葛根素预防雌激素缺乏性骨质疏松的机制探讨

目的观察葛根素对去卵巢大鼠股骨骨密度、颌骨骨密度和血清中肿瘤坏死因子（TNF-α）、C反应蛋白（CRP）及雌二醇（E2）水平的影响。方法 3月龄雌性SD大鼠随机分为假手术组（sham group）、单纯去势组（OVX group）、去势＋雌二醇治疗组（OVX-estrogen group）和去势＋葛根素治疗组（OVX-puerarin group）。给药3个月后测量各组大鼠股骨和颌骨骨密度,血清中TNF-α和CRP及雌二醇（E2）水平。结果 OVX-puerarin组较sham组体重明显增加（P〈0.01）;较OVX-estrogen组的TNF-α（P〈0.01）、CRP（P〈0.05）及E2（P〈0.01）水平显著下降;其下颌骨和股骨远端骨密度与OVX组、sham组之间无显著性差异,但其股骨近端骨密度较OVX-estrogen组明显增加（P〈0.05）。结论葛根素作为抗炎因子,能够显著降低TNF-α和CRP的水平,但并不会提高雌激素的水平;葛根素对卵巢切除所致的骨质疏松症有一定的治疗作用,但会明显提高机体体重。     

羊骨酶解发酵液钙鳌合物对骨质疏松大鼠骨密度和骨代谢生化指标的影响

目的探讨羊骨酶解发酵液钙螯合物（SBEF-Ca）对雌激素缺乏造成的骨质疏松的防治作用。方法 40只3.5月龄的Sprague-Dawley大鼠,按体重随机分为正常组（假手术＋蒸馏水）、模型对照组（去卵巢＋蒸馏水）和高、中、低3个剂量组（去卵巢＋SBEF-Ca）。术后12 d,持续灌胃11周后,测定股骨密度、长度以及血清中反映骨代谢的主要生化指标。结果模型对照组大鼠股骨密度和长度显著减小,各剂量组均可扭转这种减小趋势并使股骨密度和长度维持在正常组水平,其中高剂量组的股骨密度显著大于中、低剂量组;各剂量组的股骨长度差异不显著;所有大鼠的血Ca、血P水平差异无显著性;模型对照组的血清碱性磷酸酶（ALP）、骨钙素（BGP）水平明显升高,而各剂量组的ALP、BGP水平与正常组差异不显著,且高剂量组ALP水平显著低于中、低剂量组,中、高剂量组的BGP水平（P〉0.05）显著低于低剂量组。结论低、中、高剂量的SBEF-Ca对绝经后骨质疏松症有预防作用。     

葛根异黄酮对去卵巢大鼠骨质疏松症的影响

通过对3月龄Wister大鼠,手术切除双侧卵巢后7天,每天灌胃TIP40mg/kg和10mg/kg,并设去卵巢组(OVX)、假手术组(Sham)和尼尔雌醇阳性对照组(OVX-E2),在给药3个月时,测定大鼠股骨骨矿密度(BMD)、骨钙及血清钙水平等,研究葛根异黄酮(TIP)对由雌激素缺乏引起的骨质疏松症的防治作用。结果TIP40mg/kg的BMD比去卵巢组显著提高了18.1%;使胫骨和血清钙含量显著增加;使去卵巢大鼠的脾脏重量系数和胸腺重量系数明显恢复;并可明显控制大鼠的体重。葛根异黄酮可能具有雌激素样活性,并有改善骨质疏松症的生物学活性。     

黄芪桂枝五物汤对AA大鼠血清IL-1β、TNF-α的影响

目的:探讨佐剂性关节炎大鼠血清中IL-1β、TNF-α含量的变化和黄芪桂枝五物汤对其变化的影响,以求阐明该黄芪桂枝五物汤治疗类风湿性关节炎的作用机制。方法:选用健康SPF级SD雌性大鼠60只随机分为六组:空白对照组,模型组,甲氨喋呤(MTX)组,黄芪桂枝五物汤高剂量组,黄芪桂枝五物汤中剂量组和黄芪桂枝五物汤低剂量组。大鼠先进行一周的适应性饲养后用完全弗氏佐剂诱导制作大鼠佐剂性关节炎模型,并用黄芪桂枝五物汤进行干预。采用放射免疫法测定大鼠血清中IL-1β、TNF-α的含量。结果:与空白时照组相比,模型组大鼠血清中细胞因子IL-1β、TNF-α的水平明显升高(P<0.01);与模型组相比,经黄芪桂枝五物汤高、中剂量组、MTX组治疗干预后,大鼠血清中IL-1β、TNF-α的水平明显下降,且呈现一定的量效关系。结论:黄芪桂枝五物汤有抑制佐剂性关节炎大鼠血清中细胞因子IL-1β、TNF-α升高的作用。     

毛菊苣醇提物对高脂血症性脂肪肝大鼠作用机制初探

目的:目前,国内外研究集中在毛菊苣降糖降脂方面的作用,并已有相关药物上市,但实验表明毛菊苣在保肝降脂作用方面也具有很好的效果,本文旨在探讨毛菊苣醇提物治疗高脂血症性脂肪肝的作用机制。方法:采用高脂饮食喂饲大鼠复制高脂血症性脂肪肝大鼠模型,实验分组为模型组、毛菊苣醇提物治疗高剂量组和低剂量组、苯扎贝特对照组和正常对照组;以高、低剂量毛菊苣醇提物进行干预,然后测定各组大鼠血清及肝组织中乳酸脱氢酶(LDH)、低密度脂蛋白(LDL)、甘油三酯(TG)、胆固醇(TC)、丙二醛(MDA)等指标的含量。结果:模型组大鼠血清及肝组织中LDH、TG、TC、LDL、MDA等活性均较正常组明显升高(P0.05),说明高脂饲料造模成功;与模型组比较,测得各治疗组大鼠血清、肝组织中相应指标均明显降低(P0.05;或P0.1);毛菊苣醇提物高剂量组与阳性对照组相比无显著差异。结论:实验结果表明:通过高脂饮食饲喂SD大鼠建立高脂血症动物模型的实验是成功的;同时,毛菊苣醇提物能够使脂肪肝大鼠的体重降低,降低肝脏脂肪性病变,降低脂肪肝大鼠血清ALT、AST含量,降低大鼠血清TC、TG、LDL-c,升高HDL-c;对模型SD大鼠肝脏中异常升高的MDA、LDH、LD均有明显的降低作用;形态学检查显示,醇提物高剂组肝脏脂变程度明显减轻,脂滴数量减少,提示该药物具有保肝降脂的药理作用。     

补肾化痰方对去卵巢大鼠血清TRACP5b 和β-CTX 的影响

目的:观察补肾化痰方对去卵巢骨质疏松症大鼠血清脂联素抗酒石酸酸性磷酸酶5b(tartarte-resistant acid phosphatase 5b,TRACP5b)和血清β-I型胶原C-末端肽(C-terminal telopeptides of type I collagen,β-CTX)水平的影响。方法:SD大鼠行双侧卵巢切除术;术后3月以中剂量和高剂量补肾化痰方灌胃给药;术后5月,双能X线骨密度测定仪检测大鼠股骨骨密度,ELISA法检测大鼠血清TRACP5b和β-CTX含量。结果:补肾化痰方中、高剂量组均能显著提高去卵巢骨质疏松症大鼠的骨密度,降低血清TRACP5b和β-CTX水平。结论:补肾化痰方对去卵巢大鼠骨质疏松症有较好的治疗作用。     

补肾化痰方对去卵巢大鼠血清TRACP5b和β-CTX的影响

目的：观察补肾化痰方对去卵巢骨质疏松症大鼠血清脂联素抗酒石酸酸性磷酸酶5b（tartarte-resistant acid phosphatase 5b,TRACP5b）和血清β-I型胶原C-末端肽（C-terminal telopeptides of type I collagen,β-CTX）水平的影响。方法：SD大鼠行双侧卵巢切除术;术后3月以中剂量和高剂量补肾化痰方灌胃给药;术后5月,双能X线骨密度测定仪检测大鼠股骨骨密度,ELISA法检测大鼠血清TRACP5b和β-CTX含量。结果：补肾化痰方中、高剂量组均能显著提高去卵巢骨质疏松症大鼠的骨密度,降低血清TRACP5b和β-CTX水平。结论：补肾化痰方对去卵巢大鼠骨质疏松症有较好的治疗作用。     

左归丸、右归丸对去卵巢骨质疏松模型大鼠的效用

本研究以去卵巢骨质疏松症模型大鼠为研究对象,采用比较分析与去卵巢骨质疏松症相关的多项因子的方法,试图探究左、右归丸的效应机理。将雌性SD大鼠随机分为空白组、假手术组、模型组(OVX组)、己烯雌酚组、左归丸组、右归丸组,每组12只。除空白组、假手术组外,将各组大鼠双侧卵巢切除制备绝经后骨质疏松症大鼠模型。造模一周后,分别给予各组相应的蒸馏水或药物,持续治疗12周。测定各组大鼠腰椎骨密度、血清钙、血清碱性磷酸酶(ALP)含量和大鼠胫骨骨髓中OPG、RANKL、Wnt1蛋白的表达量。与空白组、假手术组相比,模型组大鼠OPG、骨密度均显著下降(p0.01),而ALP、RANKL、Wnt1明显升高(p0.01);各给药组较OVX组,OPG、骨密度不同程度提高,ALP、RANKL、Wnt1则有不同程度降低(p0.05)。结果表明,左、右归丸能够抑制骨吸收,降低骨转化率,使骨形成和骨吸收趋于平衡,可有效防治去卵巢骨质疏松症模型大鼠的骨流失并改善骨组织形态,并且右归丸疗效优于左归丸;本研究为中医防治PMOP提供坚实的实验依据,并从分子水平揭示左、右归丸的治疗机理,推动了左、右归丸治疗PMOP作用机制的研究。     

异甘草酸镁对胆道梗阻致肝损伤肝功能保护作用的动物实验研究

目的:探讨异甘草酸镁注射液对大鼠梗阻性黄疸肝损伤的保护作用。方法:选用健康雄性SD大鼠32只,随机分成4组,每组各8只,分别为胆总管结扎+异甘草酸镁注射液常规剂量组(BMc组);胆总管结扎+异甘草酸镁注射液高剂量组(BMh组);胆总管结扎+0.9%生理盐水注射液组(BN组)和假手术组(Sham组)。BN和Sham组以生理盐水30 mg/kg/日腹腔注射,BMc组以异甘草酸镁30 mg/kg/日腹腔注射,BMh组以异甘草酸镁60 mg/kg/日腹腔注射。术后不同时间对各组大鼠眼眶取血并获得血清。在全自动生化分析仪器检测肝功能指标:丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、直接胆红素(Direct bilirubin,DBil)。结果:BN、BMc和BMh组大鼠在胆管结扎后血清中ALT和AST指标明显升高。随着梗阻时间的增加,BM和BMh组大鼠血清中ALT和AST的水平均明显低于BN组(P0.01),但两组之间并无明显区别。手术后BN、BMc和BMh组大鼠在胆管结扎后血清中D-Bil水平明显高于Sham组(P0.01),但随着梗阻时间的延长,各组间D-Bil的水平变化不明显。结论:异甘草酸镁注射液可以有效降低梗阻性黄疸大鼠血清转氨酶水平,对肝功能有明显的保护作用。     

酶解牛骨肽促进骨骼生长功效的研究

采用低钙鼠粮饲喂Wistar大鼠，造大鼠低钙模型，口服给予模型组大鼠酶解牛骨肽3个月，研究酶解牛骨肽对低钙大鼠促进骨骼生长的作用，测定各实验组大鼠体重指数以及大鼠股骨重量、股骨强度、骨钙含量及血清钙离子含量等多项生理生化指标，同时做体外细胞实验，研究酶解牛骨肽对成骨细胞MC3T3 E1增殖情况的影响。结果表明：酶解牛骨肽对低钙大鼠骨钙含量水平的升高有明显作用（P<0.05），酶解牛骨肽可以在体外促进成骨细胞MC3T3 E1的增长，说明酶解牛骨肽在一定程度上能够促进骨骼生长发育。     

Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats

The purpose of this study was to examine the effects of ENA Actimineral Resource A (ENA-A), seaweed origin alkaline water, on postmenopausal osteoporosis in ovariectomized (OVX) rats. The 12-week old Wistar rats were divided randomly into 4 groups: ovariectomized (OVX), OVX plus 0.5% ENA-A, OVX plus 5% ENA-A and OVX plus 10% ENA-A. A histopathological analysis indicated that ENA-A could prevent OVX-induced bone loss by increasing femur trabecular bone area in a dose-dependent manner. ENA-A significantly (p < 0.05) increased serum estradiol levels, decreased serum osteocalcin activity and suppressed serum pyridinoline (PYD) levels. The in vitro effects of ENA-A were also studied using MC3T3-E1 cells. ENA-A significantly stimulated cell proliferation and increased both ALP activity and calcium deposition in a dose-dependent manner. These results suggest that the treatment of ovariectomized rats with ENA-A not only prevents bone resorption but also appears to maintain the cancellous bone structure of postmeopausal osteoporosis.     

Anti-resorptive effect of pilose antler blood (Cervus nippon Temminck) in ovariectomized rats

Anti-bone resorption activity of pilose antler blood (Cervus nippon Temminck) were evaluated in ovariectomized Wistar rats. The rats were randomly divided into sham operated group (SHAM), ovariectomized group (OVX) and pilose antler blood treated group. The ovariectomized rats were treated with pilose antler blood orally in 4000 microl/kg daily doses for 10 weeks. Compared with SHAM group, serum 17 beta-estradiol level decreased significantly and osteocalcin level increased significantly in OVX group, indicating successful model of osteoporosis. The experiments showed that the bone mineral density of the lumbar spine and left femur in OVX group decreased remarkably compared to SHAM group but normalized by treatment with pilose antler blood. Additionally, serum levels of insulin-like growth factor-land testosterone were lower obviously in OVX group than those in SHAM group but preserved by pilose antler blood treatment. However, no obvious changes in serum levels of calcium, phosphorus, total alkaline phosphatase and osteoprotegerin were observed among three groups. These results suggested that administration of pilose antler blood was effective in alleviating osteoporosis in ovariectomized rats.     

Pulsed electromagnetic fields prevent osteoporosis in an ovariectomized female rat model: a prostaglandin E2-associated process

With the use of Helmholtz coils and pulsed electromagnetic field (PEMF) stimulators to generate uniform time varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on osteoporosis and serum prostaglandin E(2) (PGE(2)) concentration were investigated in bilaterally ovariectomized rats. Thirty-five 3 month old female Sprague-Dawley rats were randomly divided into five different groups: intact (INT), ovariectomy (OVX), aspirin treated (ASP), PEMF stimulation (PEMF + OVX), and PEMF stimulation with aspirin (PEMF + ASP) groups. All rats were subjected to bilateral ovariectomy except those in INT group. Histomorphometric analyses showed that PEMF stimulation augmented and restored proximal tibial metaphyseal trabecular bone mass (increased hard tissue percentage, bone volume percentage, and trabecular number) and architecture (increased trabecular perimeter, trabecular thickness, and decreased trabecular separation) in both PEMF + OVX and PEMF + ASP. Trabecular bone mass of PEMF + OVX rats after PEMF stimulation for 30 days was restored to levels of age matched INT rats. PEMF exposure also attenuated the higher serum PGE(2) concentrations of OVX rats and restored it to levels of INT rats. These experiments demonstrated that extremely low intensity, low frequency, single pulse electromagnetic fields significantly suppressed the trabecular bone loss and restored the trabecular bone structure in bilateral ovariectomized rats. We, therefore, conclude that PEMF may be useful in the prevention of osteoporosis resulting from ovariectomy and that PGE(2) might relate to these preventive effects.     

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。     

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.     

Short-term Administration of Water-soluble Silicon Improves Mineral Density of the Femur and Tibia in Ovariectomized Rats

Silicon is important for the proper growth and development of bone and connective tissues. This study was designed to investigate if water-soluble silicon could be used for the treatment of postmenopausal osteoporosis. Silicon (Si 20 mg/kg body weight/day) was administrated orally to 17-week-old ovariectomized (OVX) rats for 4 weeks. Silicon did not alter weight gain in OVX rats. Silicon supplementation significantly increased the bone mineral density of the femur (p < 0.05, vs. OVX control group) and tibia in OVX rats (p < 0.05, vs. OVX control group). Serum alkaline phosphatase and osteocalcin, two bone formation biomarkers tested, were not significantly altered, but urinary calcium and phosphorous excretion tended to decrease with silicon supplementation. OVX rats with silicon supplementation showed a relatively higher serum CTx compared to the nonsupplemented OVX group (p < 0.01, vs. OVX control group). According to these results, short-term soluble silicon supplementation improved bone mineral density in OVX-induced osteoporosis.     

Role of recombinant plasmid pEGFP-N1-IGF-1 transfection in alleviating osteoporosis in ovariectomized rats

Decreased levels of serum insulin-like growth factor-1 (IGF-1) have been proven to cause osteoporosis. Gene transfer of IGF-1 offers an attractive technology to treat skeletal metabolic disorders including osteoporosis, but the viral vectors are limited by their high antigenicity and immune response. Our purpose was to investigate the expression of a non-invasive vector, recombinant plasmid enhanced green fluorescent protein-N1 (pEGFP-N1) that transferred IGF-1 gene into ovariectomized (OVX) rats in vivo and evaluate the effect of this therapy on osteoporosis. OVX or sham operations were performed in 60 female, 7-month-old unmated SD rats. 12 weeks after OVX operation, the vectors were transfected to the 10-month-old rats and experimental data were detected from 48 h to 7 week after transfection. Our results showed that remarkable expression of fluorescence and serum IGF-1 was observed in the rats transfected by recombinant plasmids, indicating that IGF-1 gene was successfully transferred to OVX rats by injecting the vector through hydrodynamic method via the tail vein. The bone metabolism index including serum alkaline phosphatase, the histomorphometric parameters of lumbar vertebra including trabecular area percentage, trabecular thickness, trabecular number and trabecular separation, and the bone mineral density (BMD) and biomechanical parameters of lumbar vertebra including BMD, maximum condensing force, crushing strength in OVX rats transfected by pEGFP-N1-IGF-1 were improved remarkably compared with OVX+pEGFP-N1 rats, indicating that the transfection of recombinant plasmid pEGFP-N1-IGF-1 played a significant role in alleviating osteoporosis in rats induced by OVX. This encouraged a potential approach of IGF-1 gene therapy to the treatment of osteoporosis.