吸入纳米颗粒他克莫司在预防大鼠原位肺移植模型排斥反应中的疗效。

The efficacy of inhaled nanoparticle tacrolimus in preventing rejection in an orthotopic rat lung transplant model.

机构信息

Department of Cardiothoracic Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Tex.

Division of Pulmonology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Tex.

出版信息

J Thorac Cardiovasc Surg. 2017 Dec;154(6):2144-2151.e1. doi: 10.1016/j.jtcvs.2017.07.083. Epub 2017 Sep 1.

DOI:10.1016/j.jtcvs.2017.07.083

PMID:28942970

Abstract

OBJECTIVE

The immunosuppressive efficacy of inhaled nanoparticle tacrolimus was compared with systemic tacrolimus in a rodent allogeneic lung transplant model.

METHODS

Sixteen rats underwent allogeneic left orthotopic lung transplantation and were divided into 3 treatment groups: (1) inhaled nanoparticle tacrolimus: 6.4 mg tacrolimus/6.4 mg lactose twice per day; (2) intramuscular tacrolimus: 1 mg/kg tacrolimus once per day; and (3) inhaled lactose: 6.4 mg of lactose twice per day. Five days after transplant, the rats were necropsied and underwent histologic rejection grading and cytokine analysis. Trough levels of tacrolimus were measured in allograft, blood, and kidney.

RESULTS

Both intramuscular (n = 6) and nanoparticle tacrolimus (n = 6) rats displayed lower histologic grades of rejection (mean scores 3.4 ± 0.6 and 4.6 ± 0.9, respectively) when compared with lactose rats (n = 4) (mean score 11.38 ± 0.5, P = .07). Systemic tacrolimus trough levels (median) were lower in nanoparticle tacrolimus-treated rats versus intramuscular-treated rats (29.2 vs 118.6 ng/g; P < .001 in kidney, and 1.5 vs 4.8 ng/mL; P = .01 in blood).

CONCLUSIONS

Inhaled nanoparticle tacrolimus provided similar efficacy in preventing acute rejection when compared with systemic tacrolimus while maintaining lower systemic levels.

摘要

目的

比较吸入型纳米颗粒他克莫司与全身用他克莫司在啮齿动物同种异体肺移植模型中的免疫抑制效果。

方法

16 只大鼠接受同种异体左原位肺移植，并分为 3 个治疗组：（1）吸入型纳米颗粒他克莫司：每天 2 次，每次 6.4mg 他克莫司和 6.4mg 乳糖；（2）肌肉注射他克莫司：每天 1mg/kg 他克莫司；（3）吸入乳糖：每天 2 次，每次 6.4mg 乳糖。移植后 5 天，对大鼠进行尸检，并进行组织学排斥分级和细胞因子分析。测量移植物、血液和肾脏中他克莫司的谷浓度。

结果

与乳糖组（n=4）相比，肌肉注射（n=6）和纳米颗粒他克莫司组（n=6）的大鼠组织学排斥评分较低（平均评分分别为 3.4±0.6 和 4.6±0.9），差异有统计学意义（P=0.07）。与肌肉注射组相比，纳米颗粒他克莫司组大鼠的他克莫司谷浓度（中位数）在肾脏中更低（29.2 对 118.6ng/g；P<0.001），在血液中更低（1.5 对 4.8ng/mL；P=0.01）。