Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron...Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.展开更多
背景:膝骨关节炎多发于中老年人,是一类严重影响患者的生活质量甚至有致残风险的疾病。因此,膝骨关节炎的发病机制以及治疗手段已成为研究的焦点。在祖国医学中,膝骨关节炎常以“痹”论治,并与中医“血瘀”理论中血行瘀滞、血脉阻络而...背景:膝骨关节炎多发于中老年人,是一类严重影响患者的生活质量甚至有致残风险的疾病。因此,膝骨关节炎的发病机制以及治疗手段已成为研究的焦点。在祖国医学中,膝骨关节炎常以“痹”论治,并与中医“血瘀”理论中血行瘀滞、血脉阻络而致之“痹”紧密相关。铁超载是一类因铁代谢紊乱导致的病理状态,其与中医“血瘀”理论的发病特点、临床表现等高度重合,是促进膝骨关节炎发展的危险因素。目的:基于“血瘀”理论,就铁超载对软骨代谢以及软骨下骨重建的影响展开综述,为中医药治疗膝骨关节炎奠定了全新理论基础,也为探究活血中药干预骨组织后期治疗作用的相关机制提供理论依据。方法:通过检索中国知网、万方数据、PubMed及Web of Science数据库获得文献,中文检索词为“铁死亡,铁,铁超载,骨关节炎,血瘀”以及英文检索词为“ferroptosis,iron,iron overload,osteoarthritis,TCM”,最终纳入文献76篇进行综述分析。结果与结论:①文章针对“血瘀”理论治疗膝骨关节炎的潜力进行发掘,发现“血瘀”是膝骨关节炎进展中至关重要的部分,表明“血瘀”理论是中医治疗膝骨关节炎的关键所在。②“血瘀”与铁超载在致病因素、临床表现、发病特点上有高度的相似性,提示了“血瘀”理论治疗铁超载的可能性,说明铁超载可能是“血瘀”理论治疗膝骨关节炎的重要机制基础,活血类药物的提取物有着缓解铁超载并治疗膝骨关节炎的作用,但具体机制尚不明确。③“血瘀”理论与铁超载的关系及相关机制是未来膝骨关节炎的重要研究方向,可为中医临床开发新药、创新用法等中医现代化手段提供了理论基础,对临床有一定的指导意义。展开更多
基金Supported by Royal Golden Jubilee Ph D Program of Thailand Research Fund(Grant No.PHD/0345/2552)Faculty of Medicine Research Fund,Chiang Mai University,ThailandChair Professor Grant of National Science and Technology Development Agency through Professor Suthat Fucharoen,MD
文摘Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.
文摘背景:膝骨关节炎多发于中老年人,是一类严重影响患者的生活质量甚至有致残风险的疾病。因此,膝骨关节炎的发病机制以及治疗手段已成为研究的焦点。在祖国医学中,膝骨关节炎常以“痹”论治,并与中医“血瘀”理论中血行瘀滞、血脉阻络而致之“痹”紧密相关。铁超载是一类因铁代谢紊乱导致的病理状态,其与中医“血瘀”理论的发病特点、临床表现等高度重合,是促进膝骨关节炎发展的危险因素。目的:基于“血瘀”理论,就铁超载对软骨代谢以及软骨下骨重建的影响展开综述,为中医药治疗膝骨关节炎奠定了全新理论基础,也为探究活血中药干预骨组织后期治疗作用的相关机制提供理论依据。方法:通过检索中国知网、万方数据、PubMed及Web of Science数据库获得文献,中文检索词为“铁死亡,铁,铁超载,骨关节炎,血瘀”以及英文检索词为“ferroptosis,iron,iron overload,osteoarthritis,TCM”,最终纳入文献76篇进行综述分析。结果与结论:①文章针对“血瘀”理论治疗膝骨关节炎的潜力进行发掘,发现“血瘀”是膝骨关节炎进展中至关重要的部分,表明“血瘀”理论是中医治疗膝骨关节炎的关键所在。②“血瘀”与铁超载在致病因素、临床表现、发病特点上有高度的相似性,提示了“血瘀”理论治疗铁超载的可能性,说明铁超载可能是“血瘀”理论治疗膝骨关节炎的重要机制基础,活血类药物的提取物有着缓解铁超载并治疗膝骨关节炎的作用,但具体机制尚不明确。③“血瘀”理论与铁超载的关系及相关机制是未来膝骨关节炎的重要研究方向,可为中医临床开发新药、创新用法等中医现代化手段提供了理论基础,对临床有一定的指导意义。
