Response of trabecular bone,thyroid C and follicular cells to synthetic salmon calcitonin in middle‐aged orchidectomized male rats

In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C‐cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT‐ and TH‐producing thyroid cells in orchidectomized (Orx) middle‐aged rats. Twenty‐four male Wistar rats aged 15 months were randomly divided into Orx and sham‐operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx + CT; 100 IU kg⁻¹ b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public‐domain image‐processing program. The peroxidase–antiperoxidase method was applied for localization of CT in C‐cells. Anti‐human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT‐immunopositive thyroid C‐cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T₄), and calcium (Ca²⁺) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C‐cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the V_V of the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T₄ and urinary Ca²⁺ concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C‐cells and changes the structure of the thyroid gland, indicating hypoactivity.     

Tamoxifen stimulates calcitonin-producing thyroid C-cells and prevents trabecular bone loss in a rat model of androgen deficiency

Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an inhibitor of bone resorption. In this study, we investigated the effects of tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells, trabecular bone and biochemical markers of bone metabolism in an animal model of androgen deficiency, represented by middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO) groups. Rats from one Orx group were injected subcutaneously with TAM citrate (Orx + TAM; 0.3 mg kg⁻¹ b.w.), while the rats from SO and a second Orx group received vehicle alone, once a day for 3 weeks. The peroxidase–antiperoxidase method was applied for localization of CT in C-cells. Thyroid C-cells were morphometrically and ultrastructurally analyzed. An ImageJ image-processing program was used to measure bone histomorphometric parameters. Blood serum samples were analyzed for CT, osteocalcin (OC), calcium (Ca²⁺) and phosphorus (P). Urinary Ca²⁺ concentrations were measured. TAM treatment significantly increased thyroid C-cell volume (V_c) and serum CT when compared with vehicle-treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed that administration of TAM significantly increased cancellous bone area, trabecular thickness and trabecular number, whereas trabecular separation was significantly decreased compared with vehicle-treated Orx rats. Serum OC and urinary Ca²⁺ concentrations were significantly lower in comparison with the control Orx group. These results indicate that in our rat model of androgen deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased trabecular bone mass.     

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone‐sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT ) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C‐cells. Fifteen‐month‐old Wistar rats were either bilaterally orchidectomized (Orx) or sham‐operated (SO ). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg^?1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C‐cells by immunohistochemical staining for thyroglobulin and CT . Thyroid follicular epithelium, interstitium, colloid and CT ‐immunopositive C‐cells were examined morphometrically. Serum concentrations of osteocalcin (OC ), triiodothyronine (T₃), thyroxine (T₄) and CT were determined as well as urinary calcium (Ca²⁺) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P  < 0.05), but trabecular separation (Tb.Sp) was decreased (P  < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P  < 0.05) compared with Orx, whereas Vv of the colloid was lower (P  < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC , T₃, T₄ and urinary Ca²⁺ concentrations (P  < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.     

Influence of ferutinin on bone metabolism in ovariectomized rats. II: Role in recovering osteoporosis

The aim of the present investigation, which represents an extension of a previous study, was to investigate the effect of ferutinin in recovering severe osteoporosis due to estrogen deficiency after rat ovariectomy and to compare phytoestrogen effects with those of estrogens commonly used in hormone replacement therapy (HRT) by women with postmenopausal osteoporosis. The animal model used was the Sprague–Dawley ovariectomized rat. Ferutinin was orally administered (2 mg kg⁻¹ per day) for 30 or 60 days starting from 2 months after ovariectomy (i.e. when osteoporosis was clearly evident) and its effects were compared with those of estradiol benzoate (1.5 μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized (OVX) and sham-operated (SHAM) rats. Histomorphometric analyses were performed on trabecular bone of lumbar vertebrae (4th and 5th) and distal femoral epiphysis, as well as on cortical bone of femoral diaphysis. Bone histomorphometric analyses showed that ferutinin seems to display the same effects on bone mass recorded with estradiol benzoate, thus suggesting that it could enhance the recovery of bone loss due to severe estrogen deficiency in OVX rats. On this basis, the authors propose listing ferutinin among the substances representing a potential alternative for the treatment of postmenopausal osteoporosis, which occurs as a result of estrogen deficiency.     

睾丸酮对雄性大鼠类固醇性骨质疏松的影响

目的探讨睾丸酮对雄性大鼠类固醇性骨质疏松的影响。方法30只3月龄雄性SD大鼠,随机分成对照组(A组)、泼尼松组(B组)、睾丸酮(C组)。A组灌生理盐水(4mL·kg-1·d-1),B组予醋酸泼尼松灌胃(4mg·kg-1·d-1),C组灌胃给予甲睾酮(0.2mg·kg-1·d-1)+醋酸泼尼松(4mg·kg-1·d-1),共90d。实验结束后,处死全部大鼠取腰椎和胫骨上段进行不脱钙骨包埋切片,应用计算机自动图像分析系统进行骨组织形态计量学分析。结果与泼尼松组比较,胫骨上端松质骨的%Tb.Ar增加了108%(P<0.01),Tb.N增加了96%(P<0.05),Tb.Sp减少60%;BFR/TV增加了172%(P<0.05),Oc.N减少40.7%(P<0.05);腰椎松质骨的%Tb.Ar增加了52.4%(P<0.05),Tb.Th增加了42%(P<0.05),Tb.Sp减少20%(P<0.05),MAR增加26%(P<0.05)。结论睾丸酮可以有效阻止泼尼松所引起的骨骨质丢失,维持正常的骨质结构。     

Soy Phytoestrogens Do Not Fully Reverse Changes in Rat Pituitary Castration Cells: Unbiased Stereological Study

The aim of the study was to examine the potential of the principal soy isoflavones, genistein and daidzein, or isoflavone rich soy extract to recover pituitary castration cells in orchidectomized adult male rats in comparison with the effects of estradiol. Two weeks post orchidectomy (Orx), animals received estradiol‐dipropionate, genistein, daidzein or soy extract subcutaneously for 3 weeks. Control sham‐operated (So) and Orx rats received just the vehicle. Changes in the volumes of pars distalis, of individual follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) containing cells, their volume, numerical density and number were determined by unbiased design‐based stereology. The intracellular content of βFSH and βLH was estimated by relative intensity of fluorescence (RIF). Orchidectomy increased all examined stereological parameters and RIF. Compared to Orx, estradiol increased the volume of pars distalis, but reversed RIF and all morphometric parameters of gonadotropes to the level of So rats, except their number. Treatments with purified isoflavones and soy extract decreased RIF to the control So level, expressing an estradiol‐like effect. However, the histological appearance and morphometrical features of gonadotropes did not follow this pattern. Genistein increased the volume of pars distalis, decreased the volume density of LH‐labeled cells and raised the number of gonadotropes. Daidzein decreased the cell volume of gonadotropic cells but increased their number and numerical density. Soy extract induced an increase in number and numerical density of FSH‐containing cells. Therefore, it can be concluded that soy phytoestrogens do not fully reverse the Orx‐induced changes in pituitary castration cells. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.     

卵巢切除及雌二醇对大鼠腰椎松质骨微结构的作用及其生物力学性能的分析

应用micro-CT获得腰椎松质骨微结构的三维参数,分析卵巢切除术与雌二醇干预对大鼠松质骨微结构及整体骨生物力学性能的作用,初步讨论松质骨微结构的改变对生物力学性能的影响.6月龄未交配雌性SD大鼠30只,随机分成3组(每组10只):假手术对照组(Sham)、去卵巢组(OVX)和去卵巢 补充雌二醇组(EBT).术后相同条件饲养5个月,取第3腰椎进行生物力学压缩试验,第4腰椎行micro-CT扫描.结果表明,与相应的Sham组比较,OVX组的BV/TV、Tb.N均明显下降,Tb.Sp和SMI明显增高.EBT组的BV/TV、Tb.N和Tb.Th均大于OVX组,Tb.Th和SMI明显小于OVX组.骨力学性能检测显示OVX组腰椎松质骨E、Fmax和σmax均明显降低,而EBT组上述骨生物力学参数均明显改善.通过micro-CT获得的骨微结构参数并结合骨力学性能检测能为合理评价骨质疏松及抗骨质疏松药物药效研究提供较好的实验依据.     

脊髓损伤早期及制动大鼠股骨干骺端的显微CT观察

背景：脊髓损伤后可引起损伤平面以下骨量大量丢失,导致骨质疏松。 目的：观察比较脊髓损伤及失用性制动模型大鼠股骨远端骨密度及骨微观结构的改变。 方法：将SD大鼠随机分为3组：对照组,切除T10椎板,不损伤硬膜及脊髓;脊髓损伤组,切除T10椎板后行Allen's法造成脊髓损伤;制动组,以大鼠双侧腿－尾缝合造成双下肢制动。10 d后取一侧尺、桡骨及股骨行骨密度检测,另一侧股骨行显微CT扫描。 结果与结论：脊髓损伤组与制动组大鼠股骨远端骨密度、骨矿物质含量、骨体积分数表、骨小梁厚度、骨皮质面积及厚度、骨小梁数量均低于对照组(P < 0.05 ),骨小梁结构模型指数、骨表面积体积比、骨小梁分离度均高于对照组;脊髓损伤组上述指标较制动组变化程度更显著(P < 0.05)。3组尺、桡骨密度差异无显著性意义。说明脊髓损伤及制动均可导致骨量丢失,在脊髓损伤早期损伤平面以下部位骨微观结构呈现骨质疏松明显改变,且程度比失用性因素严重。     

Immunoreactive TSH cells in juvenile and peripubertal rats after estradiol and human chorionic gonadotropin treatment

Different hormones and growth factors control the homeostasis of the anterior pituitary gland. We examined the morphological features of pituitary thyroid stimulating hormone (TSH)-producing cells in juvenile and peripubertal female rats after treatments with estradiol-dipropionate (EDP), human chorionic gonadotropin (hCG) and a combination of both hormones (EDP+hCG). TSH-producing cells were labelled using a peroxidase-antiperoxidase immunohistochemical procedure for binding of a rabbit anti-rat beta-thyrotropic polyclonal antisera. Morphometric differences in the cytoplasmic and nuclear volume densities in thyrotropes after the treatments were determined using a stereological method. The relative weights of the pituitary glands were significantly higher in the EDP- and EDP+hCG-treated juvenile and peripubertal rats than in untreated age-matched controls. Treatment with EDP promoted a decrease, and treatment with hCG an increase, of the cellular and nuclear volumes in TSH cells in both juvenile and peripubertal females in comparison with the respective controls. Treatment with a combination of EDP+hCG did not induce any significant changes. The cytoplasmic and nuclear volume densities in TSH cells in the EDP+hCG-treated group were significantly higher than in the EDP-treated, and significantly lower than in hCG-treated rats at both growth stages. These findings suggest that estradiol and hCG exerted opposite effects on pituitary TSH-immunoreactive cells. The observed effects on thyrotrope morphology were apparently independent of the stage of development.     

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E₂; 5 µg·100 g⁻¹·day⁻¹) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E₂ treatment caused an increase in uterine weight. Although E₂ administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E₂-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.     

雷公藤甲素通过抑制破骨细胞生成预防骨丢失的研究

目的 探讨雷公藤甲素抗骨质疏松的作用及机制。方法 建立大鼠老年性骨质疏松模型。40只22月龄雄性SD大鼠随机分为雷公藤甲素（每天15μg/kg腹腔注射）治疗组和生理盐水对照组（每天15μg/kg腹腔注射）,连续8周。采用显微CT分析胫骨近端骨松质的骨密度(BMD)和骨显微结构。WB检测成骨相关蛋白表达水平。TRACP-5b染色法测定破骨细胞数,同时检测骨吸收标志物表达水平。结果 显微CT结果显示,雷公藤甲素治疗组大鼠骨密度、骨体积/总体积比值(Bv/Tv)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)、骨小梁间距(Tb.Sp)均显著高于对照组（P<0.05）。两组的成骨相关蛋白表达水平无明显差异,TRACP-5b染色显示雷公藤甲素减少了体内破骨细胞的数量（P<0.05）,同时血液骨吸收标志物水平也明显降低（P<0.05）。结论 雷公藤甲素通过抑制破骨细胞生成进而对老年性骨质疏松有保护作用。雷公藤甲素可能是治疗老年性骨质疏松症的一种可行方案。     

"Oxidative stress": effects of mild endurance training and testosterone treatment on rat gastrocnemius muscle

We evaluated the effects of testosterone overload on mitochondrial superoxide dismutase (MnSOD), cytochrome oxidase (COX) and citrate synthase (CS) activities of the rat superficial gastrocnemius both in non-exercised muscle and following moderate endurance training. Basal (bLPO) and stimulated (sLPO) lipid peroxidation was measured as an index of oxidative tissue damage. Furthermore, to assess the relationship between exercise and testosterone-induced metabolic adaptations and contractile protein expression, the distribution of myosin heavy chain (MHC) isoforms was analysed by SDS-PAGE. Samples were obtained from: controls (C), rats treated with testosterone propionate (Tp) (TP, 5 mg kg^–1 i.m. 6 days/week), trained rats (E, 5 days/week) and rats trained and treated with Tp (ETP). MnSOD significantly increased in E and TP in comparison with C and ETP. Training induced a significant increase in COX activity both in E and ETP whereas a statistical reduction was observed in TP in comparison with the other groups. Moreover, testosterone administration was associated with a significant reduction in CS activity which significantly increased in ETP. A reduction in lipid peroxidation was observed in E and ETP in comparison with controls both in basal and stimulated conditions, whereas TP showed a significant increase of bLPO. In trained rats enzymatic changes were correlated with an increase in the proportion of fast oxidative MHC-2A and MHC-2X with decrease of the proportion of fast MHC-2B. In contrast, Tp treatment induced an increase in the proportion of MHC-2B whereas MHC-2A and MHC-2X disappeared. Finally, ETP showed a reduction in MHC-2B and an increase in MHC-1 and MHC-2X. These data suggest that testosterone supplementation seems not to significantly modify the metabolic adaptation induced by exercise in gastrocnemius muscle. Furthermore, testosterone overload to non-exercised rats seems to reduce the mitochondrial function and increase the lipid peroxidation of the muscle. Electronic Publication     

Angiogenic and Tissue Remodeling Factors in the Prostate of Elderly Rats Submitted to Hormonal Replacement

The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague–Dawley rats were separated into one Young group (4‐months old), treated with peanut oil (5 mL kg^?1, s.c.), and six Senile groups. The senile rats (10‐months old) were subdivided into: Senile group (SEN) (5 mL kg^?1 peanut oil, s.c.); Testosterone group (TEST) (5 mg kg^?1 testosterone cipionate, s.c.); Estrogen group (EST) (25 µg kg^?1 17β‐estradiol, s.c.); castrated group (CAS) (surgical castration); castrated‐testosterone group (CT) (same treatment as CAS and TEST groups); and castrated‐estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin‐like growth factor‐1 receptor (IGFR‐1), matrix metalloproteinase‐9 (MMP‐9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR‐1 and MMP‐9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders. Anat Rec, 296:1758–1767, 2013. © 2013 Wiley Periodicals, Inc.     

海藻酸多糖衍生物治疗大鼠骨质疏松

背景：作者既往研究发现海藻酸多糖衍生物有促进骨细胞生长的作用。 目的：探索海藻酸多糖衍生物治疗骨质疏松的效果。 方法：60只Wistar雌性大鼠随机分成对照组,治疗组和模型组,每组20只。治疗组和模型组大鼠用维甲酸诱导产生骨质疏松模型。治疗组大鼠每只每公斤每天10 mg多糖衍生物灌胃,模型组每只每公斤每天10 mg葡萄糖灌胃,持续2周。观察大鼠股骨病理形态学和骨组织形态计量学变化。 结果与结论：与对照组相比,模型组大鼠股骨骨小梁面积、平均骨小梁厚度、骨小梁密度显著降低,而髓腔质间隔宽度则明显增加;经过海藻多糖衍生物治疗后,治疗组大鼠股骨平均骨小梁密度,平均骨小梁厚度和骨小梁面积较模型组均显著上升,同时髓腔质间隔宽度明显下降;说明海藻酸性多糖能有效促进骨细胞生长,可治疗和预防骨质疏松。     

Progesterone,estradiol, testosterone and dihydrotestosterone: Effects on rate of extinction of a conditioned taste aversion in rats

An investigation was made to determine why the prolonged rate of extinction of a conditioned taste aversion induced by testosterone is diminished when the ovarian system is intact. In the first experiment, 36 gonadectomized female rats received injections of progesterone, testosterone propionate (TP), progesterone plus TP, or sesame oil. Progesterone did not reduce the slow extinction rate induced by TP. In a second experiment, 36 gonadectomized female rats received injections of estradiol dipropionate (EP), TP, EP plus TP, or sesame oil. Estradiol dipropionate reduced the effectiveness of TP in prolonging the extinction rate. These same results (the ineffectiveness of progesterone and the effectiveness of EP in blocking TP-induced slow extinction) were also observed in male rats in a third experiment. Dihydrotestosterone, as well as testosterone, has been shown to prolong extinction: hence, in a fourth experiment 30 gonadectomized female rats received injections of EP, TP, dihydrotestosterone propionate (DHTP), EP plus DHTP, or sesame oil. Estradiol dipropionate reduced the DHTP-induced slow extinction. All the above data are consistent with the hypothesis that it is estradiol from the ovaries that diminishes the effect of testosterone on the rate of extinction of a conditioned taste aversion in intact females.     

康力龙、泼尼松对大鼠骨组织形态学的影响

目的　探讨康力龙和泼尼松对大鼠骨组织形态学的影响。方法　 3月龄雄性SD大鼠 2 4只 ,体重 2 31 7± 33 3g随机分为三组。分别用蒸馏水、泼尼松 4 5mg·kg-1·d-1(每周二次 )和泼尼松 4 5mg·kg-1·d-1加康力龙 0 5mg·kg-1·d-1灌胃(每周 6次 ) ,持续 90天。用图像分析仪测算胫骨近端骨小梁的骨形态计量学指标 ,并在扫描电镜下观察大鼠腰椎的组织结构改变。结果　与对照组比较 ,泼尼松组大鼠胫骨的骨吸收增加 (破骨细胞数 + 92 % ) ,骨小梁间隙 (Tb .Sp)增宽 187% ,骨形成率(BFR/TV)减少 89% ,骨小梁面积 (%Tb .Ar)减少 (- 5 8% )。腰椎的骨小梁变少 ,变细 ,断裂 ,连接不紧密 ,表面常见骨吸收形成的陷窝。与泼尼松组比较 ,康力龙组骨形成增加 (BFR/TV + 75 2 % ) ,骨吸收减少 (破骨细胞数 - 41% ) ,骨量增加 (%Tb .Ar +87% ,Tb .Sp - 5 8% )。腰椎的骨小梁粗大 ,排列整齐 ,连接紧密。结论　长期使用泼尼松可导致骨质疏松 ,康力龙对此有防止作用。     

骨质疏松与骨关节炎患者松质骨的显微结构

目的:通过显微计算机断层扫描(micro-computed tomography,Micro-CT)检测股骨头松质骨显微结构,研究骨质疏松与骨关节炎的关系。方法:绝经后妇女骨质疏松性股骨颈骨折和原发性髋关节骨关节炎患者各20名,以Micro-CT扫描检测股骨头软骨下松质骨标本,对2组患者的松质骨显微结构参数进行比较。结果:骨质疏松与骨关节炎松质骨显微结构参数:骨体积分数(bone volume fraction,BV/TV)、骨表面积体积比(bone surface/bone volume,BS/BV)、骨小梁厚度(trabecular thickness,Tb.Th)、骨小梁间距(trabecular separation,Tb.Sp)、结构模型指数(structure model index,SMI)、连接密度(connectivity density,Conn.D)比较差异有统计学意义,BV/TV,SMI与Tb.N,TbTh,BS/BV,Tb.Sp呈相关关系。结论:骨质疏松与骨关节炎的显微结构存在差异,这些差异可能导致相反的骨缺陷;BV/TV,SMI是评价显微结构参数的2个重要指标。     

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.     

Protective Effects of Annona Muricata Linn. (Annonaceae) Leaf Aqueous Extract on Serum Lipid Profiles and Oxidative Stress in Hepatocytes of Streptozotocin-Treated Diabetic Rats

Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as ‘control’ animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs'' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg⁻¹). Group C rats were additionally treated with AME (100 mg kg⁻¹ day⁻¹, p.o.) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg⁻¹ day⁻¹ p.o.) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg⁻¹ i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (p<0.05) CAT, GSH, SOD, GSH-Px activities, and HDL levels. AME-treated Groups C and D rats showed significant decrease (p<0.05) in elevated blood glucose, ROS, TBARS, TC, TG and LDL. Furthermore, AME treatment significantly increased (p<0.05) antioxidant enzymes'' activities, as well as serum insulin levels. The findings of this laboratory animal study suggest that A. muricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants.     

自拟补肾活血颗粒对去卵巢骨质疏松症大鼠的治疗作用

目的:观察自拟补肾活血颗粒(MBHG)对去卵巢大鼠骨质疏松症的治疗作用。方法:雌性SD大鼠,随机取10只作为假手术组(sham组),其余大鼠制备去卵巢骨质疏松症,随机分为:模型(model)组;补肾活血颗粒高(200 mg/kg)、中(100 mg/kg)、低(50 mg/kg)剂量组;阳性对照组(戊酸雌二醇组)。每组10只,连续灌胃给药12周。观察大鼠骨小梁形态,测量骨小梁的面积、厚度、间距及面积百分数,全自动分析仪检测血清中钙、磷和碱性磷酸酶(ALP)含量,测量大鼠骨密度(BMD),ELISA法检测血清雌激素(E2)、骨钙素(BGP)、骨保护素(OPG)、核因子κB受体活化因子(RANK)和核因子κB受体活化因子配体(RANKL)水平。结果:与模型组比较,各给药组骨小梁显著变宽,数目增多,网状结构有部分恢复。各给药组骨小梁厚度、骨小梁面积和骨小梁面积百分数均大于模型组,骨小梁间距均小于模型组(P0.05)。各给药组血清中钙、磷、E2、OPG以及股骨BMD水平均显著高于模型组,ALP、BGP、RANK和RANKL水平均显著低于模型组(P0.01)。结论:自拟补肾活血颗粒对去卵巢大鼠骨质疏松症有显著的治疗作用。作用机制可能与上调OPG、抑制RANKL分泌有关。