基于红细胞溶血贫血探讨地中海贫血患者证候季节变化的生物学机制

Biological Mechanism of Symptoms Seasonal Variation Based on Erythrocyte Hemolysis Anemia in Patients with Thalassemia Disease

目的从地中海贫血患者红细胞溶血贫血探讨证候季节变化及证候季节变化的生物学机制。方法在夏季(7月份)和冬季(11月份)分别对11例中间型地中海贫血患者(5例α-地中海贫血、6例β-地中海贫血)的中医证候进行量化评分,并检测患者血液参数[血红蛋白(Hb)、红细胞(RBC)、网织红细胞(Ret)]水平的差异。检测冬夏两个月份患者血清造血相关细胞因子[干细胞因子(SCF)、白介素-3(IL-3)、促红细胞生成素(EPO)]的活性水平的差异;检测冬夏两个月份红细胞抗氧化损伤指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)]的活性水平的差异;检测冬夏两个月份红细胞膜骨架蛋白[α-收缩蛋白(SPTA1)、β-收缩蛋白(SPTB)、带4.1蛋白(EPB4.1)]基因表达的差异(P>0.05)。结果冬季(11月份)地中海贫血患者主要血液参数Hb水平显著高于夏季(7月份)(P<0.05)。冬季(11月份)地贫患者爪甲色淡、食少纳呆、潮热盗汗的中医证候量化评分显著低于夏季(P<0.05)。冬季(11月份)红细胞抗氧化损伤指标SOD、GSH-Px活性显著低于夏季(7月份)(P<0.01),MDA的活性显著高于夏季(7月份)(P<0.01)。冬季(11月份)血清造血细胞因子SCF、EPO水平显著高于夏季(7月份)(P<0.01或P<0.05),IL-3活性水平冬季(11月份)显著低于夏季(7月份)(P<0.05)。冬季(11月份)地贫患者红细胞膜骨架蛋白SPTA1 m RNA的表达水平显著高于夏季(7月份)(P<0.05),SPTB、EPB4.1冬夏两个月份的m RNA的表达水平差异无统计学意义。结论临床研究结果进一步证实了地中海贫血患者在气温高的季节(夏季)比气温低的季节(冬季)溶血贫血严重的客观规律。实验研究显示,地中海贫血患者证候季节变化可能与冬夏两季红细胞膜骨架蛋白表达差异以及造血相关细胞因子和抗氧化损伤水平活性差异有关。但其是否为客观规律,仍需进一步的探索。

Objective To discuss the biological mechanism of symptoms seasonal variation based on erythrocyte hemolysis anemia in patients with thalassemia disease.Methods Totally 11 cases of patients with thalassemia disease were observed in the summer （ July） and winter （ November） .The levels of the quantitative score of TCM syndromes and blood parameters in the summer （ July） and winter （ No-vember） were detected respectively.The activity of the measurements of SCF,IL-3,EPO and SOD,MDA,GSH-Px were observed in the two time points.The expressions of red cell membrane skeleton protein genes were mearsured by the method of relative quantitative using RT-PCR.Results The level of blood parameters Hb in the winter（ Novermber） was significantly higher than that in the summer（ July） （P〈0.05）.The difference between two time points in RBC and Ret had no statistical significance （P〉0.05）.TCM syndrome quantita-tive score of onyx color light,eat less and anorexia,hot flushes and night sweats in the winter（Novermber）were significantly lower than those in the summer（July） （P〈0.05）.The erythrocytic SOD and GSH-Px activity were lower than the summer time point （P〈0.01） and the erythrocytic MDA activity was higher than that of the summer time point （P〈0.01）.The level of SCF and EPO activity in winter （Novermber） were significantly higher than those in summer（July） （P〈0.01, P〈0.05） and IL-3 activity level was significantly lower than that in summer（July） （P〈0.05）.The mRNA expression of the red cell membrane skeleton protein of SPTA1 in the winter （Nover-mber） was significantly higher than that in summer（July）（P〈0.05）.Conclusion Clinical research results further confirmed the objec-tive laws of symptoms seasonal variation in patients with thalassemia.Experimental studies show that symptomatic seasonal variation may be related to the differences on red cell membrane skeleton protein expression,hematopoietic cytokines activity,antioxidant injury level be-tween Winter and summer,which still need to further explore by clinical and experimental research.