葛根素联合雌二醇对去卵巢大鼠骨质疏松的治疗作用

目的了解小剂量葛根素联合雌二醇对去卵巢大鼠骨质疏松(OP)治疗作用,为中西医结合治疗Ⅰ型OP提供实验依据。方法 5月龄健康雌性大白鼠120只,分成5个实验组(n=24):①假手术组(sham);②去卵巢模型组(OVX);③葛根素组(Pr),皮下注射葛根素,50 mg/kg,1次/d;④雌二醇组(E2),皮下注射雌二醇200μg/kg,2次/w;⑤小剂量葛根素+雌二醇组(Pr+E2),皮下注射雌二醇100μg/kg,2次/w和葛根素25 mg/kg,1次/d。各实验组在第4、8、12和20周,随机取6只大鼠处死,取左股骨切片观察骨组织,取右股骨测量骨密度(BMD),取左心血测量血清雌二醇(E2)、碱性磷酸酶(AKP)。结果 OVX组的血清E2和BMD明显低于sham组(P<0.01),而血清AKP明显高于sham组(P<0.01);3个治疗组各时间的血清E2、AKP和BMD无显著差异(P>0.05)。小剂量的葛根素联合雌二醇治疗能使去卵巢大鼠骨组织、血清E2、AKP和BMD接近正常(P>0.05),与较大剂量的葛根素组或较大剂量的E2组相比无明显差异(P>0.05)。结论小剂量的E2与葛根素对去卵巢大鼠的治疗效果与单独使用较大剂量的葛根素或较大剂量的E2相比治疗效果相近。     

番茄红素对去卵巢大鼠骨质保护作用的研究

目的 研究去卵巢大鼠体内氧化应激水平和骨质的变化及番茄红素对其影响.方法 将32只雌性SD大鼠随机分成4组:假手术组,模型组,小剂量干预组和大剂量干预组.术后1 w开始用番茄红素灌胃,于术后10 w时处死各组大鼠,并对血生化、氧化及抗氧化指标,骨密度,生物力学等参数进行检测,对其骨组织形态学进行观察.结果 在去势10 w后,与假手术组相比,模型组大鼠血清钙、磷、碱性磷酸酶、丙二醛等均不同程度的升高(P＜0.01,P＜0.05),而血清超氧化物歧化酶水平、骨密度值及生物力学指标均不同程度的下降(P＜0.01,P＜0.05).药物干预组,尤其是大剂量干预组的上述参数指标与模型组相比呈现出显著差异(P＜0.01,P＜0.05).结论 氧化应激可能与骨质疏松的发生相关,并初步证实番茄红素对去势大鼠骨质具有保护作用.     

葛根素对去卵巢大鼠骨质疏松和血脂的作用

激素替代疗法（HRT）对绝经后骨质疏松防治效果肯定，但HRT使心血管疾病发生的相对风险增加22％，对脂代谢影响尚无定论，长期应用可引起子宫内膜癌和乳腺癌。一些植物雌激素具有选择性雌激素受体调节功能，与合成雌激素有相似的抗绝经后骨质疏松作用。葛根素属植物雌激素，有扩张血管、改善心脑供血和抗动脉粥样硬化的作用。近年的研究表明，葛根异黄酮可降低去卵巢大鼠肝内胆固醇（TC）和甘油三酯（TG）水平，体外研究提示葛根素有抑制骨吸收的作用，但葛根素对去卵巢大鼠骨质疏松和血脂代谢的系统研究报道较少。我们对去卵巢大鼠模型给予葛根素，观察骨质疏松大鼠骨密度、骨生物力学指标和血脂的变化。     

密骨胶囊对去卵巢大鼠骨质疏松模型的影响

目的 探讨密骨胶囊对去卵巢骨质疏松模型大鼠腰椎整体骨量和骨质成分丢失的影响。方法 40只10月龄Wistar雌性大鼠随机分为正常组、模型组、密骨胶囊组和倍美力组,每组10只。正常组仅行假手术,其余三组行卵巢切除术。术后91天开始给药,连续用药满90天,处死,取出第2腰椎,测定整体骨量和钙、磷、有机质含量。结果 密骨胶囊能明显提高骨质疏松大鼠腰椎骨的整体骨量和钙、磷、有机质含量。结论 密骨胶囊能增强骨质疏松大鼠腰椎的骨量,改善骨结构。     

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。     

英卡膦酸钠对去卵巢大鼠骨质疏松的作用

目的　观察英卡膦酸钠对去卵巢 (OVX)大鼠骨质疏松症的影响。方法　将 6 1只 6月龄Wistar大鼠分为 8组 :(1)基线组 (n =8)于 6月龄时处死 ;其余大鼠行去卵巢手术或假手术 :(2 )去卵巢后 6周组 (n =8)于去卵巢后 6周处死 ;(3)假手术组 (n =8) ;(4)去卵巢后 14周组 (n =8) ;(5 )去卵巢后雌激素治疗组 (n =9) ;去卵巢后英卡膦酸钠胃肠用药组分为 (6 )低剂量组 (n =6 )、(7)中剂量组 (n =7)和 (8)高剂量组 (n =7)。治疗组自去卵巢后 6周开始共用药 8周。于手术后 14周时处死后 6组大鼠 ,分别留取右侧胫骨、股骨和血尿标本 ,进行骨组织计量学静态和动态指标的分析、股骨远端松质骨外周定量CT检查、股骨远端凹入实验和血尿骨转换指标测定。结果　雌激素和三个英卡膦酸钠治疗组的胫骨近端次级骨小梁体积较去卵巢后 14周组显著增加 (P <0 .0 5或P <0 .0 1) ,伴有骨小梁结构改善。高剂量英卡膦酸钠组的股骨远端松质骨骨密度较去卵巢后 14周组显著增加 (P <0 .0 1) ,其松质骨的最大载荷较去卵巢后 14周组显著升高 (P <0 .0 5 )。英卡膦酸钠的以上作用呈剂量依赖性增加。结论　英卡膦酸钠能有效地治疗OVX大鼠的骨质疏松症。     

山茶籽与葛根素对去卵巢大鼠骨质疏松的防治作用比较

目的探讨山茶籽与葛根素对去卵巢大鼠的骨组织形态结构、骨密度和碱性磷酸酶的影响。方法5月龄雌性大鼠32只,分成4个试验组(每组8只):(1)假手术(Sham)组;(2)去卵巢模型(OVX)组;(3)山茶籽治疗(Ts)组:山茶籽醇提物灌胃,10 ml/kg,1次/d(5 g/g生药);(4)葛根素治疗(Pr)组:皮下注射葛根素,50 mg/kg,1次/d。各试验组在4、12 w,麻醉大鼠采血测定碱性磷酸酶,12 w后处死右侧股骨切片染色镜观骨组织结构,右侧股骨烘干测量骨密度,数据常规计算分析。结果与Sham组比较,OVX组骨组织镜下观骨质疏松明显,血碱性磷酸酶升高明显(P<0.01)。Ts组、Pr组、Sham组骨切片组织结构、骨密度和碱性磷酸酶差异无统计学意义(P>0.05)。结论山茶籽和葛根素对去卵巢大鼠的骨质疏松有防治作用,疗效相近。     

去卵巢所致骨质疏松大鼠骨压缩与冲击力学性能实验研究

目的研究正常鼠和去卵巢所致骨质疏松大鼠骨的压缩、冲击力学性质。方法选用280~320g,10月龄Wistar雌性大鼠20只,随机分为正常对照组10只,模型组10只。对模型组大鼠于0w摘除其卵巢。正常对照组和模型组大鼠饲养14w后,以腹主动脉放血法处死大鼠。取大鼠股骨进行压缩实验,取大鼠胫骨进行冲击实验。结果得出了大鼠股骨压缩力学性能指标和大鼠胫骨冲击力学性能指标。结论模型组压缩和冲击力学性能指标显著降低。     

杜仲叶醇提物对去卵巢大鼠所致骨质疏松的防治作用

目的观察杜仲叶醇提物对去卵巢大鼠骨质疏松(OP)模型的影响,探究杜仲防治OP的作用机制。方法选取10月龄SD雌性大鼠,制作去卵巢大鼠OP模型,分为假手术组、模型组、阿尔法骨化醇(ALF)组、杜仲叶醇组,并观察各组股骨重量、胫骨抗弯力、血清碱性磷酸酶(ALP)的变化。结果与模型组比较,杜仲叶醇组股骨重量明显增加,胫骨抗弯力增强,ALP含量增高(P<0.05);与ALF组无明显差异(P>0.05)。结论杜仲叶醇提物通过提高血清ALP含量,增加股骨重量,提高胫骨抗弯力等因素防治OP。     

补肾中药对去卵巢大鼠骨密度的影响

目的　寻找安全有效的治疗骨质疏松症的药物。方法　通过卵巢摘除 (OVX)建立原发性骨质疏松 (POP)模型 ;研究不同剂量的补肾中药对去卵巢大鼠骨密度的影响。结果　高、中剂量中药组能提高全身各部位的骨量 (与 OVX组比较 P<0 .0 5) ,这种功能与尼尔雌醇作用相当 (P>0 .0 5) ;高、中剂量中药组能提高去卵巢大鼠雌激素水平 ,同时能降低去卵巢大鼠体内 HOP和 AL P水平 (与 OVX组比较 P<0 .0 5)。结论　补肾中药具有提高骨密度的功能 ,其机理与该药具有类雌激素样作用及能同时抑制成骨细胞和破骨细胞的作用     

叶酸缺乏对大鼠同型半胱氨酸水平及动脉损伤的影响

目的观察叶酸缺乏饮食对大鼠血浆同型半胱氨酸(Hcy)水平及动脉组织的影响.方法雄性Wistar大鼠20只均分成2组,分别给予叶酸缺乏(叶酸缺乏组)和叶酸正常(对照组)饲料,饲养3个月后检测血清叶酸和血浆Hcy浓度及红细胞超氧化歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)活力,实验后光镜检查主动脉组织学变化.结果叶酸缺乏组实验后血清叶酸浓度[(6.08±1.84)μg/L]明显低于实验前[(13.32±2.02)μg/L]和对照组[(12.17±1.67)μg/L],而血浆Hcy浓度[(28.66±6.07)μmol/L]明显高于实验前[(9.75±1.86)μmol/L]和对照组[(9.49±1.77)μmol/L,P＜0.01];红细胞SOD[(37389.5±5158.4)NU/g*Hb]高于对照组[(30355.7±6349.2)NU/g*Hb],GPX活力[(10.94±3.05)U/L]低于对照组[(17.93±3.05)U/L,P＜0.05];主动脉组织出现内皮细胞肿胀、变性、脱落,裸露的内膜附有血栓和胶原纤维,内皮下组织疏松并出现平滑肌细胞,内弹力膜断裂,中膜明显增厚.结论叶酸缺乏饮食可引发高Hcy血症和动脉损伤,高Hcy血症诱导体内高氧化应激可能是动脉损伤机制之一.     

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.     

The effect of homocysteine-lowering therapy with folic acid on flow-mediated vasodilation in patients with coronary artery disease: A meta-analysis of randomized controlled trials

Objective

High level of homocysteine induces injury of endothelial cells and predicts adverse cardiovascular events. The objective was to assess the effect of homocysteine-lowering therapy with folic acid on flow-mediated vasodilation in patients with coronary artery disease.

Methods and results

We conducted a meta-analysis of randomized controlled trials identified from PubMed, Embase, the Cochrane Library. Eight studies were included. Homocysteine-lowering therapy with folic acid in patients with coronary artery disease significantly improve FMD as compared with placebo using random-effect model (SMD = 1.65 with 95% CI 1.12–2.17, p < 0.001). Subgroup analysis of subjects revealed that lipid-lowering therapy, study duration, and Delphi criteria had no effects on FMD.

Conclusion

Our meta-analysis demonstrated that folic acid supplementation can significantly improve endothelial dysfunction as assessed by FMD in the brachial artery in patients with coronary heart disease.     

高同型半胱氨酸血症与肺血栓栓塞症的关联及叶酸干预的价值

目的:探讨高同型半胱氨酸血症(hyperhomocysteine,HHcy)是否增加国人肺血栓栓塞症(PTE)的危险,及叶酸干预对PTE患者HHcy的价值。方法:对41例PTE患者应用高效液相色谱法测定血浆同型半胱氨酸(homocysteine,Hcy)水平,设性别、年龄匹配的正常对照34例。HHcy者给予叶酸、维生素B12,10d后复测血浆Hcy。结果:PTE患者血浆Hcy水平明显高于正常对照组[(20.1±7.8)μmol/L和(13.84±4.7)μmol/L,t=4.79,P<0.05)],HHcy使PTE发生的相对危险增加2.44倍,应用叶酸、维生素B12后血浆Hcy水平显著下降。结论:HHcy是国人PTE的独立危险因素。叶酸、维生素B12能有效降低其血浆Hcy水平。     

Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats

Although there is general agreement that thyroid hormone is an important hormonal regulator of testis physiology during development period, its role in the post-pubertal and adult testes is still controversial. Furthermore, most experimental studies to date have focused on thyroid hormone effects on the developing testes and only limited data are available on its role in spermatogenesis. This study evaluated some biochemical alterations in post-pubertal hypothyroidism and its impact on testicular function. Additionally, the ameliorating role of folic acid supplementation was investigated. Fifty male albino rats were randomly divided into five groups (group I, control; group II, folic acid; group III, 0.05% propylthiouracil-induced hypothyroid rats; group IV, co-treatment; group V, post-treatment). Plasma total homocysteine, total NO metabolites, malondialdehyde and GSSG/GSH ratio quantified by HPLC significantly (P < 0.05) increased in hypothyroid rats as compared to controls. These biochemical alterations at least in part disrupted spermatogenesis in these experimental models. Folic acid supplemented after restoration of the euthyroid state (group V) presented better amelioration to spermatogenesis over its concurrent supplementation (group IV). This postulates an indirect negative impact of post-pubertal hypothyroidism on testicular function through development of these alterations. This is plus the observed role of folic acid supplementation in enhancing spermatogenesis, boosting sperm concentration and building up the antioxidant status against the oxidants in the present study. If confirmed in human beings, our results could propose that folic acid can be used as an adjuvant therapy in hypothyroidism disorders with thyroxin replacement therapy.     

Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation

PURPOSE: Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function. SUBJECTS AND METHODS: Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project. All subjects were given folic acid (10 mg/d) for 1 year. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound. RESULTS: Folic acid supplementation for 1 year was associated with a significant increase in mean (+/-SD) plasma folate levels (24 +/- 5 nmol/L to 40 +/- 5 nmol/L; P < 0.001) and a significant decline in homocysteine levels (9.0 +/- 1.7 micromol/L to 7.9 +/- 2.0 micromol/L; P < 0.001). Flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses. CONCLUSIONS: These results demonstrate that long-term folic acid improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with hyperhomocysteinemia.     

Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis

The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3±2.4 µmol/l in group I and 7.87±3.2 µmol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3±15.9 ng/ml and 8.41±2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.This revised version was published in February 2005 with corrections to the authors affiliations and the abstract.     

补肾中药组方对去卵巢大鼠骨微结构的影响

目的研究补肾中药组方对去卵巢大鼠骨微结构的影响。方法通过卵巢摘除建立骨质疏松模型,研究不同剂量的补肾中药对去卵巢大鼠骨微结构的影响。结果光镜下观察高剂量补肾中药组方能改善去卵巢大鼠的骨小梁的分布、排列、之间的连接、厚度及间隙等组织学表现。组织计量学表明高、中剂量中药组能提高骨小梁TBV%和MTT(与OVX组比较P<0.05),这种功能与尼尔雌醇作用相当(P>0.05),低剂量中药组能提高骨小梁TBV%(与OVX组比较P<0.05)。结论补肾中药具有改善去势大鼠骨微结构的功能。