辅酶Q10对环磷酰胺大鼠股骨的显微结构和生物力学的影响

目的应用骨生物力学和micro-CT技术,探讨Co Q10对环磷酰胺大鼠股骨的显微结构和生物力学的影响,并与阳性药物阿仑磷酸钠对比。方法 32只SPF级♂SD大鼠,随机分为正常对照组(CON)、环磷酰胺组(CTX)、阿仑膦酸钠组(ALD)、辅酶Q10组(Co Q10),连续给药15 d。实验结束后,取右侧股骨进行生物力学检测,然后进行Micro-CT扫描及三维重建。结果与CON组比较,CTX组大鼠股骨的骨微观参数:骨体积分数、骨小梁数量、骨小梁厚度和骨密度明显减少,骨小梁分离度和结构模型指数明显增高;而股骨的骨生物力学参数:最大强度、断裂强度、断裂应变及韧性系数明显减少,刚性系数明显增加。与CTX组相比,ALD组大鼠股骨的骨微观参数均得到了良好地修复,但骨生物力学参数中仅断裂应变、韧性系数和刚性系数三个参数得到了明显修复。而Co Q10组大鼠股骨的微观参数仅骨体积分数和骨小梁厚度两个参数得到明显修复,但骨生物力学参数除断裂应变外均得到了明显修复。结论 Co Q10(30 mg·kg-1·d-1)修复CTX大鼠股骨微观结构的能力有限,但修复骨质量、降低股骨骨折风险的能力优于ALD,提示Co Q10的抗骨质疏松作用具有良好的研究前景。     

多组分缩合反应合成肽核酸类化合物.Ⅰ.肽核酸单体的合成

目的 对新型反义核酸类化合物肽核酸（PNA）进行结构改造。探索并利用多组分缩合反应（Ugi反应）进行PNA类似物单体的合成。方法 改变了一般合成PNA的思路，采用Ugi反应进行PNA的合成。结果 设计并合成了Ugi反应中的关键组分：异腈，PNA单体。结论 所得产物经MS，IR，^1H-NMR及元素分析确证与目标化合物相符。该反应具有步骤简单，基团变换灵活的优点。     

黄柏小檗碱对去卵巢大鼠骨质疏松症的作用

目的：研究黄柏小檗碱对去卵巢大鼠骨质疏松症的作用.方法：去卵巢以建立大鼠骨质疏松症模型,将大鼠随机分为假手术组、去卵巢组,尼尔雌醇组及低（10 mg/kg）、中（30 mg/kg）、高（90 mg/kg）剂量黄柏小檗碱组进行实验,每组10只.12周后,以比色法测定其血清钙、磷的浓度和碱性磷酸酶的活性,竞争放射免疫法测定血清中骨钙素、降钙素、甲状旁腺素及雌二醇的浓度;双能X射线骨密度仪测定大鼠股骨干骺端的骨密度.结果：黄柏小檗碱能够增加去卵巢大鼠子宫重量、股骨干骺端的骨密度和血清无机磷含量;降低碱性磷酸酶活性和甲状旁腺素浓度,增加血清雌二醇、骨钙素、降钙素浓度.结论：黄柏小檗碱对去卵巢大鼠骨质疏松症具有防治作用,其机制可能是抑制骨吸收、促进骨形成,促进雌二醇和降钙素合成.     

泼尼松对Ⅱ型胶原诱导性关节炎大鼠股骨微结构及生物力学的影响

目的应用骨生物力学和micro-CT技术,探讨泼尼松对Ⅱ型胶原诱导性关节炎(CIA)大鼠股骨微结构及生物力学的影响。方法 40只8周龄Lewis♂大鼠,随机分为正常对照(CON)组6只、其余34只用来建立CIA模型。免疫3周后筛选出CIA大鼠随机分成CIA组、CIA加泼尼松4.5mg·kg-1·d-1组和CIA加泼尼松9 mg·kg-1·d-1组。CON和CIA组给予溶剂对照溶液,其它2组给予泼尼松4.5、9 mg·kg-1·d-1。连续给药90 d后处死,取左股骨进行生物力学测定,然后进行micro-CT扫描及三维重建。结果与CON组比较,CIA组骨小梁厚度、骨小梁数量、骨体积分数、骨密度明显减小,而骨小梁分离度、结构模型指数明显增加,骨生物力学参数(弹性载荷、最大载荷、断裂载荷、刚度)均明显减小。与CIA组比较,泼尼松2个剂量组骨体积分数与骨小梁数量均增加,骨小梁分离度均减小,而骨生物力学参数均无明显变化。结论泼尼松治疗CIA大鼠3个月后,对股骨松质骨微结构破坏有所改善,但对股骨生物力学性能和骨密度没有明显改变。     

去睾丸大鼠骨质疏松模型的实验研究

目的：建立去睾大鼠骨质疏松模型，研究大鼠去睾后股骨颈骨密度及骨微结构的变化。方法：选用19只12－16周龄的Wistar雄性大鼠，随机分成去睾组和假去睾组，同条件下饲养18周。处死前用Hologic QDR-2000 DEXA测量大鼠腰椎、股骨颈、股骨粗隆部、股骨近端的骨密度。处死前第14、13天和第3、2天行骨荧光标记，大鼠处死后取左侧股骨近端行塑料包埋的骨组织切片及组织形态计量学分析。结果：去睾大鼠18周后腰椎、股骨颈、股骨粗隆部、股骨近端的骨密度均下降，与假去睾组有显的统计学差异（P＜0．01）。骨组织形态计量学静态参数表现为去睾组的骨小梁面积百分率（％Tb.Ar)减少46。4％（P＜0．01），骨小梁数目（Tb.N)减少43．8％（P＜0．01），骨小梁分离度（Tb.Sp)增加144．6％（P＜0．01）。动态参数表现为去睾组的骨荧光标记周长百分率（％L.Pm)增加124％（P＜0．01），骨形成率BFR／BS，BFR／BV和BFR／TV分别增加437．6％（P＜0．01），239．9％（P＜0．01），240．3％（P＜0．01）。代表骨吸收的参数骨小梁面积破骨细胞数（Oc.No)和骨小梁周长破骨细胞数（Oc.No/Pm)分别增加131．9％（P＜0．01），115．5％（P＜0．01）。结论：大鼠去睾18周后腰椎、股骨近端均出现骨丢失，表现为高转换型骨代谢，骨吸收大于骨形成而形成了骨质疏松模型。大鼠股骨颈是研究骨质疏松症动物模型的组织形态计量学的理想部位。     

取代环戊酮曼尼希碱的合成及其抗炎活性

目的 对环戊酮曼尼希碱类化合物JC9118进行结构改造，设计合成其类似物并初步评价抗炎活性。方法 以N－环戊烯基吗啉，对异丁基苯甲醛，对异丁基苯乙酮及多种胺类为原料经Stork反应，Mannich反应和胺交换反应合成目标化合物，并以二甲苯致小鼠耳肿胀模型测试目标化合物的抗炎活性。结果 合成9个新化合物，经IR，^1H-NMR和MS确证其结构；其中5个化合物具有显著的抗炎活性。结论 JC9118的芳胺曼尼希碱类似物无抗炎活性；羰基α位的取代亚苄基对保持化合物的抗炎活性起重要作用。     

记忆增强肽ZNC（C）PR类似物的结构—活性关系

ＺＮＣ（Ｃ）ＰＲ是大鼠脑中具有促进学习记忆作用的神经肽，本文按前文２Ｄ－ＮＭＲ测定结构和活性比较的结果以及分子动力学的关系式计算了４５个ＺＮＣ（Ｃ）ＰＲ类似物的能量和可能的结构趋势向，从理论上探讨了各残基对稳定结构的贡献，并据此设计和合成了５个新的类似物加以验证，结果与预测，即一定紧密度的分子结构是表现活性所必需的。     

1-烷基-6-氟-1,4-二氢-7-(4-酰基-1-哌嗪基)-4-氧代喹啉-3-羧酸类似物的合成及其抗菌活性

目的 设计合成具有广谱抗菌活性的含氟喹诺酮类化合物。方法 利用吡酮酸7位哌嗪基4位氮上存在的活性氢为反应修饰基点，与磺酰氯，酰氯，氯甲酸酯进行Schotten-Baumann酰基化反应设计合成一系列含有磺酰基、酰基和烷氧羰基类氟喹诺酮类似物。结果 合成了20个含有磺酰基、酰基和氧羰基的氟喹诺酮类似物，利用元素分析、核磁共振进行了结构确认。结论 合成了16个未见报道的新化合物，初步体外活性测试结果表明，其中的4个化合物有较高的生物活性。     

腺苷的结构改造与细胞毒活性研究

目的： 为寻找新型抗肿瘤化合物和探讨糖环羟基对8-Cl-腺苷的抗肿瘤活性的影响,合成了腺苷的维甲类似物和8-Cl-腺苷衍生物。方法： 对腺苷的8位和8-Cl-腺苷的糖环羟基进行了结构改造,以酰胺键和酯键在腺苷的8位连接了具共轭基团的肉桂酰基和苯甲酰基,得到腺苷的维甲类似物;对8-Cl-腺苷的5′-羟基进行了甲磺酰化,硝基化以及氯代反应,得到了它的衍生物。结果： 合成了(6～12),(16),(18～20)等11个新化合物。结论： 这些新化合物以HL-60,BIU,KB细胞株的细胞毒为指标进行生物活性筛选,结果表明,8-位取代基和5′-羟基是影响腺苷类化合物细胞毒活性的重要药效基团。     

骨立拮抗维甲酸所致大鼠骨质疏松的实验研究

目的　观察骨立对维甲酸所致骨质疏松大鼠的股骨骨密度、骨矿含量的影响。方法　采用ig维甲酸造成大鼠骨质疏松模型 ,使用骨立高、中、低 3种剂量分别进行治疗 ,观察其结果并与空白对照组和阳性对照药物组进行比较。结果　骨立 3个剂量治疗的骨质疏松大鼠的股骨骨密度和骨钙、骨磷含量均明显高于骨质疏松模型组大鼠 (P <0 .0 1或 0 .0 5 ) ,骨立高、中剂量组大鼠的尿钙排泄量明显低于骨质疏松模型组大鼠 (P <0 .0 1) ,其中以高剂量组疗效最佳。结论　骨立可明显提高骨质疏松大鼠的骨密度并升高其骨钙、骨磷的含量 ,降低尿钙排泄量 ,从而拮抗维甲酸所致的大鼠骨质疏松症。     

骨质疏松症临床实践指南评价及药物综合价值研究

目的：利用指南质量评价工具第二版（AGREEⅡ）评价国内外骨质疏松临床实践指南的质量,并为骨质疏松症人群用药选择提供参考。方法：计算机检索中英文文献数据库及国内外常用指南网站,根据纳入排除标准筛选骨质疏松症指南。采用AGREE Ⅱ工具评价指南质量,同时进行药物临床价值评价。结果：共纳入40篇指南,各领域得分依次为范围和目的97.18%、参与人员46.34%、严谨性46.61%、清晰性93.39%、应用性40.90%、独立性56.74%。其中A级推荐指南3篇,B级和C级推荐指南分别为33篇和4篇。骨质疏松症药物临床价值由高到低依次为：双磷酸盐、甲状旁腺激素类似物、选择性雌激素受体调节剂、RANKL抑制剂、钙和维生素D、降钙素、雌激素、锶盐、维生素K₂、活性维生素D及其类似物、氟化盐、选择性抑制甲状旁腺激素（PTH）分泌的拟钙剂等。绝经后、男性和糖皮质激素致骨质疏松三类亚人群中双膦酸盐仍为较高治疗价值药物。结论：国内外现有的骨质疏松临床实践指南总体质量一般,各国骨质疏松指南的制订需进一步规范化,各类人群的推荐用药也需进一步明确以方便使用。     

预防和治疗骨质疏松症的有效药物依普黄酮

目的：为新药依普黄酮上市第指导临床合理用药提供参考。方法：从依普黄酮的作用机理，临床研究及与激素替代疗法（HRT）、降钙素（CT）临床对比等阐明其特点。结果：本品属植物性促进骨形成药物，能直接作用于骨，具雌激素样的抗骨质疏松特性，但无雌激素对生殖系统的影响。与降钙素有相似的疗效但便于使用和治疗，结论：依普黄酮是一种预防和治疗骨质疏松症的有效安全的药物。     

维甲酸致小鼠骨质疏松模型的量效关系及骨药理作用探讨

目的　观察不同剂量维甲酸致小鼠骨质疏松的量效关系 ,探讨维甲酸性骨质疏松的的骨代谢作用特点及骨药理学作用机制。方法　用 3种剂量维甲酸造成小鼠骨丢失为主的骨质疏松模型 ,监测体重 ,2wk后处死小鼠 ,取肝、脾、胸腺称重 ,并取股骨进行骨干重、骨钙、磷、镁、锌、锰、硫及骨羟脯氨酸 (B HOP)的测定和比较。结果　不同剂量维甲酸均分别致小鼠骨干重减少 ,骨横短径减少 ,骨基质的主要成分骨羟脯氨酸 (HOP)减少 ,骨矿物质也有不同程度的减少 ;骨HOP及骨钙的减少与骨干重的比值密切相关 ,但骨磷、镁、锌的减少呈非等比例性减少 ,尤以骨锌明显。结论　维甲酸 3种剂量均可引起小鼠以骨量丢失为主的骨质疏松 ,并呈量效关系 ,其特征是骨钙及骨羟脯氨酸等比例性丢失 ,早期以骨磷、镁、锌的明显丢失为主 ,骨锌在维甲酸致骨质疏松模型中可能发挥重要作用     

益肾补骨片抗骨质疏松的药效学研究

目的:探讨益肾补骨片抗骨质疏松的药效学.方法:采用给动物灌服一定剂量的维甲酸,造成动物股骨骨质疏松的病理模型,给予益肾补骨片治疗并观察其疗效.结果:该制剂可显著改善骨骼的病理性改变,且有良好的改善微循环作用,可在一定程度上增加股动脉血流量.结论:益肾补骨片具有抗骨质疏松、改善微循环、增加下肢血液供应的作用.     

Curcumin alleviates glucocorticoid‐induced osteoporosis by protecting osteoblasts from apoptosis in vivo and in vitro

Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti‐inflammation and anti‐cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid‐induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)‐induced osteoporosis in vivo and Dex‐induced osteoblast apoptosis in vivo and in vitro. The GIO rat model was induced by subcutaneous injection of Dex for 60 days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X‐ray absorptiometry. Subsequently, curcumin administration (100 mg/kg) for 60 days obviously increased BMD and bone‐alkaline phosphatase, decreased carboxy‐terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex‐induced osteoporosis. Mechanically, curcumin remarkably reversed Dex‐induced femoral osteoblast apoptosis in vivo. In cultured primary osteoblasts, pretreatment with curcumin concentration‐dependently decreased the number of Dex‐induced apoptotic osteoblasts by down‐regulating the ratio of Bax/Bcl‐2 as well as the levels of cleaved caspase‐3 and cleaved poly ADP‐ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex‐induced osteoblasts by up‐regulating the expression level of p‐ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.     

降钙素及甲状旁腺激素在骨质疏松中的诊断价值探讨

目的：探讨降钙素和甲状旁腺激素在骨质疏松中的诊断价值。方法：选择96例骨质疏松患者为观察组,另选85例非骨质疏松患者为对照组,检测血液中的降钙素和甲状旁腺激素浓度,并与前臂远端、第四腰椎、股骨大转子的骨密度水平比较分析,探讨降钙素和甲状旁腺激素在骨质疏松中的诊断价值。结果：观察组血液中降钙素和甲状旁腺激素浓度分别为（13.71±1.49）pmol/mL、（22.63±6.172）pg/mL,前臂远端骨、第四腰椎、股骨大转子的骨密度水平分别为（0.53±0.65）g/cm2、（0.76±0.19）g/cm2、（0.73±0.18）g/cm2,与对照组比较,降钙素浓度水平低于对照组（P<0.05）,甲状旁腺激素浓度水平则明显高于对照组（P<0.01）。结论：老年骨质疏松症患者血液中的降钙素和甲状旁腺激素浓度变化比较明显,在骨质疏松的诊断中有较大的意义。     

淫羊藿总黄酮抗骨质疏松作用研究

目的:探讨淫羊藿总黄酮的抗骨质疏松作用.方法:灌胃给予维甲酸14 d,造成大鼠骨质疏松症.以淫羊藿总黄酮连续给药28 d,检测血清钙、血清磷、碱性磷酸酶水平的变化,并取股骨进行骨钙含量测定及股骨病理组织学检查.结果:各剂量的淫羊藿总黄酮对血清钙、血清磷、碱性磷酸酶正常生理水平均无显著影响,但均可增加股骨骨钙含量、骨皮质厚度及骨小梁数量.结论:淫羊藿总黄酮对骨质疏松症具有明显的预防和治疗作用.     

Maxcal-C (a polyherbal formulation) prevents ovariectomy-induced osteoporosis in rats

Objectives:

The aim of the present study was to investigate the anti-osteoporotic activity of Maxcal-C in ovariectomy (OVX)-induced osteoporosis in rats.

Materials and Methods:

Sham-operated control rats were designated as Group I; Group II animals served as OVX control; Group III OVX control rats treated with Calcium Sandoz (50 mg/kg, p.o.); Group IV and V OVX control rats treated with Maxcal-C (250 and 500 mg/kg, p.o.), respectively. All the aforementioned treatments were given for four weeks after the development of osteoporosis. At the end of the treatment, serum biochemical parameters such as serum calcium and alkaline phosphate were measured. After sacrificing the animals, femoral bone parameters with histology, body weight, and bone breaking strength of 5^th lumbar vertebra were measured.

Results:

The treatment with Maxcal-C showed a significant improvement in serum biochemical, femoral bone parameters, and bone breaking strength of 5^th lumbar vertebra with histopathological changes.

Conclusion:

The finding of the present study indicates that Maxcal-C showed a potential anti-osteoporotic activity. These results support the traditional use of Maxcal-C in the treatment of osteoporosis.KEY WORDS: Bone breaking strength, femoral bone parameters, Maxcal-C, ovariectomy rats, serum calcium     

Chronopharmacology of oxacalcitriol in rat model of osteoporosis

We have previously reported the merits of chronopharmacological effect of 1-alpha(OH) vitamin D3 in aged stroke-prone spontaneously hypertensive rat (SHRSP), a model of osteoporosis [Eur. J. Pharmacol. 428 (2001) 283.]. In this study, the chronopharmacological effect of 22-oxacalcitriol, a newly developed active vitamin D3 analogue with less calcemic activity, was evaluated by a single and repeated dosing of the drug in aged SHRSP. Animals (7 months old) were kept in rooms with a 12-h light/dark cycle. Single (12.5 microg/kg, i.v.) and repeated (5 microg/kg, i.v. three times a week for 12 weeks) dosing of 22-oxacalcitriol or vehicle was given at either 2 h after lights on (2HALO) or 14 h after lights on (14HALO). The severity of adverse reactions such as the changes of body weight, hypercalcemia and hyperphosphatemia, was significantly mild when the drug was given at 14HALO. Especially, the increase of serum Ca concentration was not detected at 14HALO trial. Serum concentrations of total (protein-bound and unbound) 22-oxacalcitriol and albumin (a major binding protein of the drug) of the 2HALO and 14HALO trials did not significantly differ. The decrease of parathyroid hormone (PTH) concentration was greater in the 14HALO trial while the increase in urinary ratio of Ca to creatinine was greater in the 2HALO trial. The increase in bone density of both femurs at the end of the study was greater in the 14HALO trial. The suppression of urinary excretion of deoxypyridinoline, an index of bone resorption capacity of osteoclast, was greater in the 14HALO trial, which indicates that the efficacy of 22-oxacalcitriol for suppressing bone resorption might vary with the dosing time. This is the first study to show the dosing-time-dependent changes in the efficacy and toxicity of 22-oxacalcitriol in the animal model of osteoporosis. Chronopharmacological differences seem to be more prominent than those of other vitamin D analogues. To use 22-oxacalcitriol at an adequate timing might provide better efficacy and safety than other vitamin D3 analogues for the treatment of osteoporosis.     

Increased serum GDF11 concentration is associated with a high prevalence of osteoporosis in elderly native Chinese women

Osteoporosis is an age‐related disease. Many studies have confirmed the anti‐aging effect of growth differentiation factor 11 (GDF11), but the action of GDF11 on bone metabolism remains unclear. In this study, we aimed to investigate the relationship between serum GDF11 levels and the prevalence of osteoporosis. Our data indicate negative correlations between serum GDF11 levels and BMD at the lumbar spine and femoral neck. The serum GDF11 levels were grouped into quartile intervals, and the prevalence and risk of osteoporosis were found be markedly greater with increased GDF11 levels. This study demonstrated that GDF11 was negatively correlated with BMD in elderly Chinese women. Furthermore, osteoporotic risk was significantly increased with increases in GDF11 levels.