目的研究南极磷虾肽(peptide from Antarctic krill,AKP)对双侧去卵巢骨质疏松症模型小鼠肠钙吸收的改善作用。方法对9周龄雌性健康C57BL/6J小鼠进行双侧卵巢摘除手术,建立骨质疏松症模型,术后12周,随机分为假手术组(生理盐水)、模型对...目的研究南极磷虾肽(peptide from Antarctic krill,AKP)对双侧去卵巢骨质疏松症模型小鼠肠钙吸收的改善作用。方法对9周龄雌性健康C57BL/6J小鼠进行双侧卵巢摘除手术,建立骨质疏松症模型,术后12周,随机分为假手术组(生理盐水)、模型对照组(生理盐水)、阳性对照组(阿伦磷酸钠,1mg/kg)、南极磷虾肽组(800mg/kg)。每天灌胃1次,连续灌胃90d后,通过测定血清生化指标PTH、1,25(OH)_2D_3、血钙及血磷以及肠钙吸收通道基因Trpv6、CaBP-d9k、PMCA1b的mRNA表达水平。结果血清结果表明,AKP能够显著抑制血清中PTH的水平,增加1,25(OH)_2D_3的含量,维持血清中钙、磷稳定;qRT-PCR结果表明,AKP能显著上调十二指肠中1,25(OH)2D3的受体VDR以及肠钙吸收通道关键基因Trpv6、CaBP-d9k、PMCA1b的mRNA表达水平,增强去卵巢骨质疏松小鼠的肠钙吸收功能;并且AKP能够显著增加模型组小鼠的骨密度及骨钙、骨磷含量。结论 AKP能够改善去卵巢骨质疏松症小鼠的肠钙吸收作用,增加去卵巢小鼠的骨矿含量。展开更多
Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GS...Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ ab-sorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxida-tive/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca transport or the paracellular Ca route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The favonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety,pharmacokinetics and pharmacodynamics of them.展开更多
文摘目的研究南极磷虾肽(peptide from Antarctic krill,AKP)对双侧去卵巢骨质疏松症模型小鼠肠钙吸收的改善作用。方法对9周龄雌性健康C57BL/6J小鼠进行双侧卵巢摘除手术,建立骨质疏松症模型,术后12周,随机分为假手术组(生理盐水)、模型对照组(生理盐水)、阳性对照组(阿伦磷酸钠,1mg/kg)、南极磷虾肽组(800mg/kg)。每天灌胃1次,连续灌胃90d后,通过测定血清生化指标PTH、1,25(OH)_2D_3、血钙及血磷以及肠钙吸收通道基因Trpv6、CaBP-d9k、PMCA1b的mRNA表达水平。结果血清结果表明,AKP能够显著抑制血清中PTH的水平,增加1,25(OH)_2D_3的含量,维持血清中钙、磷稳定;qRT-PCR结果表明,AKP能显著上调十二指肠中1,25(OH)2D3的受体VDR以及肠钙吸收通道关键基因Trpv6、CaBP-d9k、PMCA1b的mRNA表达水平,增强去卵巢骨质疏松小鼠的肠钙吸收功能;并且AKP能够显著增加模型组小鼠的骨密度及骨钙、骨磷含量。结论 AKP能够改善去卵巢骨质疏松症小鼠的肠钙吸收作用,增加去卵巢小鼠的骨矿含量。
文摘Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ ab-sorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxida-tive/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca transport or the paracellular Ca route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The favonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety,pharmacokinetics and pharmacodynamics of them.