仙珍骨宝对实验性骨质疏松大鼠的骨密度和生物力学影响

目的　探讨仙珍骨宝对糖皮质激素 (GC)所致大鼠骨骼的骨密度和生物力学影响。方法　采用 3月龄雄性 SD大鼠 2 8只 ,随机分为基础对照组、年龄对照组、激素模型组和仙珍骨宝治疗组。后 2组均灌喂醋酸泼尼松 4.5 mg/kg,2次 /w;而仙珍骨宝治疗组同时灌喂仙珍骨宝胶囊(5ml/kg· d- 1 )。 3个月后取股骨和 L5椎体行骨密度测定和股骨的力学性能检测。结果　激素模型组股骨和腰椎的骨密度与年龄对照组比较 ,均出现显著下降 ;股骨干除三点弯曲试验所承受的载荷明显减少 1 7.1 % (P<0 .0 5)外 ,其余的力学参数都有减少的趋势。应用仙珍骨宝治疗后能防止 GC所致的骨密度和力学性能下降。结论　长期使用 GC会使大鼠股骨和腰椎的骨密度和力学性能下降 ,应用仙珍骨宝能扭转类固醇性骨密度和力学性能下降。     

雷洛昔芬对骨保护蛋白基因缺失小鼠的抗骨质疏松作用

目的 利用骨保护蛋白(osteoprotegerin,OPG)基因剔除小鼠模型研究选择性雌激素受体调节剂雷洛昔芬对雌鼠和雄鼠的抗骨质疏松作用.方法 取二月龄OPG基因剔除(OPG-/-)的雌鼠和雄鼠各20只.随机分为雷洛昔芬组(3 mg·kg-1·d-1)和安慰剂组,另取野生犁雌鼠10只作为对照组,1个月后杀鼠取材.测量骨密度、骨生物力学、骨形态计量学,并进行骨组织病理学检查及破骨细胞染色,评价雷洛昔芬的疗效.结果 OPG-/-小鼠呈现明显的骨质疏松表型.雷洛昔芬组的雌鼠较安慰剂组腰椎、股骨骨密度明显增高(均P<0.05);骨生物力学结果显示腰椎和股骨最大载荷(P<0.05或P<0.01),弹性模鼍(P<0.05或P<0.01),结构韧性(均P<0.01)均增高,提示骨折风险性下降;破骨细胞染色示腰椎和股骨破骨细胞面积明显减少(均P<0.01);HE染色示骨小梁数目增加,连接性上升;骨形态计量学结果显示骨形成率降低(P<0.05).雷洛昔芬组的雄鼠与安慰剂组相比较无上述改变.结论 选择性雌激素受体调节剂雷洛昔芬在OPG基因缺失的情况下仍可改善雌鼠骨质疏松,其作用不完全依赖于OPG基因.雷洛昔芬对OPG-/-雄鼠无效.     

去卵巢大鼠股骨和腰椎骨生物力学特性及骨矿物含量的变化

目的比较去卵巢大鼠股骨和腰椎的骨生物力学特性及骨矿物含量的不同。方法10.5月龄未交配的雌性SD大鼠40只,随机分为10.5月龄基础对照组;13月龄假手术组;13月龄去卵巢10 w组;16月龄假手术组;16月龄去卵巢22 w组。大鼠行双侧卵巢去除术后,然后灌喂生理盐水5 m l.kg-1.d-1。大鼠处死后采用三点弯曲试验测定股骨和压缩试验测定腰椎的骨生物力学指标,然后分别测量股骨和腰椎的骨矿物质含量。结果去卵巢大鼠腰椎的骨破坏荷载、破坏应力、弹性模量均明显降低及骨钙、骨磷、骨镁含量均明显降低,但股骨生物力学参数和矿物质含量均无明显变化。结论去卵巢大鼠腰椎的骨生物力学和骨矿物含量均明显降低,而股骨变化不明显。     

强骨宝对去势大鼠骨形态计量学影响的研究

目的 观察强骨宝（黄芪＋司坦唑醇,JGB）对去卵巢大鼠骨质疏松症骨形态计量学参数的影响.方法 取32只Wistar雌性大鼠随机分为4组,行去势手术,制成去卵巢大鼠骨质疏松模型.然后分别灌胃给药生理盐水、己烯雌酚、强骨宝,8 w后处死,取大鼠胫骨上段松质骨和中段皮质骨硬组织包埋、切片,图像分析松质骨、皮质骨形态计量学参数.结果 强骨宝可使去卵巢大鼠松质骨静态参数和动态参数显著增加,吸收参数显著降低;皮质骨面积、骨髓腔面积等静态及内外骨膜骨形成动态参数均无显著变化,内膜面骨吸收参数降低.结论 强骨宝能有效预防去卵巢大鼠骨质疏松症松质骨丢失,亦具有抑制皮质骨内膜骨吸收的作用.     

大鼠骨基质形态增龄性改变及其与骨代谢指标的相关性研究

目的　研究大鼠增龄过程中骨基质形态计量改变规律及与骨代谢指标相关性。　方法　 3、9、15个月龄雌性SD大鼠各 10只。第 4腰椎及右侧胫骨上段作形态计量学分析。物理密度法测定股骨及腰椎骨密度 (BMD)。第 3腰椎作抗压缩试验。自动分析仪测定血清钙、磷 ,放免法测定1,2 5 (OH) 2 D3 。　结果　与 3月龄组比较 ,15月龄组第 4腰椎骨小梁体积减小 4 3 3% (P <0 0 1) ,胫骨上段骨小梁体积减小 2 8 0 % (P <0 0 1) ,骨形成表面降低 17 2 % (P <0 0 5 ) ,骨吸收表面增加39 8% (P <0 0 1) ,腰椎、股骨BMD分别下降 7 7% (P <0 0 1)和 7 3% (P <0 0 1)。骨小梁体积与腰椎BMD、最大载荷、血清 1,2 5 (OH) 2 D3 呈明显正相关 (r =0 6 84、0 972及 0 86 6 ,P <0 0 0 1)。血清 1,2 5 (OH) 2 D3 与胫骨骨形成表面及矿化沉积率呈明显正相关 (r =0 5 87,r =0 6 2 8,P <0 0 1)。　结论　 15月龄雌性SD大鼠骨形成减弱 ,骨吸收增加 ,骨量减少 ,骨结构改变 ,生物力学性能降低。骨形态计量学指标与腰椎BMD和骨生物力学指标有明显的相关性。     

骨质疏松对骨生物力学性能影响实验研究

目的 研究正常大鼠股骨和维甲酸所致骨质疏松大鼠股骨的生物力学性能，为诊断和治疗骨质疏松提供生物力学参数。方法 对正常大鼠股骨和维甲酸所致骨质疏松大鼠股骨进行骨密度测量，对其胫骨制作脱钙切片组织形态观察。还对正常对照组和模型组股骨进行拉伸、扭转、剪切、冲击实验研究。结果 正常对照组拉伸破坏载荷、强度极限、弹性模量；扭转破坏扭矩、扭转角、扭转剪切强度极限；剪切破坏载荷、剪切强度极限；冲击功、冲击韧性指标大于模型组。结论 模型组的各项力学性能指标显著降低。     

强骨宝对去卵巢大鼠骨生物力学及骨量指标的影响

目的观察强骨宝复方制剂干预去卵巢骨质疏松模型大鼠股骨骨生物力学性能参数和骨矿元素钙、镁、磷及羟脯氨酸含量的变化,并探讨两者变化的相互关系。方法取32只Wistar雌性大鼠随机分为4组,按要求行去势手术后分别灌胃给药,8w后处死,取大鼠左侧股骨进行三点弯曲实验,测定股骨生物力学性能参数;取右侧股骨烘干测定钙、镁、磷及羟脯氨酸含量。结果强骨宝可使去卵巢大鼠股骨生物力学性能参数结构和材料力学指标均显著增加（P〈0.01,P〈0.05）;骨干重、羟脯氨酸、钙、镁等骨量指标亦明显提高（P〈0.01,P〈0.05）。结论强骨宝能促进骨羟脯氨酸的合成,钙、镁、磷的吸收和沉积,导致骨量增加;同时能促进骨的结构和材料力学特性的改善,增加骨对外界应力的对抗作用,而且骨生物力学参数与骨量指标两者的变化统一。     

腺嘌呤诱导肾性骨病大鼠模型的生物力学分析

目的:观察腺嘌呤诱导的慢性肾脏病(CKD)肾性骨病大鼠模型的腰椎及股骨的生物力学特点。方法:20只雄性SD大鼠分为正常对照组和CKD组。第6周末处死大鼠,行血清生化标志物检测,取股骨和第五腰椎做骨密度(BMD)及骨生物力学分析。结果:在第6周末,CKD组大鼠血清尿素氮、血清肌酐、血清无机磷、血清甲状旁腺激素较正常对照组均明显升高,血清钙明显降低。与正常对照组比较,CKD组的股骨和第五腰椎椎体BMD均明显降低。骨生物力学,股骨三点弯曲实验结果提示,CKD组大鼠的股骨结构力学指标和材料力学指标均明显降低;腰椎压缩实验结果提示,CKD组大鼠腰椎的结构力学指标和材料力学指标均明显降低。结论:腺嘌呤诱导的大鼠CKD模型能较好地模拟CKD时出现的高转运肾性骨病的生物力学特征,表现为皮质骨和松质骨材料力学和结构力学性能的下降,有望成为CKD肾性骨病模型的研究载体。     

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。     

抗骨松颗粒对去卵巢大鼠骨质含量和生物力学的影响

目的 探讨抗骨松颗粒对去卵巢大鼠骨质疏松模型骨质含量和骨生物力学性能的影响.方法 40只10月龄Wistar雌性大鼠随机分为对照组、模型组、抗骨松组和倍美力组,每组10只.正常对照组做假手术,其余3组做卵巢切除术.术后3个月开始给药,连续用药满90 d,处死动物,取出第2腰椎和股骨,测定骨密度、钙、磷、锰、镁、羟脯氨酸、碱性磷酸酶和有机质含量;取出第3腰椎,测骨质含量和生物力学性能.结果 抗骨松颗粒能明显提高骨质疏松大鼠的骨密度、钙、锰、镁、羟脯氨酸和有机质含量,增强腰椎骨的抗压生物力学性能.结论 应用抗骨松颗粒可以明显改善去卵巢大鼠骨质疏松模型骨质含量和骨的生物力学性能.     

Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1

BACKGROUND & AIMS: Long-term and excessive ethanol intake results in decreased plasma and hepatic levels of retinoic acid (RA), the most active derivative of vitamin A. The decrease of RA by ethanol treatment has been proposed to be a cytochrome P450 enzyme (CYP)-dependent process. However, the role of the major ethanol-induced CYP, CYP2E1, in the metabolism of RA has not been defined. METHODS: In vitro incubations of RA with microsomal fractions of liver tissue containing CYPs from either ethanol-exposed or non-ethanol-exposed rats were carried out using chemical inhibitors and antibodies against various CYPs. In vivo, both ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole, a specific CYP2E1 inhibitor, for 1 month. RA and its catabolic metabolites were analyzed by high-performance liquid chromatography and spectral analysis. RESULTS: Incubation of RA with the liver microsomal fraction from ethanol-exposed rats resulted in greater disappearance of RA and increased appearance of 18-hydroxy-RA and 4-oxo-RA compared with control rat liver microsomal fractions. The enhancement of RA catabolism by ethanol was inhibited by both CYP2E1 antibody and specific inhibitors (allyl sulfide and chlormethiazole) in a dose-dependent fashion, whereas the metabolism of RA into polar metabolites was abolished completely by nonspecific CYP inhibitors (disulfiram and liarozole). Furthermore, treatment with chlormethiazole in ethanol-fed rats in vivo restored both hepatic and plasma RA concentrations to normal levels. CONCLUSIONS: Ethanol-induced CYP2E1 plays a major role in the degradation of RA, which may provide a possible biochemical mechanism for chronic and excessive ethanol intake as a risk for both hepatic and extrahepatic cell proliferation and carcinogenesis.     

缺氧性腺泡内肺动脉构形重组的形态定量研究

目的观察中药黄芪对缺氧性肺动脉高压及肺腺泡内动脉结构改建的抑制作用。方法６０只大白鼠随机分成缺氧组、缺氧＋黄芪组、正常对照组（各组２０只）。缺氧组、缺氧＋黄芪组大鼠在常压缺氧（１０％Ｏ２１０小时／天）下喂养，在实验第１５天、３０天每组分别取１０只进行右心室收缩压、右心室肥大指数测定后处死，再对肺腺泡内动脉进行光镜、电镜观察及形态学定量分析。结果在实验第３０天后，右心室收缩压，在缺氧组高于缺氧＋黄芪组１８倍（Ｐ＜０．０５），右心室肥大指数，在缺氧组高于缺氧＋黄芪组１３倍（Ｐ＜０．０５），腺泡内动脉中层厚度高于缺氧＋黄芪组２３倍（Ｐ＜０．０５）；肺腺泡内动脉外膜单位面积的纤维母细胞数（密度）在缺氧组是１３１±０３（Ｐ＜０．０５），在缺氧＋黄芪组是７６０±０１９（Ｐ＜０．０５）。结论黄芪抑制了肺腺泡内动脉壁细胞增生及扩张肺动脉，黄芪在抑制肺动脉高压结构改建中可能起重要作用     

卡托普利对糖尿病大鼠早期肾小球血流动力学及血中抗坏血酸消耗的效应

观察了Ｃａｐｔｏｐｒｉｌ对ＳＴＺ－糖尿病大鼠肾小球滤过率（ＧＦＲ）、血清中剩余的抗坏血酸（ＲＡ）水平和脂质过氧化物（ＬＰＯ）含量的短期效应。糖尿病组的ＧＦＲ和ＬＰＯ较对照组显著升高，ＲＡ则显著降低；经Ｃａｐｔｏｐｒｉｌ治疗２周后可见上述变化明显被逆转。提示Ｃａｐｔｏｐｒｉｌ对糖尿病早期肾小球血流动力学改变有防止作用，这可能与其具有清除自由基的能力有一定的关系。     

Amelioration of collagen-induced arthritis in rats by nanogold

OBJECTIVE: Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen-induced arthritis (CIA) in rats. METHODS: Binding of 13-nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF-induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) in the ankle joints were determined. RESULTS: Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF-induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold-treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFalpha and IL-1beta were also significantly reduced in the ankle joints of nanogold-treated rats. CONCLUSION: Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.     

Association of arthritis with a gene complex encoding C-type lectin-like receptors

OBJECTIVE: To identify susceptibility genes in a rat model of rheumatoid arthritis (RA) and to determine whether the corresponding human genes are associated with RA. METHODS: Genes influencing oil-induced arthritis (OIA) were position mapped by comparing the susceptibility of inbred DA rats with that of DA rats carrying alleles derived from the arthritis-resistant PVG strain in chromosomal fragments overlapping the quantitative trait locus Oia2. Sequencing of gene complementary DNA (cDNA) and analysis of gene messenger RNA (mRNA) expression were performed to attempt to clone a causal gene. Associations with human RA were evaluated by genotyping single-nucleotide polymorphisms (SNPs) in the corresponding human genes and by analyzing frequencies of alleles and haplotypes in RA patients and age-, sex-, and area-matched healthy control subjects. RESULTS: Congenic DA rats were resistant to OIA when they carried PVG alleles for the antigen-presenting lectin-like receptor gene complex (APLEC), which encodes immunoregulatory C-type lectin-like receptors. Multiple differences in cDNA sequence and mRNA expression precluded cloning of a single causal gene. Five corresponding human APLEC genes were identified and targeted. The SNP rs1133104 in the dendritic cell immunoreceptor gene (DCIR), and a haplotype including that marker and 4 other SNPs in DCIR and its vicinity showed an indication of allelic association with susceptibility to RA in patients who were negative for antibodies to cyclic citrullinated peptide (anti-CCP), with respective odds ratios of 1.27 (95% confidence interval [95% CI] 1.06-1.52; uncorrected P = 0.0073) and 1.37 (95% CI 1.12-1.67; uncorrected P = 0.0019). Results of permutation testing supported this association of the haplotype with RA. CONCLUSION: Rat APLEC is associated with susceptibility to polyarthritis, and human APLEC and DCIR may be associated with susceptibility to anti-CCP-negative RA.     

The new antirheumatic drug KE-298 suppresses monocyte chemoattractant protein (MCP)-1 and RANTES production in rats with adjuvant-induced arthritis and in IL-1β-stimulated synoviocytes of patients with rheumatoid arthritis

We analyzed the effects of the new antirheumatic drug KE-298 on monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) production in rats with adjuvant-induced arthritis and in interleukin (IL)-1beta-stimulated rheumatoid arthritis (RA) synoviocytes. In rats with adjuvant-induced arthritis, the enhanced production of MCP-1 and RANTES and the development of arthritis were suppressed by oral treatment with 100 mg/kg per day of KE-298 for 18 days. Furthermore, KE-298 (10-100 microg/ml) suppressed MCP-1 and RANTES production by IL-1beta-stimulated RA synoviocytes through inhibition of NF-kappaB and AP-1 activation. These results suggest that the inhibitory effect of KE-298 on MCP-1 and RANTES production might partly explain its efficacy in rats with adjuvant-induced arthritis and in patients with RA.     

Inducibility of atrial fibrillation caused by acute increase of atrial pressure in rat diseased heart with chronic atrial dilation

Although acute atrial dilation facilitates the induction of atrial fibrillation (AF) in the normal heart, little is known about whether the induction of AF due to acute atrial dilation increases in the diseased heart. To clarify this, we compared the inducibility of AF by an acute increase of atrial pressure with and without chronic atrial dilation induced by volume- and pressure-overload in rats. Eight weeks after creating abdominal aortocaval shunt and aortic constriction rats (LVH rats, n = 8) or sham rats (n = 8), the hearts were perfused in Langendorff's manner. Right atrial (RA) pressure was increased from 2 cm H2O to 10 cm H2O by the height of the reservoir. Inducibility of AF was evaluated by 5 times burst pacing from the right atrium, and mean cycle length of AF (CL) and the atrial effective refractory period (AERP) were also measured. The inducibility of AF increased from 5 ± 3% at 2 cm H2O to 50 ± 5% at 10 cm H2O RA pressure in sham rats (P < 0.01), but not in LVH rats (20 ± 7% to 25 ± 6%, NS). Mean CL and AERP in LVH rats were longer than those in sham rats. In addition, the AERP decreased with an increase in RA pressure from 2 cm H2O to 10 cm H2O in sham rats, but not in LVH rats. The inducibility of AF caused by an acute increase of RA pressure did not increase in the diseased heart, suggesting that electrophysiological remodeling may play a role, at least in a compensated state, for the prevention of AF due to an acute increase of atrial pressure.     

Chronic modifications of lung and heart development in glucocorticoid-treated newborn rats exposed to hyperoxia or room air

We assessed the mechanics and morphology of the lung in 165 rats treated neonatally with either room air (RA), O₂, RA + steroids, or O₂, + steroids. Newborn Sprague-Dawley male rats were randomly assigned to these groups. O₂,-exposure (0.96-1.0 FiO₂ lasted 5 days, and dexamethasone treatment consisted of eight daily S.C. injections of drug or buffer in successive doses of 0.5,0.4.0.3,0.2,0.1, 0.1. 0.1. and 0.1 mg/kg. At 58 days, right ventricular systolic pressure (RVP) was measured. At 60 days, all rats were sacrificed for obtaining lung weight and DNA, saline pressure-volume (P-V) curves, and morphometry. We weighed right ventricles (RV) and left ventricles + septa (LV). Hyperoxia alone did not, but steroid decreased survival rate to 79.4% (95.3% in RA rats, P < 0.02). Only 21 of 40 (52%) O₂ + steroids rats survived, less than in both RA groups (P < 0.001). RV weight, RVP and muscularization of alveolar duct arteries were significantly increased in O₂ vs. RA rats. In RA + steroids rats, weight of the LV was decreased but RV, RVP, and lung vasculature were not affected. These effects were additive in the O₂ + steroid group. Wet lung weights and DNA were increased for RA + steroid rats over all others. O₂ and steroids shifted the P-V curve to the left and O₂+ steroids still further. Maximal lung volume increased significantly with RA + steroids and still further in O₂ + steroids but not in O₂ alone. O₂ and steroids significantly increased the mean linear intercept and O₂ + steroids even more so. In O₂- and steroid-treated rats, the parenchymal air space increased. In conclusion, both neonatal hyperoxia and steroid administration caused aberrations in the growth of lung and connective tissue. The effects of the two were additive. The vascular system, maximal lung volume, and DNA responded differently, presumably by different modes of action. Pediatr Pulmonol. 1993; 16:81–88. © 1993 Wiley-Liss, Inc.     

Elevation of retinyl ester level in the lungs of rats following repeated intraperitoneal injections of retinoic acid or retinoyl glucuronide

Retinoic acid (RA) is involved in the development of both the conducting airway and alveolar portions of the lung. RA plays a key role in the induction of the formation of alveolar septa. Retinoyl beta-glucuronide (RAG), an endogenous retinoid, acts like RA, but is much less cytotoxic. We examined the effect of daily intraperitoneal doses of RA and RAG (1.66 micromol/kg) in dimethyl sulfoxide (DMSO) and cotton seed oil on the stores of retinol and retinyl ester (RE) in the lung of rats. In two separate experiments, one involving normal rats, and the other involving elastase-treated rats, there was up to a 9-fold increase in REs content in the lungs of rats that received RA or RAG for 12 days as compared to Control rats. The accumulation was most profound when RA was injected in DMSO and least when RAG was injected in cotton seed oil. The reason for the accumulation of REs in the lung is not clearly known.