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同种异体肢体移植中他克莫司的应用剂量*☆
引用本文:尚剑,刘 伟,韩昕光,凌晓东,苏俭.同种异体肢体移植中他克莫司的应用剂量*☆[J].中国神经再生研究,2011,15(31):5805-5808.
作者姓名:尚剑  刘 伟  韩昕光  凌晓东  苏俭
作者单位:哈尔滨医科大学第一附属医院骨科,黑龙江省哈尔滨市, 150001,哈尔滨医科大学第一附属医院骨科,黑龙江省哈尔滨市, 150001,哈尔滨医科大学第一附属医院骨科,黑龙江省哈尔滨市, 150001,哈尔滨医科大学第一附属医院骨科,黑龙江省哈尔滨市, 150001,哈尔滨医科大学第一附属医院骨科,黑龙江省哈尔滨市, 150001
基金项目:黑龙江教育厅科学技术研究项目(10531108)
摘    要:背景:他克莫司应用于同种异体肝移植的免疫耐受已多见报道。 目的:探索他克莫司在异体肢体移植时的最佳应用剂量。 方法:建立同种异体肢体移植大鼠模型,移植造模后设立给予不同他克莫司剂量的0.5,1,2 mg/(kg•d)组及对照组,对大鼠进行大体观察、组织学、淋巴细胞亚群测定。 结果与结论:移植后出现排斥反应的时间分别是对照组(3.43±0.79) d、0.5 mg/(kg•d)组(5.68±0.97) d、1 mg/(kg•d)组(9.13±1.17) d、2 mg/(kg•d) 组(9.61±2.38) d,排斥反应的病理分级4组分别为(2.61±0.38),(1.57±0.43),(0.85±0.24),(0.71±0.19)级。移植后各给药组CD4+、CD8+检测值均明显下降,CD4/CD8比值轻度增加或在正常值范围内;对照组CD4+、CD8+无明显变化,CD4/CD8比值明显增加。提示,他克莫司的应用剂量在1 mg/(kg•d)时就能达到理想的抑制免疫排斥反应,提高用量后意义不大。

关 键 词:他克莫司  同种异体肢体移植  造模  剂量  排斥反应

Tacrolimus application dose in limb allograft transplantation
Institution:Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China,Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China,Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China,Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China,Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Abstract:BACKGROUND: Tacrolimus (FK506) is widely used in human organ transplantation and prolongs allograft survival in several animal models, yet there is still no consistent standard in current clinical application. OBJECTIVE: To investigate the optimal application dose of FK506 in limb allograft rats. METHODS: Sixty rat models of hind limb allograft were randomly divided into three groups (A, B and C) and daily received FK506 0.5, 1, and 2 mg/kg respectively. Twenty untreated allograft rats served as the control group. Gross observation, morphological change observation and T lymphocyte subsets analysis were performed to evaluate the efficiency of FK506. RESULTS AND CONCLUSION: The occurrence time of rejection was assessed as follows: control group (3.43±0.79) days, A group (5.68±0.97) days, B group (9.13±1.17) days, and C group (9.61±2.38) days. The skin pathological grade of limb allograft rejection was grade (2.61±0.38) in the control group, grade (1.57±0.43) in the A group, grade (0.85±0.24) in the B group, and grade (0.71±0.19) in the C group. In the FK 506-treated allograft groups, the value of CD4+ and CD8+ was significantly decreased and CD4/CD8 slightly increased or kept normal condition. In the control group, CD4+ and CD8+ remained unchanged and CD4/CD8 increased significantly. FK 506 prolonged hind limb allograft survival and prevented rejection compared with untreated controls. A dose of 1 mg/kg per day could achieve the ideal effect; however, increasing the dose did not improve effect significantly.
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