Hepcidin-25在异体骨髓移植后并发慢性移植物抗宿主病大鼠模型和白血病患者的表达变化

Investigation of Hepcidin-25 level in rats and leukemia patients with allogeneic bone marrow transplantation complicated chronic graft versus host disease

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 Hepcidin-25 level in rats and leukemia patients with allogeneic bone marrow transplantation complicated chronic graft versus host disease （cGVHD）. Method： ①We established rat model of allogeneic bone marrow transplantation complicated cGVHD. Rats recieved irradiation alone designed as control group. The pathology change in rats were analyzed by HE staining. Hepcidin-25 mRNA levels in rats were analyzed by quantitative PCR. Hepeidin-25 in peripheral blood was determined by EI.ISA. The relationship between Hepci din-25 and liver injury were analyzed. ②Twenty-five leukemia patients with cGVHD after allogeneic bone marrow transplantation were enrolled as observation group. Another 25 leukemia patients who did not receive allogeneic bone marrow transplantation were enrolled as control group. Liver function in two groups was analyzed. Hepcidin- 25 level in peripheral blood was determined by ELISA. Result： ①The experimental model successfully established allogeneic bone marrow transplantation complicated cGVHD. Hepcidin-25 mRNA level in liver tissue in bone mar- row transplantation group was significantly higher than that in control group （P〈0.05）. Hepcidin 25 protein level in peripheral blood from bone marrow transplantation group was significantly higher than that in control group （P 〈0.05）. Hepcidin-25 level and liver injury were positively related. ②Hepcidin-25 protein level and alanine amin- otransferase in leukemia patients with bone marrow transplantation complicated cGVHD in peripheral blood was significantly higher than those in patients who did not receive bone marrow transplantation （P〈0.05）. Conclusion.. Hepcidin-25 mRNA and protein level in rats with allogeneic bone marrow transplantation complicated cGVHD are significantly increased. Hepcidin-25 is closely related to liver damage. This result is furtherly confirmed in clinical samples. It suggests that Hepcidin-25 levels can be used as a clinical diagnostic marker of bone marrow transplan tation complicated cGVHD in leukemia patients.