普伐他汀对去势大鼠BMP-2表达及成骨细胞增殖的影响

目的研究普伐他汀治疗去势大鼠骨质疏松症的疗效，并探讨其作用机制。方法取12周龄的雌性Wistar大鼠40只，氯氨酮（5mg／100g）麻醉条件下．其中30只打开腹腔去除双侧卵巢，逐层缝合，另10只予以单纯打开腹腔不切除卵巢。将大鼠分为A组（模型组）、B组（治疗组）、C组（阳性对照组）、D组（假手术组）4组，饲养12周后，分别予以生理盐水（10ml／kg）、普伐他汀水溶液（2mg／kg）、α-D3水溶液（0．05μg／kg）及生理盐水（10ml／kg）灌胃。灌胃12周后，处死各组动物，取右胫骨上端做病理切片，通过HE染色对成骨细胞等进行观察比较；骨形态发生蛋白2（BMP-2）免疫组化染色观察。结果经过12周的普伐他汀水溶液灌胃治疗，明显增加成骨细胞数量（P〈0．05），而且通过免疫组化染色发现有BMP-2的棕色深染，阳性细胞比例明显高于模型组（P〈0．01）。结论普伐他汀可促进成骨细胞增殖、分化，其治疗骨质疏论症的机制是通过提高BMP-2的表达来实现的。     

女贞子对去卵巢大鼠钙代谢及维生素D依赖型基因表达的影响

目的研究补肾中药女贞子对去卵巢大鼠钙代谢及维生素D依赖型基因表达的影响。方法大鼠去卵巢手术处理4周后,ig给药治疗14周。血清、尿液及粪便中钙水平采用比色法测定。RT-PCR技术分析小肠及肾脏基因表达。结果大鼠去卵巢后体内钙流失显著增加,表现在血钙下降,尿钙及粪钙排泄增加。女贞子可以有效防止尿钙及粪钙排泄增加,并恢复血钙水平。RT-PCR分析表明雌二醇和女贞子都可以抑制去卵巢引起的小肠维生素D受体(VDR)mRNA表达下降。女贞子对肾脏25-羟基维生素D 1-羟化酶(1-OH ase)及25-羟基维生素D 24-羟化酶(24-OH ase)mRNA无明显作用,但却可以提高肾脏钙结合蛋白-9k(C aBP-9k)及钙结合蛋白-28 k(C aBP-28k)的基因表达。结论女贞子能够改善雌激素缺乏所引起的钙失衡状态,主要是通过提高小肠对活性维生素D的敏感性及加强肾脏对钙的重吸收而发挥作用的。     

Comparison of chemical compositions and osteoprotective effects of different sections of velvet antler

Ethnopharmacological relevance

Velvet antlers (VA) have been claimed for centuries to have numerous medical benefits including strengthen bones. To investigate and compare the anti-osteoporotic activities from different sections of VA.

Materials and methods

Fresh VA prepared from farmed sika deers (Cervus nippon) was divided into upper (VAU), middle (VAM), and basal (VAB) sections. The chemical constituents and anti-osteoporotic effect of different sections from VA were evaluated using ovariectomized rats.

Results

Levels of water-soluble extracts, diluted alcoholic extract, amino acids, testosterone, insulin-like growth factor (IGF)-1and testosterone plus estradiol significantly differed among the different sections. Levels of these constituents were significantly higher in the upper section than in the basal section. Moreover, levels of testosterone and IGF-1 of the VAM were also significantly higher than those of the VAB. Calcium level increased downward from the tip with statistical significance. The strength of vertebrae increased in all VA-treated groups compared to the control, but only treatment with VAU and VAM increased the strength of the femur and the microarchitecure of the trabecular bone. Alkaline phosphatase levels of VAU- and VAM-treated groups significantly decreased, but osteocalcin did not significantly change. Moreover, VAU and VAM dose-dependently increased proliferation and mineralization of MC3T3-E1 cells.

Conclusion

Our study provides strong evidence for the regional differences in the effectiveness of velvet antler in treating osteoporosis. However, further studies are needed to elucidate the bioactive chemical constituents associated with the anti-osteoporotic effects of velvet antler.     

Anti-osteoporotic effect of Erythrina variegata L. in ovariectomized rats

The present study was designed to investigate whether Erythrina variegata L. (EV), which belongs to the leguminous family, exerted any beneficial effects on bone in ovariectomized rats. Daily oral administration of the EV extract at 300 and 600 mg/kg for 14 weeks to rats prevented the OVX-induced increase in the serum OCN, ALP, and urinary DPD levels. Histomorphometric analysis of the proximal end of the tibia showed that the EV extract prevented the estrogen deficiency-induced decrease in trabecular thickness and trabecular area, as well as restoring the increase in trabecular separation in a dose-dependent manner. Moreover, the EV extract improved the energy absorption and stiffness of the mid-shaft of the rat femur. Thus, the present study clearly demonstrated that EV could suppress the high rate of bone turnover induced by estrogen deficiency, inhibit bone loss and improve the biomechanical properties of bone in the OVX rats.     

重组人生长激素对去势大鼠正畸牙牙周组织改建的影响

目的:探讨重组人生长激素(recombinanthumangrowthhormone,rh-GH)对去势(ovariectomy,OVX)大鼠正畸牙移动后牙周组织细胞变化的影响。方法:30只7周龄SPF级雌性Wistar大鼠随机分为3组:对照组、去势盐水组(OVX-NS组)和去势生长激素组(OVX-GH组)。将去势摘除双侧卵巢和腹部皮下注射rh-GH作为不同处理因素,观察第15天和第30天时3组大鼠正畸牙移动引起牙槽骨受压侧破骨细胞数的变化,并进行组织学观察。用SPSS12.0软件包对数据进行完全随机设计资料的方差分析。结果:对3组大鼠不同时间正畸牙牙槽骨受压侧破骨细胞计数进行比较,发现同一时间3组数据的差异有统计学意义(P<0.05);OVX-NS组比OVX-GH组显著增多(P<0.05),对照组最少;同组相比,第15天处死的大鼠与第30天处死的大鼠其破骨细胞数无显著差异(P>0.05);牙周组织学观察见,OVX-GH组牙周膜的损伤和创伤性炎症较OVX-NS组明显减轻。结论:去势(成年)大鼠腹部皮下注射rh-GH,能够减少其正畸牙移动引起的受压侧破骨细胞数目,同时可促进牙周组织因正畸力所致的病理性变化的恢复,对成年正畸治疗有良好的协同作用。     

蛇床子总黄酮对去卵巢骨质疏松大鼠股骨骨密度及生物力学的影响

目的探讨蛇床子总黄酮对去卵巢（OVX）骨质疏松大鼠股骨骨密度及股骨生物力学的影响。方法40只6、7月龄雌性SD大鼠随机分为4组：假手术（SHAM）组,去卵巢（OVX）组,OVX＋已烯雌酚（E）组和OVX＋蛇床子总黄酮组,每组10只。实行手术后,于术后第三天开始灌胃用药。90天后处死大鼠,取左测股骨进行股骨骨密度和股骨生物力学的测量。结果去卵巢后股骨骨密度及股骨生物力学指标明显下降;用蛇床子总黄酮后,股骨骨密度及股骨生物力学指标均增高。结论蛇床子总黄酮对去卵巢（OVX）造成的骨质疏松有一定的防治作用,能防止骨生物力学性能的受损,效果略逊色于已烯雌酚。     

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral,microarchitectural, biomechanical and matrix properties of rat bone

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid–postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized–steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below −2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.     

Placenta Hominis Protects Osteoporosis in Ovariectomized Rats

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T₄) level was stimulated in OVX rats. The extracts inhibited the T₄ level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.     

Tualang honey supplement improves memory performance and hippocampal morphology in stressed ovariectomized rats

Recently, our research team has reported that Tualang honey was able to improve immediate memory in postmenopausal women comparable with that of estrogen progestin therapy. Therefore the aim of the present study was to examine the effects of Tualang honey supplement on hippocampal morphology and memory performance in ovariectomized (OVX) rats exposed to social instability stress. Female Sprague-Dawley rats were divided into six groups: (i) sham-operated controls, (ii) stressed sham-operated controls, (iii) OVX rats, (iv) stressed OVX rats, (v) stressed OVX rats treated with 17β-estradiol (E2), and (vi) stressed OVX rats treated with Tualang honey. These rats were subjected to social instability stress procedure followed by novel object recognition (NOR) test. Right brain hemispheres were subjected to Nissl staining. The number and arrangement of pyramidal neurons in regions of CA1, CA2, CA3 and the dentate gyrus (DG) were recorded. Two-way ANOVA analyses showed significant interactions between stress and OVX in both STM and LTM test as well as number of Nissl-positive cells in all hippocampal regions. Both E2 and Tualang honey treatments improved both short-term and long-term memory and enhanced the neuronal proliferation of hippocampal CA2, CA3 and DG regions compared to that of untreated stressed OVX rats.     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.