骨灵丸对原发性骨质疏松症实验模型防治作用的研究

以补肝肾、填表髓的中骨灵丸进行防治原发性骨质疏松症（ＯＰ）的动物实验研究。通过制作原发性ＯＰ大鼠模型，并观测骨密度、骨生物力学、骨组织形态计量学指标，以观察骨灵丸疗效并探讨其主要作用机制。结果显示大鼠去势后出现高转换型ＯＰ，而骨灵丸能够有效对去势大鼠出现的骨丢失，维护鼠骨强度、弹性，保持骨生物力学性能，可使过高的破骨细胞（ＯＣ）活性降低，使骨吸收、骨形成二者之间偶联趋于平衡，从而有效地维持了鼠骨密     

补骨制剂Ⅱ对摘除卵巢大鼠骨质疏松的防治作用

目的研究补骨制剂Ⅱ经灌胃给药后对摘除卵巢大鼠骨质疏松模型的影响。方法雌性6月龄SD大鼠分为假去势组,模型组,阳性对照组,补骨制剂Ⅱ高、中、低剂量组(n=12),除假去势组进行假手术外,其余均手术彻底摘除卵巢法,术后进行模型筛选,9 d后假去势组、去势组均给予生理盐水,阳性对照组灌胃给予己烯雌酚0.02 mg/kg、鱼肝油450 U/kg、多种钙片0.5 g/kg,补骨制剂Ⅱ高、中、低剂量组分别灌胃给予补骨制剂Ⅱ稠浸膏(剂量以生药量计)12、6、3 g生药/kg,连续给药3个月。末次给药后,检测血清钙(Ca2+)、血清磷(P),超氧化物歧化酶(SOD)、丙二醛(MDA)、血清雌二醇(E2)含量,并测定骨密度、骨生物力学和骨组织形态。结果与去势组相比,低、中、高剂量补骨制剂Ⅱ组在鼠血清中各项检测指标均有显著差异(P0.05),增加腰椎骨密度,提高模型大鼠的股骨最大载荷和刚度,改善骨小梁数量和连续性。结论补骨制剂Ⅱ可明显改善去卵巢大鼠的骨生物力学性能,提高去势大鼠血清中雌激素水平,能防治去卵巢诱导的大鼠骨质疏松,是值得开发的一种中药复方制剂。     

金匮肾气丸联合葡萄糖酸钙对去势大鼠骨代谢的影响

目的观察金匮肾气丸联合葡萄糖酸钙对去卵巢大鼠骨代谢的影响,探究其防治骨质疏松(OP)的机制。方法将75只雌性大鼠随机分成假手术组,模型组,葡萄糖酸钙组,金匮肾气丸组,金匮肾气丸及葡萄糖酸钙联合用药组共5组,采用卵巢切除的方法制成OP动物模型,灌胃给药3个月后进行血清碱性磷酸酶(ALP)、骨钙素(OC)、白细胞介素-6(IL-6)等骨代谢指标的检测。结果金匮肾气丸联合葡萄糖酸钙治疗后,可明显降低去势大鼠升高的血清ALP、OC及IL-6水平,且效果优于单纯金匮肾气丸及葡萄糖酸钙。结论金匮肾气丸联合葡萄糖酸钙可显著改善骨代谢,抑制高骨转换过程,使骨形成与骨吸收趋于耦联,并使破骨细胞的分化增殖功能减弱,减少骨吸收,对OP具有较好的防治作用。     

糖尿病大鼠早期骨超微结构及生物力学改变的实验研究

目的观察糖尿病大鼠早期骨密度、骨超微结构及骨生物力学改变。方法清洁级健康成年雄性Wistar大鼠30只,随机分为A组(普通饲料对照组)、B组(高脂饲料 链脲佐菌素组)和C组(普通饲料 链脲佐菌素组)。饲养12w后对各组大鼠进行骨密度、光镜观察、扫描电镜观察、骨形态计量及骨生物力学等指标的检测。结果与A组相比,B组骨超微结构及骨生物力学无明显变化;C组骨超微结构及骨生物力学均明显下降(P<0.05)。结论不同的糖尿病大鼠模型早期骨超微结构及骨生物力学改变不完全一致,可能与高胰岛素血症、胰岛素抵抗有关。     

金匮肾气丸联合葡萄糖酸钙对去势大鼠骨微结构的影响

目的观察金匮肾气丸联合葡萄糖酸钙对去卵巢大鼠骨微结构的影响,探究其对骨质疏松(OP)的防治作用。方法将75只雌性大鼠随机分成假手术组,模型组,葡萄糖酸钙组,金匮肾气丸组,金匮肾气丸及葡萄糖酸钙联合用药组共5组,采用卵巢切除的方法制成OP动物模型,灌胃给药3个月后处死,取同侧股骨上段,进行骨形态计量学检测及扫描电镜观察。结果金匮肾气丸及葡萄糖酸钙均可增加骨小梁的百分面积,增加骨小梁数目,减轻骨吸收程度,改善骨胶原的排列及骨小梁立体网状结构,且联合组作用明显优于单纯金匮肾气丸组及葡萄糖酸钙组。结论金匮肾气丸联合葡萄糖酸钙能显著改善骨微结构,提高骨生物力学性能,增加骨强度,从而有效地防治OP。     

参茸补血丸对去卵巢大鼠骨质疏松防治作用的实验研究

目的研究以补肾养血为主的中药参茸补血丸防治骨质疏松的药效学基础，为临床应用提供实验依据。方法清洁级雌性SD大鼠，4．5月龄，体重260～300g，采用手术去除双侧卵巢方法。建立骨质疏松实验动物模型，随机分组。实验药物为参茸补血丸，对照药使用戊酸雌二醇（E2）、钙而奇D600，给药12W。测定骨密度、骨生物力学以及骨代谢相关指标。结果模型组下肢离体股骨、股骨头骨密度显著下降，股骨骨生物力学指标均显著下降，钙、镁代谢平衡异常。子宫指数显著下降，表明实验动物模型成立。与雌激素、钙而奇D作用相似，参茸补血丸具有明显增强股骨、股骨头骨密度，明显改善骨生物力学性能，明显降低抗酒钉酸酸性磷酸酶，明显增加骨钙含量；参茸补血丸＋钙而奇D600实验组可明显增加骨钙素含量等防治作用。结论参茸补血丸对防治骨质疏松症具有良好的效果。     

骨灵片对去卵巢骨质疏松大鼠腰椎骨形态计量学及生物力学的影响

目的观察补肾中药——骨灵片对去卵巢（OVX）骨质疏松（OP）大鼠腰椎的骨组织形态计量学以及生物力学影响,进一步探讨补肾中药治疗OP的机制。方法选择3月龄雌性SD大鼠36只,随机分为假手术组、OVX组、骨灵片低、中、高剂量组和雌激素组,每组各6只。试验4个月后采用骨形态计量学检测腰椎骨的动静态参数,生物力学凹入法检测腰椎的最大载荷和刚度。结果①与OVX组比较,骨灵片各剂量组和雌激素组的骨小梁分离度、骨形成率（BFR/BS、BFR/BV）、每mm破骨细胞数均有显著下降（P〈0.01）;骨灵片中剂量组BFR/TV和中高剂量组的骨矿化沉积率（MAR）减少有显著差异（P〈0.01）;骨灵片中高剂量组和雌激素组骨小梁面积百分数、厚度和数量显著升高且中剂量组的骨小梁厚度比雌激素组有显著增加（P〈0.05）;②生物力学上,与去卵巢组比较,雌激素组和骨灵片各剂量组的刚度以及骨灵片中高剂量组的最大载荷均有显著升高（P〈0.01）。骨灵片高剂量组在最大载荷上的提高较雌激素组有显著差异（P〈0.05）。结论补肾中药骨灵片具有促进骨形成和抑制骨吸收的双重作用,降低骨转换,使骨结构得到改善,并明显增加骨生物力学强度。     

上调Shh表达对去势骨质疏松大鼠干预效果及作用机制

目的 研究上调音猬因子(Shh)表达对去势骨质疏松模型大鼠的干预效果及作用机制。方法 选取清洁及健康的雌性昆明大鼠32只，随机选取8只分为正常组，剩余24只建立去势骨质疏松模型，分为模型组、空白组、上调组，各8只。比较各组Shh、碱性磷酸酶(ALP)、Ⅰ型胶原交联N-末端肽(NTX)、抗酒石酸酸性磷酸酶(TPACP)5b、骨密度、核因子KB受体活化因子配体(RANKL)、自噬相关蛋白(Beclin)1、微管相关蛋白1轻链(LC)3-Ⅱ、骨保护素(OPG)水平。结果 与模型组、空白组相比，上调组Shh表达、骨密度、OPG水平显著升高(P<0.05),ALP、NTX、TPACP5b、RANKL、Beclin1、LC3-Ⅱ水平显著降低(P<0.05),股骨最大扭矩、股骨最大载荷显著增大(P<0.05)。结论 上调Shh基因可通过调控RANKL、Beclin1、LC3-Ⅱ、OPG蛋白而降低ALP、NTX、TPACP5b水平，增强骨密度，进而降低骨代谢，改善去势骨质疏松大鼠的骨生物力学。     

仙珍骨宝对维甲酸致大鼠骨质疏松的影响

目的 探讨仙珍骨宝对维甲酸致大鼠骨质疏松的影响.方法 4月龄未交配的SPF级雌性SD大鼠24只,随机分成正常对照组、维甲酸组、仙珍骨宝组,持续给药28 d.大鼠处死后取股骨进行骨密度的测量,取第4腰椎进行生物力学参数测量,取胫骨上段测定骨形态计量学参数.结果 仙珍骨宝组腰椎生物力学指标均高于维甲酸模型组(P<0.05),但股骨骨密度和胫骨上段骨形态计量学参数与维甲酸模型组无明显差别(P>0.05).结论 仙珍骨宝可对抗维甲酸致大鼠腰椎生物力学性能的降低,但对骨密度和骨形态计量学参数无明显影响.     

老年性骨质疏松临床常用钙制剂的研究进展

<正>骨质疏松(OP)是一类以骨量低、骨组织微结构恶化导致骨脆弱性增强、易发生骨折风险为特征的疾病^[1]。该疾病分为原发性OP和继发性OP两大类。其中，原发性OP包括绝经后OP(Ⅰ型)、老年OP(Ⅱ型)和特发性OP(包括青少年型)。继发性OP是指任何影响骨代谢疾病和(或)药物及其他明确病因导致的骨质疏松。该病发病隐蔽性强，早期通常无明显症状，发生骨折后经X线检查或骨密度检查等后方被确诊。     

补肾中药组方对去卵巢大鼠骨生物力学的影响

目的 研究补肾中药组方（CKD）对去卵巢大鼠骨生物力学的影响.方法 60只雌性大鼠随机分为假手术组、卵巢切除（OVX）模型组、OVX＋CKD高剂量组、OVX＋CKD中剂量组、OVX＋CKD低剂量组和OVX＋雌二醇（E2）组,每组10只.3个月后,采用双能X线骨密度测定仪测定骨矿物质密度（BMD）并比较不同剂量CKD对OVX大鼠骨生物力学的影响.结果 模型组大鼠BMD有明显的下降（与假手术组比较,P＜0.05）;与模型组比较,小、高、中剂量组骨的最大载荷和挠度提高（P＜0.05）,高、中剂量组骨的弹性模量降低（与模型组比较,P＜0.05）,这种作用与尼尔雌醇作用相当（P＞0.05）;且补肾中药组方无明显的副作用.结论 补肾中药具有改善OVX大鼠骨生物力学的作用.     

保元汤加减对卡氏肺孢子虫肺炎模型大鼠的免疫调节作用初探

目的　观察中药保元汤加减煎剂对卡氏肺孢子虫肺炎模型大鼠免疫状态的调节作用 ,以探索中医药治疗卡氏肺孢子虫肺炎的新途径。　方法　在造模不同时间 ,以保元汤加减煎剂给卡氏肺孢子虫肺炎 (PCP)模型大鼠灌胃 ,2ml/次 ,1次 /d ,于造模后第 8周末 ,测定各组实验大鼠淋巴细胞转化率及T细胞亚群百分率。　结果　预防组大鼠淋巴细胞转化率明显高于PCP模型对照组 ,其值与正常对照组差异无显著性 ;预防组和治疗组大鼠的CD4+ 及CD4+ /CD8+ 值高于PCP模型对照组和治疗对照组 ,预防组CD4+ 及CD4+ /CD8+ 值与正常对照组差异无显著性。　结论　保元汤加减煎剂 ,可提高卡氏肺孢子虫肺炎模型大鼠的机体免疫功能 ,可作为防治卡氏肺孢虫子肺炎的药物。     

补肾中药复方对去卵巢骨质疏松大鼠皮质骨生物力学性能的改善作用及机制的实验研究

目的　探讨补肾中药复方对去卵巢骨质疏松模型大鼠皮质骨 (股骨 )生物力学性能的作用及其相关的机制。方法　将 50只 1 0月龄Wistar雌性大鼠随机分为 5组 ,每组 1 0只。正常对照组做假手术 ,其余 4组做卵巢切除术。术后正常饲养 90 d,第 91天开始给药 ,连续用药 90 d,处死 ,测定股骨的骨矿密度、几何尺寸和股骨的生物力学性能。结果　模型大鼠股骨的生物力学性能明显下降 ,骨强度降低 ;股骨干外径变细 ,股骨中段骨皮质面积减少 ,骨矿密度有所下降。补肾中药复方组 (密骨胶囊组和仙灵骨葆组 )大鼠股骨的生物力学性能明显提高 ,骨强度增加 ;股骨中段外径增粗 ,骨皮质面积增加 ,骨矿密度提高。结论　补肾中药复方通过提高去卵巢骨质疏松模型大鼠皮质骨 (股骨 )的宏观结构生物力学应答机能 ,明显改善其生物力学性能。     

仙灵骨葆改善骨质疏松大鼠股骨骨生物力学性能的作用及机制研究

目的探讨补肾中药仙灵骨葆对去卵巢骨质疏松模型大鼠皮质骨(股骨)生物力学性能的作用及其相关的机制。方法将40只10月龄wistar雌性大鼠随机分为仙灵骨葆组、倍美力组、正常组和模型组,每组10只。正常组做假手术,其余3组做卵巢切除术。术后正常饲养90 d。第91天开始,仙灵骨葆组、倍美力组分别给予临床等效剂量相应药物:仙灵骨葆55 mg/d(胶囊量),倍美力0.01 mg/d,正常组和模型组不给药。连续给药90 d后处死大鼠,测定股骨的几何尺寸、极惯性矩、抗扭截面模数、截面惯性矩、抗弯截面模数、骨矿密度和股骨的生物力学试验。结果模型大鼠股骨干外径变细,骨皮质面积减少,抗弯、抗扭截面模数变小,骨矿密度减损;股骨的生物力学性能明显下降,骨强度降低。用药组大鼠股骨干外径增粗,骨皮质面积增加,抗弯、抗扭截面模数增大,骨矿密度提高。股骨的生物力学性能明显改善,骨强度增加。结论仙灵骨葆能够提高股骨宏观结构的生物力学应答调节功能,使股骨干外径增粗,皮质骨面积增加,骨丢失减少使股骨结构的抗弯、抗扭截面模数增大,使骨的力学结构优化,骨强度提高。     

Nuclear factor‐kappa B as a promising target for selenium chemoprevention in rat hepatocarcinogenesis

Background and Aims: Selenium's molecular mechanism for cancer chemoprevention remains unknown. We aimed to study the gene expression of nuclear factor‐κB (NF‐κB), tumor growth factor‐α (TGF‐α) and cyclin D1 and the effects of sodium selenite using preventive and therapeutic approaches in chemically‐induced hepatocarcinogenesis in rats. Methods: Rats were divided randomly into six groups: negative control, positive control (diethyl nitrosamine [DEN] + 2‐acetylaminofluorene [2‐AAF]), preventive group, preventive control (respective control for preventive group), therapeutic group and therapeutic control (respective control for therapeutic group). The relative gene expression of NF‐κB, TGF‐α and cyclin D1 in liver tissues were measured using real‐time polymerase chain reaction. Results: The findings showed that the gene expression of NF‐κB in the preventive group and its respective control was significantly lower (P < 0.05) when compared with both the negative and positive controls. However, the expression of NF‐κB in the positive controls and therapeutic group was significantly higher (P < 0.05) when compared with the negative controls. The expression of TGF‐α and cyclin D1 was insignificant in all groups. Conclusion: The inhibition of the NF‐κB pathway in the initiation phase of hepatocarcinogenesis could be a promising target for selenium chemoprevention. However, further studies are required.     

New promising avenue for the simvastatin combination with residronate,strontium ranelate and raloxifene in experimentally-induced osteoporosis

Aim of the workThis is the first experimental study to assess the possible synergistic effects of simvastatin combination with residronate, strontium ranelate and raloxifene on glucocorticoid induced osteoporosis (GIO) in female albino rats.Materials and methods48 mature healthy female albino rats were randomly allocated into 6 main groups (8 rats /group) and received all drugs daily orally for 6 weeks. (G1) negative control group; (G2) osteoporotic group that received prednisolone at 15 mg/kg/day; (G3) prednisolone + 10 mg/kg/day simvastatin; (G4) received prednisolone + simvastatin + residronate 1 mg/kg/day; (G5) prednisolone + simvastatin + strontium ranelate 600 mg/kg/day; (G6) prednisolone + simvastatin + raloxifene at 1.25 mg/kg/day. After 6 weeks, mean arterial blood pressure (MAP), ejection fraction and left ventricular diameter were assessed. Bone histomorphometry, serum level of bone specific alkaline phosphatase (BsALP), osteocalcin (OCN), calcium, phosphorus, AST and ALT and bone mineral assessment by DEXA.ResultsSimvastatin combined regimens-treated groups exerted significant marked amelioration of osteoporotic changes by achieving the highest histopathological score, bone mineral density by DEXA scan, increase in serum Ca, OCN and decrease in BsALP especially in simvastatin combined groups (G4 and G5) whereas, simvastatin combined groups (G4 and G6) exerted more significant improvement in cardiovascular adverse events regarding the elevated MAP, cardiac hypertrophy and dysfunction as compared to osteoporotic non-treated group2 (p < 0.0001).ConclusionSimvastatin combined regimens have promising synergistic effects on bone microarchitecture with cardiovascular protective effects which might be considered by clinicians as valid preventive and therapeutic strategy in patients with osteoporosis with or highly susceptible to cardiovascular disease.     

Whole Leea macrophylla ethanolic extract normalizes kidney deposits and recovers renal impairments in an ethylene glycol-induced urolithiasis model of rats

ObjectiveTo investigate the antilithiatic effect of the whole Leea macrophylla (L. macrophylla) Roxb (Leeaceae) ethanol extract in ethylene glycol-induced urolithiasis model of rats.MethodsForty two seven weeks old male wistar albino rats were randomly divided into two major groups namely: preventive (n=18) and therapeutic (n=24). Preventive group was further subdivided into 3 groups of 6 rats namely: preventive control (PC), preventive lithiatic control (PLC) and preventive lithiatic L. macrophylla (PLLM). Similarly, therapeutic group was also subdivided into 4 groups of 6 rats namely: therapeutic control (TC), therapeutic lithiatic control (TLC), therapeutic lithitatic L. macrophylla (TLLM) and therapeutic lithiatic cystone (TLCYS). The lithiasis was induced by 0.75% (v/v) ethylene glycol in the drinking water of all groups except the PC and TC groups. The urinary ionic parameters such as calcium, inorganic phosphate, oxalate, magnesium &; creatinine and renal morphology were altered by ethylene glycol, which were partially recovered by 14 d preventive and almost fully recovered by 28 d therapeutic intervention trials with L. macrophylla extract (500 mg/kg BW daily).ResultsSignificant difference on recovery was observed between preventive and therapeutic interventional trials. Anti-urolithiatic effect of cystone was significantly (P<0.001) higher than extracts. L. macrophylla extract was found nontoxic in the acute toxicity test.ConclusionThe results of this study demonstrated very promising anti-urolithiatic effect of L. macrophylla extract with preventive and therapeutic treatments in this experimental condition.     

Osteoporosis,densidad mineral ósea y complejo CKD-MBD (I): consideraciones diagnósticas

Osteoporosis (OP) and chronic kidney disease (CKD) independently influence bone and cardiovascular health. A considerable number of patients with CKD, especially those with stages 3a to 5D, have a significantly reduced bone mineral density leading to a high risk of fracture and a significant increase in associated morbidity and mortality. Independently of classic OP related to age and/or gender, the mechanical properties of bone are also affected by inherent risk factors for CKD (“uraemic OP”). In the first part of this review, we will analyse the general concepts regarding bone mineral density, OP and fractures, which have been largely undervalued until now by nephrologists due to the lack of evidence and diagnostic difficulties in the context of CKD. It has now been proven that a reduced bone mineral density is highly predictive of fracture risk in CKD patients, although it does not allow a distinction to be made between the causes which generate it (hyperparathyroidism, adynamic bone disease and/or senile osteoporosis, etc.). Therefore, in the second part, we will analyse the therapeutic indications in different CKD stages. In any case, the individual assessment of factors which represent a higher or lower risk of fracture, the quantification of this risk (i.e. using tools such as FRAX^®) and the potential indications for densitometry in patients with CKD could represent an important first step pending new clinical guidelines based on randomised studies which do not exclude CKD patients, all the while avoiding therapeutic nihilism in an area of growing importance.     

何首乌饮对衰老大鼠下颌下腺NGF mRNA、EGF mRNA表达的影响

目的探讨何首乌饮对衰老大鼠下颌下腺神经生长因子(NGF)、表皮生长因子(EGF)基因表达的影响。方法选用8周龄SD雌性大鼠90只,用D-半乳糖制造衰老大鼠模型,何首乌饮的干预作用分治疗和预防两部分,用原位杂交法检测各组大鼠下颌下腺NGF mRNA、EGFmRNA表达的情况。结果预防性实验部分的组间NGF mRNA、EGF mRNA表达比较差异有统计学意义(P<0.01),其中以正常组最高,模型组最低,各预防组处于中间水平,其中预防中剂量组最高。治疗性实验部分的组间NGF mRNA、EGF mRNA表达比较差异有统计学意义(P<0.01),其中以阴性对照组最高,自然恢复组最低,各治疗组处于中间水平,其中中剂量组最高。结论何首乌饮可在基因转录水平提高NGF、EGF的表达。     

Effects of aspirin on fracture healing in OPF rats

Objective:To study the effect of aspirin on healing process of osteoporotic fracture(OPF)in rats.Methods:A total of 50 female Wistar rata aged 3 months were randomly divided into observation group and control group,castration method was adopted to establish the osteoporosis(OP)model.After artificial preparing fractures on the midpoint of left femur,fixing gram needle intramedullary.OPF modeling was complete.Aspirin lavage of 33 mg once a day was adoptde in observation group after modeling,same amount of normal saline was used in the control as placebo.From eash group,selected 5 rats at the 2nd.4th,8th and 12th week after modeling to measure the bone mineral density(BMD)and histogical examination of the fracture callus,radiology observation was conducted at the 8th and 12th week.Left femur biomechanical measurement was taken at the 12th week.Results:BMD values of observation group at each time point were significantly higher than that of the control group after modeling(P0.05);Histological observation showed that at the 8th week,the endochondral ossification process of observation group was faster than that of observation group,with fuzzy fracture line in observation group and clear fracture line in observtion group;at the 12th week,fracture line disappeared in observation group,fracture line of the control group was fuzzy at the same time;three-point bending load of the left femur in observation group rats was significantly higher than that of control group after12 weeka(P0.05).Conclusions:Asporin can accelerate the healing of new callus in OPF rats,increase bone density and biomechanics strength,and promote fracture of osteporotic rats.