多虑平治疗慢性病贫血的机制研究

An in vivo assay for doxepin in treating anemia of chronic disease

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。

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 3groups：healthy control group,ACD model group and doxepin treatment group,each group had 8rats.After 7days of treatment,peripheral blood was collected for counting hemoglobin（Hb）by automated blood analyzers and the level of serum IL-6was 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-6level（r=0.619）.Compared to ACD model group,serum IL-6levels 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.