地贫并脾亢脾切除后内脏铁沉积变化的动物实验及临床MRI研究

Thalassemia major causes complications such as anemia， iron overload in myocardium, liver, spleen and pancreas, ehypersplenism，etc. As one of the treatment of ehypersplenism，splenectomy can reduce the destruction of red blood cells, and then reduce the amount of blood transfusion. However, as an major organ of iron deposition, following splenectomy, total body iron storage capacity is reduced, the iron concentration in other organs， such as liver, myocardium maybe increase. While heart failure due to myocardial iron deposition is the major cause of death in thalassemia major. Recent literatures shows, after splenectomy, serum ferritin concentration increased, implying that visceral iron concentration will increase. Our previous study demonstrated that in patients with thalassemia, liver / muscle signal intensity ratios in splenectomy group are less than the non-splenectomy group, which，suggesting that splenectomy increased hepatic iron concentration. So, What is the variation about body iron deposition in organs such as liver, myocardium, pancreas, etc, after splenectomy? How to quantify the clinical diagnosis? There are still lots of problems. In this study, through the establishment of a parallel model of pig with iron overload, qualitative and quantitative measurements iron concentration using MRI before and after splenectomy; Qualitative and quantitative studies the variation of visceral iron concentration using MRI, before and after splenectomy in patients with thalassemia. In order to investigate the changes of iron overload after splenectomy, and to provide a theoretical foundation for thalassemia treatment plan.

重型地中海贫血主要造成贫血、心、肝、脾、胰腺等内脏铁沉积以及脾亢等并发症。做为脾亢治疗手段之一，脾切除术可以减少红细胞破坏，减少输血量。然而，作为铁沉积的重要器官，脾切除术后，内脏铁沉积的容量器官减少，可能会加重心、肝等脏器的铁沉积，而心肌铁沉积所致心衰是地贫的重要死亡原因。近期文献报道，地贫脾切除术后，血清铁蛋白浓度增加，提示内脏铁沉积会加重。我们前期的研究表明，重型地贫患者中，脾切除组的肝脏/肌肉信号强度比小于非脾切除组，提示脾切除后，加重了肝铁沉积。所以，脾切除后，体内铁在肝、心、胰腺等器官沉积有什么变化规律，临床如何进行定量诊断还存在很多问题。本研究将通过建立猪的铁沉积模型并行脾切除前后铁的定性、定量MRI 研究，以及对地贫患者脾切除前后内脏铁浓度的MRI定性、定量追踪研究，探讨脾切除术后内脏铁沉积的变化规律，为地贫治疗方案的制定提供理论依据。

重型地中海贫血主要造成贫血、心、肝、脾、胰腺等内脏铁沉积以及脾亢等并发症。做为脾亢治疗手段之一，脾切除术可以减少红细胞破坏，减少输血量。然而，作为铁沉积的重要器官，脾切除术后，内脏铁沉积的容量器官减少，可能会加重心、肝等脏器的铁沉积，而心肌铁沉积所致心衰是地贫的重要死亡原因。本课题通过建立猪的铁沉积模型30头，并将实验猪分为3组：脾切除铁剂未减量组、脾切除铁剂减量组、非脾切除组，并继续注射铁剂并行MRI 检查，测量心肌、肝脏R2*，评价脾脏切除手术对实验猪铁沉积的影响。在年龄、地中海贫血基因类型、输血量、祛铁治疗方案及时间配对的情况下，选取脾脏切除地中海贫血病例55例，非脾脏切除地中海贫血病例55例，对两组病人行MRI 检查，测量心肌、肝脏R2*，探讨脾切除手术对内脏铁沉积的影响。动物实验显示：脾切除术后，在注射铁剂不减量的情况下，脾切组的肝脏铁浓度高于非脾切除组。脾切除术后，在注射铁剂减量的至70%的情况下，脾切组的肝脏铁浓度低于非脾切除组。由于实验猪心肌铁沉积较少，脾切除组、脾切除并铁剂减量组、非脾切除组心肌铁沉积差异没有统计学意义。临床数据显示：脾切除组（55例）的肝脏铁沉积较非脾切除组(55例）明显。脾切除组与非脾切除组心肌铁沉积差别没有统计学意义，原因可能为统计病例相对不足以及由于病人服用祛铁药物，心肌铁沉积不明显，而且脾切除组的心肌R2*大于非脾切除组，P值接近0.05，如果加大病人量，差别可能会有统计学意义。综上所述，脾脏切除手术可以增加地中海贫血病人其它脏器的铁沉积，临床在治疗地中海贫血病人时，需要慎重考虑脾脏切除手术。