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维生素K2及其配伍制剂抗实验性骨质疏松症的筛选研究 被引量:1

Anti-osteoporotic screening study of vitamin K2 and its compatibility of medicines
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摘要 目的对由维生素K2、柠檬酸钙、天然维生素E、维生素D3及辅酶Q10配伍形成的14个受试品进行抗去卵巢大鼠高转换型骨质疏松症作用筛选。方法 14个受试品均由昆明云大医药开发有限公司配制提供,具体为:受试品1:维生素K2(80μg/kg)、受试品2:维生素K2(80μg/kg)+辅酶Q10(50 mg/kg)、受试品3:维生素K2(50μg/kg)+柠檬酸钙(500 mg/kg)、受试品4:维生素K2(80μg/kg)+柠檬酸钙(500 mg/kg)、受试品5:维生素K2(50μg/kg)+维生素D3(4μg/kg)、受试品6:维生素K2(80μg/kg)+维生素D3(4μg/kg)、受试品7:维生素K2(50μg/kg)+维生素E(40 mg/kg)、受试品8:维生素K2(80μg/kg)+维生素E(40 mg/kg)、受试品9:维生素K2(50μg/kg)+维生素E(40 mg/kg)+维生素D3(4μg/kg)、受试品10:维生素K2(80μg/kg)+维生素E(40 mg/kg)+维生素D3(4μg/kg)、受试品11:维生素K2(50μg/kg)+维生素E(40 mg/kg)+柠檬酸钙(500 mg/kg)、受试品12:维生素K2(80μg/kg)+维生素E(40 mg/kg)组+柠檬酸钙(500 mg/kg)、受试品13:维生素K2(50μg/kg)+维生素D3(4μg/kg)+柠檬酸钙(500 mg/kg)、受试品14:维生素K2(80μg/kg)+维生素D3(4μg/kg)+柠檬酸钙(500 mg/kg)。采用去卵巢(ovariectomy,OVX)方法复制大鼠骨质疏松症模型。动物随机分为:正常对照组、假手术组(未切卵巢)、去卵巢模型组、30μg/kg己烯雌酚阳性药物对照组和14个受试品组。受试品以1 mL/100 g体重每日灌胃1次,连续60 d;正常对照组动物灌胃生理盐水,连续60 d;假手术组和模型组均灌胃给予花生油,连续60 d。末次给药后采用双能X线检测股骨和腰椎的骨密度(bone mineral density,BMD)及骨矿含量(bonemineral content,BMC)、原子吸收检测股骨骨钙水平。结果 (1)对BMD及BMC的影响:与模型组比较,受试品13和14可明显升高股骨和椎骨的BMD及BMC(与模型组比较,P<0.01),且受试品14的作用强于受试品13(与受试品13比较,P<0.05)。受试品1及由其配伍的受试品2、4、6、8、10、12均可增加股骨和椎骨的BMD及BMC(P<0.05,与模型组比较)。受试品5和9可以增加股骨和椎骨的BMD及BMC(P<0.05,与模型组比较),其作用与受试品1、2、4、6、8、10、12基本相当。与模型组比较,受试品3、7和11仅增加椎骨的BMD,对股骨BMD无明显影响。(2)对股骨重量和骨钙水平的影响:与模型组比较,受试品13和14显著增加股骨的湿重、干重、灰重,明显提高骨钙水平,与模型组比较,P<0.01,且受试品14强于受试品13;受试品1及由其配伍的受试品2、4、6、8、10、12、受试品5和9均明显增加股骨的湿重、干重、灰重,同时可提高骨钙水平,且作用相当。受试品3、7和11虽然可增加股骨的湿重和干重,但对灰重尤其是骨钙水平均无明显影响。结论在本实验条件下,14个受试品中,受试品13和14作用较强,且受试品14强于受试品13;受试品1、2、4、5、6、8、9、10、12、13具有基本相当的抗骨质疏松症作用,但均弱于受试品14;在本实验条件下,受试品3、7、11无明显作用。从组分配伍来分析,80μg/kg的维生素K2及其配伍制剂均具有明显的增加骨密度和骨钙作用,其中配伍的维生素D3和柠檬酸钙具有明显的协同增效作用;本研究所用剂量的维生素E或辅酶Q10并不能明显提高维生素K2的抗骨质疏松作用。 To screen the anti-osteoporotic activity of 14 samples, which were consisted of vitamin K2, calcium citrate, natural vitamin E, vitamin D3, and coenzyme Q10, in osteoporotic model rats with high turnover osteoporosis induced by ovariectomy. Methods All the 14 samples were provided by the Pharmaceutical Development Company Limited of Yunnan University, including sample 1 : vitamin K2 (80 g/kg) , sample 2: vitamin K2 (80 g/kg) + coenzyme Q10 (50 mg/kg) , sample 3 : vitamin K2 (50 g/kg) + calcium citrate (500 mg/kg) , sample 4 : vitamin K2 (80 g/kg) + calcium citrate (500 mg/kg), sample 5: vitamin K2 (50 g/kg) + vitamin D3 (4 g/kg) , sample 6: vitamin K2 (80 g/kg) + vitamin D3 (4 g/kg), sample 7: vitamin K2 (50 g/kg) + vitamin E (40 mg/kg), sample 8: vitamin K2 (80 g/kg ) + vitamin E (40 mg/kg), sample 9: vitamin K2 (50 g/kg) + vitamin E (40 mg/kg) + vitamin D3 (4 g/kg), sample 10: vitamin K2 (80 g/kg) + vitamin E (40 mg/kg) + vitamin D3 (4 g/kg) , sample 11 : vitamin K2 (50 g/kg ) + vitamin E (40 mg/kg) + calcium citrate (500 mg/kg), sample 12: vitamin K2 (80 g/kg ) + vitamin E (40 mg/kg) + calcium citrate (500 mg/kg), sample 13: vitamin K2 (50 g/kg) + vitamin D3 (4 g/kg) + calcium citrate (500 mg/ kg) , and sample 14: vitamin K2 (80 g/kg) + vitamin D3 (4 g/kg) + calcium citrate (500 mg/kg). Female Sprague- dawly rats were randomly divided into normal control group, sham operation group, and ovariectomized (OVX) group. Rat osteoporosis model was established using OVX. Rats in OVX group were then randomly divided into model group, 301xg/kg diethylstilbestro] positive control group, and the above 14 test sample groups, respectively. Rats in 14 test sample groups were given a lmL/100g administration of the samples intragastrically once a day, lasting for 60 days. Normal saline was used in normal control group, and peanut oil was used in sham and model groups, respectively. The detailed grouping was shown in Table 1. Bone mineral density (BMD) and bone mineral content (BMC) were examined by dual-energy X-ray absorptiometry analysis, and bone calcium by atomic absorption, respectively. Results Effect on BMD and BMC: as compared with that in model group, test sample 13 and 14 could significantly improve BMD and BMC of the femur and the vertebrae ( P 〈 0. 01 ). The effect of test sample 14 was stronger than that of test sample 13 ( P 〈 0. 05 ). Test sample 1 and test samples 2, 4, 6, 8, 10, and 12 (combined with the same dose of test sample 1 ) could increase BMD and BMC of the femur and the vertebrae (P 〈0.01). Test sample 5 and 9 obtained the similar effect to those of test samples 1 , 2, 4, 6, 8, 10, and 12. As compared with model group, test samples 3, 7, and II only improved BMD of the vertebrae, but had no effect on BMD of the femur. Effect on femur weight and bone calcium: as compared with that in model group, test samples 1, 2, 4, 5, 6, 8, 9, 10, 13, and 14 markedly increased the wet, dry and ash weight of the femur, and elevated the level of bone calcium. Among them, test sample 14 showed the highest activity (P 〈 0.05). Test samples 3, 7 and 11 increased the wet and dry weight, but had no significant effect on ash weight or bone calcium. Conclusion Among all the 14 provided samples, test sample 14 shows the strongest anti-osteoporotic effect. Test samples 1, 2, 4, 5, 6, 8, 9, 10, 12 andl3 have the similar activity, but inferior to test sample 14. Test samples 3, 7 or 11, however, have no significant anti- osteoporotic activity.
出处 《中国骨质疏松杂志》 CAS CSCD 北大核心 2013年第5期500-508,共9页 Chinese Journal of Osteoporosis
关键词 维生素K2 柠檬酸钙 天然维生素E 维生素D3 辅酶Q10 骨质疏松症 骨密度 骨矿含量 骨钙 Vitamin K2 Calcium citrate Natural vitamin E Vitamin D3 Coenzyme Q10 Osteoporosis Bone mineraldensity Bone mineral content Bone calcium
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参考文献12

  • 1Koshihara Y, Hoshi K. Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res, 1997,12:431-438.
  • 2Takeuehi Y, Suzawa M, Fukumoto S, et al. Vitamin K2 inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures. Bone, 2000, 27:769-776.
  • 3Takee A, Hirano J, Uchikura C, et al. Effects of drug treatment on bone strength and structural changes with aging: an experimental study in rats. J Orthop Sci, 2002, 7 (5) :544-548.
  • 4Zou ZQ, Fu SC, Liu ZH. The research progress of vitamin K2. Chin J Osteoporos,2005,11 ( 3 ) :389-392.
  • 5Michelle M, Aixu S, Zhou CC,et al. Vitamin K2 regulation ofbone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem, 2003, 278 (45) :43919-43927.
  • 6Tomoe I, Kuniko HI, Kazuhiro I. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extraeellular matrix-related genes and collagen accumulation in osteoblastlc cells. J Bio Chem, 2006, 281 (25) : 16927-16934.
  • 7Reddi K, Henderson B, Meghji S, el al. lnterleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone ( vitamin K) compounds. Cytokine, 1995, 7:287-290.
  • 8Wnelan AM, Jurgens TM, Bowles SK. Natural health products in the prevention and treatment of osteoporosis: systematic review of randomized controlled trials. Ann Pharmacother, 2006, 40:836- 849.
  • 9Koshihara Y, Hoshi K, Shiraki M. Enhancement of minertalization on human osteoblasts by vitamin K2 (menaquinone 4). J Clin Exp Med, 1992, 16!. :439-440.
  • 10Hara K, Akiyama Y, Tomiuga T, et al. Influence of vitamin D3 on inhibitory effect of vitamin K2 on bone lose in ovarieetomized rats. Folia Pharmacol Jpn, 1994, 104:101-109.

同被引文献16

  • 1邹志强 ,符诗聪 ,刘忠厚 .维生素K2的研究进展[J].中国骨质疏松杂志,2005,11(3):389-392. 被引量:31
  • 2World health organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO technical report series 843. Geneva: world health organization, 1994.
  • 3Schapira C, Slinn S, Sarid M. Calcium and vitamin D enriched diets increase and preserve vertebral mineral content in aging laboratory rats [J]. Bone, 1995, 16: 575-582.
  • 4J. C. Gallagher, B. Lawrence Riggs, John Eisman, et al. Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients [ J]. J Clin Invest, 1979, 64: 729-736.
  • 5Tobias Alfvn, Carl-Gustaf Elinder, Margareta Dea Carlsson, et al. Low-level cadmium exposure and osteoporosis [ J]. Journal of Bone and Mineral Research, 2000, 15: 1579-1586.
  • 6B. E. Christopher Nordin, M D, FRCP. Calcium and osteoporosis [J]. Nutrition, 1997, 13: 664-686.
  • 7P. Weber. The role of vitamins in the prevention of osteoporosis- a brief status report [ J]. International Journal for Vitamin and Nutrition Research, 1999, 69: 194-197.
  • 8Liman Sun, Hajime Tamaki. Inhibition of osteoporsis induced by protein deficient food intake by active vitamin D3 and vitamin Kz in Rats [J]. Biosci. biotechnol. Biochem. , 2004, 68: 1385-1387.
  • 9Yuji Kasukawa, Naohisa Miyakoshi, Toshihito Ebina, et al. Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis [ J]. Journal of Bone and Mineral Metabolism, 2014, 32: 290-297.
  • 10Masayoshi Yamaguchi, Emi Sugimoto, Sachiko Hachiya. Stimulatory effect of menaquinone-7 ( vitamim K2 ) on osteoblastic bone formation in vitro [ J ]. Molecular and Cellular Biochemistry, 2001, 223: 131-137.

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