慢性病性贫血患者低分子肝素治疗的临床和实验研究

Clinical and Experimental Study on Low Molecular Weight Heparin in Patients with Anemia of Chronic Diseases

目的研究低分子肝素(LMWH)治疗慢性病性贫血(ACD)患者前后血红蛋白(Hb)水平以及血清诱导铁调素(Hepcidin),IL-6和骨形态发生蛋白6(BMP6)的变化情况及临床意义。方法 61例ACD患者应用LMWH(4 000 u/天,共7~15天)治疗,同时应用ELISA法测定治疗前后血清Hepcidin和BMP6,应用电化学发光法测定IL-6,并分析其可能的作用机制。结果①61例患者治疗后Hepcidin为0.82±0.24 mg/L,低于治疗前1.05±3.83 mg/L,差异有统计学意义(t=2.5726,P<0.05),治疗后IL-6为24.88±12.58 mg/L,也明显低于治疗前38.22±31.23 mg/L,差异有统计学意义(t=2.9650,P<0.05);而Hb和BMP6两者则无明显差异。但贫血组患者治疗后Hb水平高于治疗前(t=1.983 2,P<0.05)。②肿瘤贫血组治疗后Hb水平为91.18±15.91 g/L,高于治疗前的85.45±18.33 g/L,差异有统计学意义(t=1.971 1,P<0.05)。③肿瘤贫血组治疗后Hepcidin和IL-6分别为0.73±0.45 g/L和30.33±28.39 mg/ml,均低于治疗前的1.09±0.41 g/L和50.76±42.10 mg/ml,差异有统计学意义(分别为t=3.394 1,P<0.01和t=2.359 7,P<0.05),而BMP6差异则无统计学意义(P>0.05)。④肿瘤无贫血组各项指标差异均无统计学意义。⑤非肿瘤贫血组虽然Hb水平略有升高,但无统计学意义,其余各项指标差异均无统计学意义。⑥肿瘤组患者治疗后Hb水平与Hepcidin,IL-6均呈负相关(分别为r=-0.280 9,t=2.249 0,P<0.05和r=-0.278 1,t=2.226 6,P<0.05)。Hepcidin与IL-6呈正相关(r=0.294 1,t=2.362 2,P<0.05)。BMP6与Hb,Hepcidin和IL-6水平均无相关关系。结论 LMWH可以改善患者的贫血。其可能的机制为下调IL-6和Hepcidin的表达,但与BMP6无关。

Objective To preliminary study the significance of low molecular weight heparin(LMWH) in the treatment the patients of anemia of chronic diseases(ACD),and the changes of the serum levels of BMP6,hepcidin and IL-6.Methods Used LMWH(4 000 u/day,7~15 days) to therapy 61 patients with ACD,and ELISA method was used to determine Hepcidin and BMP6 before and after treatment,and determination of IL-6 by Electrochemiluminescence,and to analyse its clinical significance.Results ①In all 61 cases,the levels of Hepcidin in post-therapy were 0.82±0.24 mg/L,which were lower than 1.05±3.83 mg/L in pretherapy(t=2.572 6,P<0.05).The levels of IL-6 in post-therapy were 24.88±12.58 mg/L,which were lower than 38.22±31.23 mg/L in pretherapy(t=2.965 0,P<0.05),but there were not statistically significant both Hb and BMP6 between in pretherapy and post-therapy(all P>0.05).However,the levels of Hb in post-therapy were higher than in pretherapy(t=1.983 2,P<0.05).②After treatment,the level of Hb in tumor anemia group was 91.18±15.91 g/L,which was higher than 85.45±18.33 g/L(t=1.971 1,P<0.05) in pretherapy.③Hepcidin and IL-6 after treatment in tumor anemia group were respectively 0.73±0.45 mg/L and 30.33±28.39 mg/ml,which were lower than 1.09±0.41 mg/L and 50.76±42.10 mg/ml respectively(t=3.394 1,P<0.01 and t=2.359 7,P<0.01) pretherapy.But BMP6 was not statistically significant(all P>0.05).④There was no statistical significance in all indexes of tumor without anemia(P>0.05).⑤The level of Hb increased slightly in the non tumor anemia group,but there was no statistical significance(P>0.05).The remaining indicators were not statistically significant(all P>0.05).⑥After treatment,the level of Hb was negatively correlated with Hepcidin and IL-6(respectively r=-0.280 9,t=2.249 0,P<0.05 and r=-0.278 1,t=2.226 6,P<0.05).Hepcidin was positive related to IL-6(r=-0.294 1,t=2.362 2,P<0.05).There was no correlation between BMP6 and Hb, Hepcidin and IL-6 levels.Conclusion LMWH could up-regulate the levels of Hb,and better for the degree of anemia in patients with ACD.The possible mechanism is to reduce the level of Hepcidin and IL-6.