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摘要: 目的: 探讨多虑平治疗大鼠慢性病贫血(ACD)的机制。方法: 将24只大鼠按照随机对照原则共分为3个组:健康对照组、ACD模型组、多虑平治疗组,每组均为8只。药物治疗1周后采集新鲜血液,用自动化血液分析仪测定血常规,ELISA法检测血清中IL-6浓度;取肝组织,用RT-PCR法检测肝脏hepcidin mRNA表达量。结果: ACD模型组血清中IL-6水平、肝脏hepcidin mRNA表达量较健康对照组显著升高(P<0.01),且分别与血红蛋白呈线性负相关(r=-0.591、r=-0.759),肝脏hepcidin mRNA 表达量与血清IL-6水平呈线性正相关(r=0.619)。多虑平治疗组血清IL-6水平、肝脏hepcidin mRNA表达量较ACD模型组均显著下降(P<0.05),血红蛋白明显升高(P<0.01)。结论: 多虑平可改善大鼠ACD,作用机制可能与其通过抑制IL-6水平、降低hepcidin mRNA表达量有关。
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关键词:
- 慢性病贫血 /
- 多虑平 /
- IL-6 /
- hepcidin mRNA
Abstract: Objective: To elucidate the mechanism of doxepin in the treatment of mouse anemia of chronic disease (ACD).Method: A total of 24 male SD rats were randomly divided into 3 groups:healthy control group,ACD model group and doxepin treatment group,each group had 8 rats.After 7 days of treatment,peripheral blood was collected for counting hemoglobin (Hb) by automated blood analyzers and the level of serum IL-6 was detected by ELISA,liver tissues were also collected for assessment of hepcidin mRNA by RT-PCR.Result: Compared to healthy control group,serum IL-6,hepatic hepcidin mRNA expression in ACD model group were significantly increased (P<0.01),and both were negatively correlated with Hb (r=-0.591,r=-0.759).There was a positive correlation betweenhepatic hepcidin mRNA expression and IL-6 level (r=0.619).Compared to ACD model group,serum IL-6 levels and hepatic hepcidin mRNA expression in the doxepin treatment group were significantly decreased (P<0.05),and Hb was increased (P<0.01).Conclusion: Doxepin should alleviate ACD in rats.It might be interpreted by decreasing hepcidin mRNA expression and inhibiting the secretion of IL-6.-
Key words:
- anemia of chronic disease /
- doxepin /
- interleukin-6 /
- hepcidin mRNA
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[1] Qiu MZ,Yuan ZY,Luo HY,et al.Impact of pretreatment hematologic profile on survival of cliorectal cancer patients[J].Tumour Biol,2010,31:255-260.
[2] Zhang Y,Chen Y,Chen D,et al.Impact of preoperative anemia on relapse and survival in breast cancer patients[J].BMC Cancer,2014,14:844.
[3] Rainville N,Jachimowicz E,Wojchowski DM.Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis[J].Expert Opin Ther Targets,2015,30:1-15.
[4] 孙雪峰,周道斌,赵永强.EPO对铁调蛋白hepcidin表达影响的研究[J].中国实验血液学杂志,2006,14(4):778-782.
[5] Eleftheriadis T,Pissas G,Antoniadi G,et al.Kynurenine,by activating aryl hydrocarbon receptor,decreases erythropoietin and increases hepcidin production in HepG2 cells:a new mechanism for anemia of inflammation[J].Exp Hematol,2016,44:60-67.
[6] Vokurka M,Krijt J,Vávrová J,et al.Hepcidin expression in the liver of mice with implanted tumour reacts to iron deficiency,inflammation and erythropoietin administration[J].Folia Biol (Praha),2011,57:248-254.
[7] Altschuler EL,Kast RE.Using histamine (H1) antagonist,in particular atypical antipsychotics,to treat anemia of chronic disease via interleukin-6 suppression[J].Med Hypotheses,2005,65:65-67.
[8] Richelson E.Antimuscarinic and other receptor-blocking properties of antidepressants[J].Mayo Clin Proc,1983,58:40-46.
[9] Ganz T.Hepcidin and iron regulation,10 years later[J].Blood,2011,117:4425-4433.
[10] Rishi G,Wallace DF,Subramaniam VN.Hepcidin:regulation of the master iron regulator[J].Biosci Rep,2015,35:e00192.
[11] Jiang F,Yu WJ,Wang XH,et al.Regulation of hepcidin through GDF-15 in cancer-related anemia[J].Clin Chim Acta,2014,428:14-19.
[12] Przybyszewska J,Zekanowska E.The role of hepcidin,ferroportin,HCP1,and DMT1 protein in iron absorption in the human digestive tract[J].Prz Gastroenterol,2014,9:208-213.
[13] 王恒石,胡喜梅,周水阳,等.血清TNF-α、IFN-γ、IL-6水平与慢性病贫血的关系[J].山东医药,2014,54(45):79-81.
[14] Hohaus S,Massini G,Giachelia M,et al.Anemia in Hodgkin's lymphoma:the role of interleukin-6 and hepcidin[J].J Clin Oncol,2010,28:2538-2543.
[15] Akdis CA,Blaser K.Histamine in the immune regulation of allergic inflammation[J].J Allergy Clin Immunol,2003,112:15-22.
[16] Masuda K,Kimura A,Hanieh H,et al.Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages[J].Int Immunol,2011,23:637-645.
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