基于红细胞溶血贫血探讨HbH病患者症候季节变化生物学机制

Biological Mechanism of Symptoms Seasonal Variation based on Erythrocyte Hemolysis Anemia on Patients with Hemoglobin H Disease

目的:从红细胞溶血贫血探讨地中海贫血患者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)分别选取两组Hb H病患者,夏季31例,冬季35例,对两组Hb H病患者的中医证候进行量化评分;并检测两组患者血液参数水平;采用透射电镜观察两组患者红细胞膜包涵体含量的差异;检测血清造血相关细胞因子干细胞因子(SCF)、白细胞介素3(IL-3)和抗氧化损伤指标[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;对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)]基因进行相对定量。结果:冬季Hb H病患者主要血液参数Hb水平显著高于夏季组(P<0.05),Ret、Hb H冬季显著低于夏季组(P<0.05),冬夏两组Hb H病患者RBC水平差异无统计学意义(P>0.05)。冬季Hb H病患者面色萎黄、爪甲色淡、耳鸣、口咽干燥的中医证候量化评分显著低于夏季(P<0.01或P<0.05);腰膝酸软、潮热盗汗中医证候量化评分冬夏两组Hb H病患者差异无统计学意义(P>0.05)。经透射电镜可发现冬季组Hb H病患者红细胞中深色重染颗粒明显少于夏季组。见冬季组Hb H病患者红细胞SOD活性显著低于夏季组(P<0.05),两组Hb H病患者MDA和GSH-Px水平差异无统计学意义(P>0.05)。Hb H病患者红细胞膜骨架蛋白SPTA1、SPTB、EPB4.1 m RNA的表达冬季组显著高于夏季组(P<0.01)。Hb H病患者血清造血细胞因子SCF水平冬季组显著高于夏季组(P<0.05),冬夏两组Hb H病患者IL-3水平活性水平差异无统计学意义(P>0.05)。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,仍需要进一步的探索。

Objective： To discuss the biological mechanism of symptoms seasonal variation based on erythrocyte hemolysis anemia on patients with hemoglobin H disease. Methods ： Two groups patients of HbH disease were selected in the summer （ July ） and winter （ November ） .The number of summer group is 31 and the cases of winter group is 35. Detecting the levels of the quantitative score of TCM syndromes and blood parameters of two groups.Inclusion bodies in erythrocytes were detected by TEM observation.The activity of SCF, GM-CSF, IL-3 and SOD, MDA, GSH-Px were observed in the two groups.The expression of red cell membrane skeleton protein gene was mearsured by the method of relative quantitative using RT- PCR. Results ： The level of blood parameters Hb of the winter group is significantly higher than the summer group and Ret and HbH were significantly lower than summer group （ P〈0.05 ） .The difference between two groups in RBC has no statistical significance （P〉0.05）.TCM syndrome quantitative score of sallow complexion, onyx color light, tinnitus, oropharyngeal drying were significantly lower than in summer （ P〈0.01 or P〈0.05 ） .RBCs had numerous dark grains indicative of inclusion bodies formed by unmatched denatrued β-globin chains in the summer group＇s, which were more than the winter group＇s. The erythrocytic SOD activity was lower than the summer group （ P〈0.05 ） and the difference between MDA and GSH＇Px in two groups was no statistical significance （ P〉0.05 ） .The red cell membrane skeleton protein mRNA expression of the winter group is significantly higher than the summer group （ P〈0.01 ） .The SCF level in winter group was significantly higher than the summer group （P〈0.05） and IL-3 activity level is no statistical significance in the two groups （P〉0.05）. Conclusion： Clinical research results further confirmed the objective 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 between Winter and summer, which still need to further explore by clinical and experimental research.