药物治疗骨质疏松肱骨拉伸力学特性的对比

背景：力学性能指标是评价药物治疗骨质疏松动物模型效果的重要方法,以拉伸力学性能指标评价多种药物治疗老龄雌性骨质疏松模型大鼠的效果评价罕见报道。 目的：评定中药骨疏康胶囊、西药阿仑膦酸钠、维生素K、钙剂逸得乐对骨质疏松模型大鼠肱骨拉伸力学的影响。 方法：四五个月龄雌性Wistar大鼠180只分为6组,每组30只。除正常对照组外对所有大鼠于0周摘除双侧卵巢制备骨质疏松动物模型。骨疏康胶囊组动物每日给服骨疏康胶囊0.9 g/kg、阿仑膦酸钠治疗组动物每日给服阿仑膦酸钠1 mg/kg、维生素K组动物每日给服维生素K 0.1 mg/kg、钙剂组动物每日给服钙剂逸得乐2 mg/kg。15周后取大鼠左、右侧肱骨在电子万能试验机上以5 mm/min的实验速度进行拉伸实验,试样破坏后观察试样的断口形貌。 结果与结论：骨质疏松动物模型组大鼠肱骨拉伸实验最大载荷、最大应变显著小于正常对照组和骨疏康胶囊组、阿仑膦酸钠组、维生素K组(P < 0.05);钙剂组最大载荷,最大应力,最大应变和模型组差异不显著(P > 0.05)。结果说明,中药、西药、维生素K治疗骨质疏松模型大鼠拉伸力学性能均有一定提高,中药骨疏康胶囊治疗骨质疏松模型大鼠拉伸力学性能明显提高。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

四种药物治疗骨质疏松模型大鼠股骨扭转力学特性对比

背景：骨质疏松的预防、诊断和治疗都需要了解药物治疗的效果。扭转力学性能指标是对药物治疗后骨质疏松质量评价的一种可靠方法。 目的：观察不同药物治疗动物骨质疏松的疗效。 方法：四五月龄雌性Wistar大鼠建立骨质疏松模型,以复方中药、阿仑膦酸钠、维生素K、钙剂进行治疗,饲养15周后处死大鼠,取大鼠股骨在扭转试验机上以1 (°)/s进行扭转实验,实验结束后通过试验机测量变盘读取转矩和扭转角数据,试样破坏后观察试样的断口形貌。 结果与结论：骨质疏松大鼠最大转矩、扭转角、切应力均低于正常大鼠(P < 0.05),而经过复方中药或阿仑膦酸钠治疗后,最大转矩、扭转角、切应力得到恢复,但维生素K及钙剂治疗效果不明显。说明中药、西药、维生素K治疗动物骨质疏松模型大鼠均有一定疗效,钙剂效果不明显,中药的效果最好。     

阿仑膦酸钠可抑制骨质疏松性骨折的愈合

背景：阿仑膦酸钠作为治疗骨质疏松症的首选药物已被临床广泛应用。 目的：观察阿仑膦酸钠对骨质疏松性骨折大鼠股骨干骨折愈合的影响。 方法：将SD大鼠随机分成3组：假手术组,模型组和阿仑膦酸钠组。模型组及阿仑膦酸钠组于卵巢切除后4周进行右股骨干中段横行骨折,克氏针固定。阿仑膦酸钠组建模后皮下注射阿仑膦酸钠。 结果与结论：骨折造模后3及6周,阿仑膦酸钠组右股骨整体骨密度和远段骨密度高于模型组(P < 0.01),与模型组相比,阿仑膦酸钠组骨折端骨痂体积大、骨痂数量多,软骨性骨痂向骨性骨痂转换过程延迟,骨折愈合过程减慢,破骨细胞数量显著降低(P < 0.05)。结果证实,阿仑膦酸钠对大鼠骨质疏松性骨折愈合过程有抑制作用,其机制可能与阿仑膦酸钠抑制破骨细胞活性使骨痂钙化过程减慢有关。     

阿仑膦酸钠与雷洛昔芬对牙槽骨吸收的影响

背景：研究证明阿仑膦酸钠与雷洛昔芬对骨质疏松有抑制作用。 目的：建立实验性大鼠骨质疏松及牙槽骨吸收模型,评价阿仑膦酸钠与雷洛昔芬对骨吸收的防治作用。 方法：56只雌性SD大鼠建立骨质疏松及牙槽骨吸收的动物模型,实验动物分组：①去势+结扎组和单纯结扎组又分别分为3个亚组：阿仑膦酸钠组、雷洛昔芬组和非用药组。②单纯去势非用药组。③假手术组做空白对照。建模手术后第5日开始灌胃给药,1次/d,治疗3个月。用血生化指标、骨密度测量及组织形态学方法进行药效评价。 结果与结论：阿仑膦酸钠治疗组较雷洛昔芬组有更强的降低去势组碱性磷酸酶和血钙的作用;提高去势组骨密度。结果证实阿仑膦酸钠与雷洛昔芬均能减少骨质丢失,从而可以防止骨质疏松及病理性牙槽骨骨吸收,且阿仑膦酸钠作用较好。     

阿仑膦酸钠改善去卵巢大鼠的骨基质结构

背景：双膦酸盐可以提高骨密度、抑制骨吸收的作用已被临床所证实,但其对于骨骼基质结构的影响研究较少。 目的：实验通过观察双膦酸盐类药物——阿仑膦酸钠对骨结构及骨基质代谢的影响,探讨阿仑膦酸钠改善骨质量、提高骨强度的骨基质调控机制。 方法：实验建立去卵巢大鼠模型,用阿仑膦酸钠进行干预,同时设置模型组和假手术组进行对照。运用骨骼影像学、骨组织病理学和骨生物力学检测技术与酶联免疫吸附法观察阿仑膦酸钠对骨丢失大鼠骨密度、骨代谢、骨生物力学性能和骨结构的影响。 结果与结论：药物干预后4,8,12周,阿仑膦酸钠组骨密度均高于模型组(P < 0.05);药物干预8周后,与模型组相比,阿仑膦酸钠组骨代谢指标尿脱氧吡啶诺啉,血清Ⅰ型胶原羧基端前肽水平均降低(P < 0.05),腰椎和股骨的最大载荷、最大压强、模量以及Ⅰ型胶原不同交联形式的尿吡啶啉/脱氧吡啶啉值均增高(P < 0.05)。结果证实,阿仑膦酸钠能够对抗因雌激素缺乏导致大鼠骨量的丢失,提高生物力学性能,改善骨基质结构,同时恢复因去卵巢所导致的Ⅰ型胶原交联组分的改变。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

不同药物治疗原发性骨质疏松症的网状Meta分析

文题释义：阿仑膦酸钠：属于双膦酸盐类药物,可以通过多种作用机制治疗骨质疏松,通过抑制破骨过程,维持骨结构,改善骨矿化程度,有效增加骨皮质的厚度和骨密度,从而提高人体骨骼强度,减轻和预防骨质疏松。 钙剂：通常把以钙元素的生理生化功能及药理学作用为基础、以钙盐为主要成分的制剂称为钙剂。钙剂产品常见为片剂、胶囊、冲剂、粉剂、溶液、针剂等剂型。 背景：临床研究发现阿仑膦酸钠联合降钙素类、钙剂类等其他药物治疗原发性骨质疏松症能提高疗效、降低其不良反应发生率,但尚乏系统评价。 目的：系统评价不同药物治疗原发性骨质疏松症的临床疗效、骨密度、安全性的差异。 方法：计算机检索PubMed、CNKI、VIP、万方数据库、Embase、CBM、Cochrane图书馆,收集不同药物治疗原发性骨质疏松的随机对照试验(RTC)。文献筛选,数据提取,采用Cochrane系统评价及RevMan 5.3对纳入文献进行质量评价;运用马尔科夫链-蒙特卡洛方法,采用Stata 15.0进行贝叶斯网状Meta分析。结果与结论：①共纳入14项RCT,共计1 822例患者,涉及阿仑膦酸钠、唑来膦酸、钙剂、钙剂联合唑来膦酸、阿仑膦酸钠联合钙剂、阿仑膦酸钠联合骨肽注射液、钙剂联合骨肽注射液、阿仑膦酸钠联合特立帕肽注射液、鲑鱼降钙素等9种干预措施;②在提高总有效率方面,共涉及9种干预措施,网状Meta排序结果为钙剂联合骨肽注射液>阿仑膦酸钠联合骨肽注射液>阿仑膦酸钠联合唑来膦酸>唑来膦酸>唑来膦酸联合钙剂>鲑鱼降钙素>阿仑膦酸钠联合钙剂>阿仑膦酸钠>钙剂;③在提高治疗后骨密度方面,共涉及5种干预措施,网状Meta排序结果为阿仑膦酸钠联合钙剂>钙剂>钙剂联合唑来膦酸>唑来膦酸>阿仑膦酸钠;④在降低不良反应发生率方面,共涉及7种干预措施,网状Meta排序结果为钙剂>阿仑膦酸钠联合钙剂>阿仑膦酸钠联合骨肽注射液>唑来膦酸联合钙剂>唑来膦酸>阿仑膦酸钠>阿仑膦酸钠联合特立帕肽注射液;⑤结论：骨肽注射液的联合用药能显著提高治疗总有效率,其中钙剂联合骨肽注射液效果最佳;钙剂在提高治疗后骨密度的疗效确切,而联合阿仑膦酸钠具有增效作用,且不良反应的发生率较低,效果最好。ORCID: 0000-0002-4976-9599(阙敏强) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

4种药物干预治疗骨质疏松模型大鼠骨三点弯曲力学特性的对比分析

背景：力学性能指标是评价药物治疗骨质疏松动物模型效果的重要方法,以3点弯曲力学性能指标评价多种药物治疗老龄雌性骨质疏松模型动物的效果鲜有报道。 目的：以大鼠骨3点弯曲力学性能指标评价骨质疏松模型大鼠经丹杞颗粒、结合性雌激素、依普拉芬及αD3干预的效果。 方法：Wistar雌性大鼠48只分为6组,除正常组外,采用以去双侧卵巢的方法复制老龄骨质疏松大鼠模型。丹杞颗粒干预组每日给服丹杞颗粒0.9 g/kg,普拉芬干预组每日给服依普拉芬1 mg/kg,αD3干预组每日给服αD3 0.1 mg/kg,结合型雌激素干预组每日给服结合型雌激素0.3 mg/kg。以电子万能实验机对各组大鼠左、右侧胫骨进行3点弯曲力学性能测试。 结果与结论：丹杞颗粒、依普拉芬、结合型雌激素干预组胫骨最大载荷、最大应力、最大弯矩、最大应力及弹性模量大于模型组(P < 0.05);αD3干预组最大载荷、最大应力、最大应变、弹性模量与模型组差异无显著性意义(P > 0.05);丹杞颗粒干预组胫骨最大载荷、最大应力、最大应变与正常对照组比较差异无显著性意义(P > 0.05)。丹杞颗粒干预组、结合型雌激素干预组、依普拉芬干预组弯曲力学性能恢复较好,以丹杞颗粒干预组效果最好,αD3干预治疗组弯曲力学性能指标无明显恢复。结果说明以丹杞颗粒干预骨质疏松模型大鼠胫骨3点弯曲力学性能恢复效果最好。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

阿仑膦酸钠治疗骨质疏松模型大鼠机制的串联质量标签蛋白质组学分析

背景：目前关于阿仑膦酸钠治疗骨质疏松症的作用机制及作用靶点，仍需深入研究。目的：探究阿仑膦酸钠调节骨质疏松模型大鼠骨代谢的作用机制，并进行差异表达蛋白生物信息学分析。方法：雌性SD大鼠随机分为模型组、阿仑膦酸钠组、假手术组，每组12只，前两组均采用去卵巢法建立骨质疏松症模型，造模4周后阿仑膦酸钠组大鼠予阿仑膦酸钠灌胃；另外两组予等体积生理盐水。连续灌胃12周后测定胫骨骨密度，采用串联质量标签联合液相色谱-串联质谱法联用技术对大鼠腰椎进行蛋白质组学分析，筛选出差异表达蛋白，并进行基因本体、京都基因和基因组百科全书通路及蛋白相互作用网络分析。结果与结论：(1)筛选出阿仑膦酸钠组与模型组组间上调/下调差异表达蛋白分别为32个/51个；(2)基因本体富集分析结果显示，差异表达蛋白主要参与结合、催化活性等分子功能以及细胞过程、代谢过程等生物过程；(3)京都基因和基因组百科全书富集分析结果显示，阿仑膦酸钠组/模型组组间差异表达蛋白功能主要参与泛酸和辅酶A的生物合成过程；(4)蛋白相互作用分析结果表明，阿仑膦酸钠组/模型组组间共同差异表达蛋白中Hspa1l、Enpp3、Unc45a、Myh9、Can...     

甲状旁腺素和二膦酸盐对骨密度和骨生物力学的影响

目的:研究应用甲状旁腺素和阿仑膦酸钠对激素性骨质疏松兔骨密度和生物力学的影响。方法:采用成年新西兰大白兔,随机分为对照组、激素模型组、甲状旁腺素和阿仑膦酸钠治疗组,9周后取股骨和腰椎行超声骨密度测量,再行股骨扭转、三点弯曲和腰椎压缩试验。结果:激素模型组的宽频超声衰减(BUA)、超声传导速度(SOS)值和骨生物力学参数较对照组有非常明显减少,甲状旁腺素和阿仑膦酸钠治疗组的BUA、SOS值和骨生物力学参数较激素模型组明显增加。结论:序贯应用甲状旁腺素和阿仑膦酸钠可以减少激素性兔骨量的丢失,预防骨质疏松的发生。     

补肾壮骨方干预去卵巢骨质疏松模型大鼠骨代谢及骨密度的变化

背景：中医药以其良好的治疗效果及安全性越来越多的应用于骨质疏松症的治疗中,补肾壮骨方目前作为山东中医药大学附属医院协定方被广泛应用于临床中,获得了极好的治疗效果。目的：评价补肾壮骨方对去卵巢骨质疏松大鼠骨代谢及骨密度的影响。方法：60只SD大鼠随机分为6组,分别为假手术组、模型组、阿仑膦酸钠组、补肾壮骨方高、中、低剂量组,每组10只,后5组制备去卵巢骨质疏松症模型,假手术组只切除卵巢周围脂肪组织。造模8周后,补肾壮骨方高、中、低剂量组分别予以2.34,1.17,0.58 g/(kg·d)补肾壮骨方,阿仑膦酸钠组予阿仑膦酸钠1 mg/(kg·d),假手术组及模型组给予等体积的生理盐水,1次/d灌胃。连续灌胃12周后检测各组大鼠血清碱性磷酸酶、Runt相关转录因子2及核因子κB受体活化因子配体水平;取右侧股骨观察骨密度及骨微结构;苏木精-伊红染色观察组织病理改变;免疫组化法检测骨组织Wnt1、骨形态发生蛋白2蛋白表达。结果与结论：(1)造模8周后,与假手术组对比,模型组大鼠骨密度、骨小梁数明显降低(P <0.05),提示造模成功;(2)与模型组大鼠对比,补肾壮骨方低、中、高剂量组及阿...     

The effect of a bisphosphonate on bone volume and eggshell structure in the hen

Bisphosphonates, used in the prevention and treatment of osteoporosis, in man, can prevent bone loss in experimental models of osteoporosis in mammals. In egg-laying hens there is a high incidence of bone fractures which are due to osteoporosis. Alendronate, a bisphosphonate, was given to three groups of hens in mid-lay. Different doses of alendronate were given to each group and group 4 was a control. The birds were killed after 2 weeks of treatment. The hens receiving the highest dosage of alendronate (1 mg/kg every 2nd day) ceased laying and had reduced serum calcium concentrations. Lower dosages of alendronate (0.1 and 0.01 mg/kg every 2nd day) resulted in normal egg production and serum calcium concentrations. Egg shells with ultra-structural features indicative of reduced shell quality were produced by hens on the two higher dosages, but the egg shells from the controls and from the hens on the lowest dosage were considered normal. When alendronate was administered to hens in mid-lay there was no effect on trabecular bone volumes, but there was a reduction in mean medullary bone volume in some groups. In a second experiment, pullets were treated with alendronate (0.01 mg/kg twice a week) before the onset of lay. The pullets were killed after laying their first egg. In the pullets treated with alendronate, this protocol resulted in a significantly greater volume of trabecular (structural) bone at the onset of lay.     

Effects of alendronate and hormone replacement therapy, alone or in combination, on bone mass in postmenopausal women with osteoporosis: a prospective, randomized study

The effectiveness of hormone replacement therapy (HRT) and alendronate, alone and in combination, was evaluated in 120 postmenopausal patients with osteoporosis with bone mineral density (BMD) measurements at least 2 SD below the mean value for young premenopausal subjects. They had no contra-indications to HRT or alendronate use and were randomized to three different treatment groups. Group I was treated with micronized 17 beta-oestradiol 2 mg and norethisterone acetate 1 mg/day per os, group II received alendronate 10 mg/day per os and group III received micronized 17 beta-oestradiol 2 mg, norethisterone acetate 1 mg/day per os and alendronate 10 mg/day per os for 1 year. Elementary calcium 1500 mg/day was supplied to patients in all three groups. Spinal and femoral neck BMD and markers of bone mineral metabolism were measured on each patient before treatment and 6 and 12 months after treatment in 95 patients. At the end of the 12th month, significant increases in spinal and femoral neck BMD were found in all groups. Increases in spinal BMD were significantly higher in patients treated with alendronate and alendronate with HRT when compared with patients treated with HRT only. No significant difference was found in femoral neck BMD changes between the groups. Significant decreases in bone resorption and markers of bone formation were observed in all groups. Alendronate was found to be more effective than HRT and could have a very beneficial effect when added to the HRT regimen in patients with postmenopausal osteoporosis. Alendronate might also be used in postmenopausal patients with osteoporosis when HRT is contra-indicated or when there is reluctance to use hormonal treatment.     

Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old

There are inconsistent findings on the effects of vitamin K on bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC). The present intervention study evaluated the effect in subjects over 60-yr-old. The vitamin K group (vitamin K + vitamin D + calcium supplement; 15 mg of vitamin K2 [menatetrenone] three times daily, 400 IU of vitamin D once a day, and 315 mg of calcium twice daily) and the control group (vitamin D + calcium supplement) were randomly assigned. During the six months of treatment, seventy eight women participated (38 in the vitamin K group and 40 in the control group) and 45 women completed the study. The baseline characteristics of study participants did not differ between the vitamin K and the control groups. In a per protocol analysis after 6 months, L3 bone mineral density has increased statistically significantly in the vitamin K group compared to the control group (0.01 ± 0.03 g/cm(2) vs -0.008 ± 0.04 g/cm(2), P = 0.049). UcOC concentration was also significantly decreased in the vitamin K group (-1.6 ± 1.6 ng/dL vs -0.4 ± 1.1 ng/dL, P = 0.008). In conclusion, addition of vitamin K to vitamin D and calcium supplements in the postmenopausal Korean women increase the L3 BMD and reduce the UcOC concentration.     

雌激素与葛根素组合治疗去卵巢大鼠骨症的最佳剂量

背景：小剂量的葛根素联合雌二醇对去卵巢大鼠骨质疏松症的治疗效果与单独使用较大剂量的葛根素或较大剂量的雌二醇效果相近。 目的：寻找治疗Ⅰ型骨质疏松症最佳的雌二醇和葛根素的剂量搭配。 方法：64只健康雌性大白鼠等分为假手术组、去卵巢模型组、葛根素-50组、雌二醇-200组、葛根素+雌二醇-5,50,100,150组。除假手术组外,其余大鼠均建立去卵巢动物模型。葛根素-50组大鼠皮下注射葛根素50 mg/kg,1次/d;雌二醇-200组大鼠皮下注射雌二醇200 μg/kg,2次/周;葛根素+雌二醇-5,50,100,150组大鼠皮下注射葛根素25 mg/kg,1次/d同时分别注射雌二醇5,50,100,150 μg/kg,2次/周。 结果与结论：去卵巢模型组大鼠骨密度和骨钙、骨磷水平明显低于假手术组(P < 0.05),骨组织呈骨质疏松的病理改变;葛根素和/或雌二醇治疗10,20周后骨密度和骨钙、骨磷水平明显升高(P < 0.05),其中葛根素+雌二醇-100组治疗去卵巢大鼠骨质疏松的效果最为明显,提示葛根素25 mg/kg,1次/d+雌二醇100 μg/kg,2次/周是治疗去卵巢大鼠骨质疏松的最佳搭配剂量。     

Synergistic Antiosteoporotic Effect of Lepidium Sativum and Alendronate in Glucocorticoid-Induced Osteoporosis in Wistar Rats

Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who suffer from osteoporosis. Yet, bisphosphonate have displayed several side effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine to heal fractured bones. However, there is a dearth of information on the impact of LS on bone metabolism especially in cases of glucocorticoids induced osteoporosis. Therefore, the aim of the study was to compare the biochemical bone markers and histological responses of LS alone (6 g of LS seeds in diet daily, n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum P and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicated an osteoporotic change and a concomitant decrease in percentage of trabecular area or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or ALD ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals treated with alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health.     

苯妥英钠致大鼠骨质疏松模型的建立及维生素D预防作用的观察

目的：研究苯妥英钠致骨质疏松作用及维生素D的预防作用。方法：将40只SD雄性大鼠随机分为4组(苯妥英钠模型组、D–半乳糖模型组、维生素D预防组、正常对照组),每组10只。其中,用苯妥英钠对苯妥英钠模型组及维生素D预防组大鼠连续灌胃60 d [54 mg/(kg?d)]。60 d后,对苯妥英钠模型组、D–半乳糖模型组、维生素D预防组和正常对照组的相关指标进行检测及比较组间差异。结果：苯妥英钠模型组骨钙[(592.87±120.89)μg]、磷[(173.88±15.98)μg]及血清钙[(2.65±0.09) mmol/L]、磷[(2.13±0.29) mmol/L]、超氧化物歧化酶[(104.40±3.58) NU/mgPro]含量均比正常对照组显著降低(P<0.01),血清碱性磷酸转移酶[(136.00±1.82) U/L]与正常对照组相比有显著升高(P<0.01),骨羟脯氨酸含量[(1128.974±460.77)μg],虽缺乏统计意义但相比于正常对照组仍有所降低,上述变化与D–半乳糖模型组的变化趋势相同,并比后者的变化更加显著。结论：长期大量摄入苯妥英钠可以导致大鼠发生骨质疏松的可能性增加,维生素D可以阻止或减缓这种变化趋势。     

慢性阻塞性肺疾病模型大鼠肺组织基质金属蛋白酶9及组织金属蛋白酶抑制剂1与固本颗粒胶囊

背景:中医药防治慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)的有效性和安全性已初步得到临床认证。 目的：观察COPD模型大鼠肺组织中基质金属蛋白酶9及其特异性抑制物组织金属蛋白酶抑制剂1表达与固本颗粒胶囊干预的影响。 方法：将50只Wistar大鼠随机等分为5组,除正常组外,其余大鼠均以烟熏及气管内滴注脂多糖的方式建立COPD模型。造模   29 d,泼尼松组、固本颗粒胶囊低、高剂量组分别灌胃给予醋酸泼尼松            1.04 mg/(kg•d),固本颗粒胶囊0.47,0.94 g/(kg•d),1次/d,观察记录大鼠的一般状况。免疫组织化学方法检测大鼠肺组织中基质金属蛋白酶9及组织金属蛋白酶抑制剂1的表达。 结果与结论：COPD大鼠肺组织中基质金属蛋白酶9及组织金属蛋白酶抑制剂1的表达显著增强(P < 0.05)。药物干预后,COPD大鼠的一般状况明显改善,肺组织中基质金属蛋白酶9及组织金属蛋白酶抑制剂1的表达有所降低;其中,醋酸泼尼松的作用最为显著,固本颗粒高剂量次之,低剂量最弱。说明固本颗粒胶囊能以剂量依赖的方式缓解COPD大鼠的临床表现,改善气道重塑,纠正COPD大鼠体内蛋白酶和抗蛋白酶失衡。     

Differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed normal or low calcium diet

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25 micro g/100 g, food intake), or vitamin K + vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.