论:中低浓度阿司匹林作用于骨髓基质细胞可促进其成骨细胞特性表达,这表明阿司匹林有促进骨代谢合成的作用。     

骨愈灵片联合依降钙素注射液对骨质疏松症患者Oswestry功能障碍指数评分及骨密度、骨代谢指标的影响

摘要 目的：探讨骨愈灵片联合依降钙素注射液对骨质疏松症患者Oswestry功能障碍指数（ODI）评分及骨密度、骨代谢指标的影响。方法：选择我院2018年3月~2021年2月间收治的骨质疏松症患者156例,采用随机数字表法分为对照组（采用依降钙素注射液治疗）和研究组（采用骨愈灵片联合依降钙素注射液治疗）,各为78例。观察两组疗效、不良反应,对比两组ODI评分、腰椎L2-L4、桡骨远端1/3处和股骨颈的骨密度、骨代谢指标[血钙 、血磷 、骨钙素（BGP）和β-胶原降解产物（β-CTX）]、炎性指标[促生长因子（IGF-1）、白介素-1（IL-1）、白介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）]水平。结果：研究组的临床总有效率明显高于对照组（P<0.05）。研究组治疗结束后ODI评分低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。研究组治疗结束后腰椎L2-L4、桡骨远端1/3处、股骨颈骨密度均大于对照组（P<0.05）。研究组治疗结束后血钙、BGP水平高于对照组,血磷、β-CTX水平低于对照组（P<0.05）。研究组治疗结束后IGF-1水平高于对照组,IL-1、IL-8、TNF-α水平低于对照组（P<0.05）。结论：骨质疏松症患者采用依降钙素注射液联合骨愈灵片治疗,可改善骨代谢和骨密度,调节炎性因子水平,促进机体功能恢复,疗效明确。     

降钙素对骨质疏松大鼠骨密度形态计量学与骨代谢的影响

目的探讨降钙素(密盖息)对骨质疏松大鼠骨密度、骨形态计量学影响以及与血钙、磷、维生素D代谢和生长因子的关系。方法用摘除大鼠双侧卵巢的方式制备骨质疏松模型(OVX),实验动物分为4个组:模型对照组、密盖息治疗组,盐酸雷洛昔芬治疗组,假手术组。应用HOLOGIC第4代双能X线4500W骨密度仪测定大鼠腰椎、股骨上段骨密度值(BMD);以骨形态计量学测股骨骨小梁面积、矿化沉积率;用ELISA法测定血清IGF-1水平和血清25OHVitD浓度以及血淋巴细胞维生素D受体(VDR)含量。结果密盖息治疗组、盐酸雷洛昔芬治疗组均较OVX组腰椎、股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。密盖息治疗组较盐酸雷洛昔芬治疗组股骨上段骨密度增高,两组之间差异有显著性(P<0.01)。密盖息治疗组骨小梁面积明显增加、矿化沉积率增高。密盖息治疗组、盐酸雷洛昔芬治疗组血清IGF-1浓度值、血清25-OHVitD浓度值升高,与OVX组比较差异有显著性(P<0.01)。各组血淋巴细胞VDR含量无明显变化,与OVX组比较差异无显著性(P>0.05)。结论密盖息能够预防腰椎、股骨上段骨密度丢失,使骨小梁面积明显增加、矿化沉积率增高并且血清IGF-1及血清25-OHVitD浓度值升高,但对VDR含量无明显作用。