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目的:探讨Hepcidin-25在异体骨髓移植后并发慢性移植物抗宿主病(cGVHD)大鼠模型和白血病患者机体中mRNA和蛋白质水平变化及临床意义。方法:1建立异体骨髓移植并发cGVHD大鼠模型,以单纯射线照射大鼠作为对照组,采用HE染色分析2组大鼠肝脏病理学变化,采用荧光定量PCR分析肝脏组织中Hepcidin-25mRNA水平,采用ELISA法检测外周血中Hepcidin-25的表达水平,并分析肝组织中Hepcidin-25水平与肝脏病理学关系。2选取25例异体骨髓移植后并发cGVHD白血病患者作为研究对象,同时选取来我院就诊的25例未接受骨髓移植的白血病患者作为对照研究。分析2组患者肝功能,并采用ELISA法分析对照组和观察组外周血中Hepcidin-25的水平。结果:1本实验成功建立异体骨髓移植并发cGVHD大鼠模型。骨髓移植组大鼠肝组织中Hepcidin-25mRNA水平明显高于对照组(P<0.05),骨髓移植组大鼠外周血中Hepcidin-25蛋白水平亦明显高于对照组(P<0.05)。肝脏组织中Hepcidin-25mRNA水平与肝损伤呈正相关。2骨髓移植后并发cGVHD白血病患者外周血中Hepcidin-25蛋白水平和谷丙转氨酶均明显高于未接受骨髓移植白血病患者(均P<0.05)。Hepcidin-25水平与谷丙转氨酶水平变化呈正相关。结论:异体骨髓移植并发cGVHD大鼠肝脏和外周血中Hepcidin-25mRNA和蛋白水平均显著增加,且与靶器官肝脏损伤密切相关。这一结果在临床样本中得到了进一步证实,提示Hepcidin-25水平可作为临床骨髓移植并发cGVHD白血病患者的诊断标志。
Objective: To investigate the changes and clinical significance of Hepcidin-25 mRNA and protein levels in chronic graft-versus-host disease (cGVHD) rat models and leukemia patients after allogeneic bone marrow transplantation. METHODS:1 Allogeneic bone marrow transplantation complicated with cGVHD rat model was established. Rats were irradiated with simple radiation as the control group. HE pathological changes of the rats in the two groups were analyzed by HE staining. The level of Hepcidin-25 mRNA in liver tissues was analyzed by fluorescence quantitative PCR. The expression of Hepcidin-25 in peripheral blood was detected by ELISA, and the relationship between Hepcidin-25 level in liver tissue and liver pathology was analyzed. 2 Twenty-five patients with cGVHD leukemia complicated with allogeneic bone marrow transplantation were selected as the study subjects. Twenty-five patients with leukemia without bone marrow transplantation who came to our hospital were selected as controls. Liver function of the two groups was analyzed, and levels of Hepcidin-25 in the peripheral blood of the control group and the observation group were analyzed by ELISA. Results: 1 This experiment successfully established allogeneic bone marrow transplantation with cGVHD rat model. The level of Hepcidin-25 mRNA in the liver tissue of the bone marrow transplantation group was significantly higher than that of the control group (P<0.05). The level of Hepcidin-25 protein in the peripheral blood of the bone marrow transplantation group was also significantly higher than that of the control group (P<0.05). Hepcidin-25 mRNA levels were positively correlated with liver injury in liver tissue. 2 The levels of Hepcidin-25 protein and alanine aminotransferase in peripheral blood of patients with cGVHD leukemia complicated with bone marrow transplantation were significantly higher than those without bone marrow transplantation (P<0.05). Hepcidin-25 levels were positively correlated with changes in alanine aminotransferase levels. CONCLUSION: Hepcidin-25 mRNA and protein levels in liver and peripheral blood of cGVHD rats were significantly increased after allogeneic bone marrow transplantation, and were closely related to target organ liver injury. This result was further confirmed in clinical samples, suggesting that Hepcidin-25 level can be used as a diagnostic marker for patients with clinical bone marrow transplantation complicated by cGVHD leukemia.