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FK506 对猪肠系膜动脉的直接血管舒张作用在小肠移植中。

Direct vasodilative effect of FK506 on porcine mesenteric artery in small bowel transplantation.

机构信息

Department of Pediatric Surgery, Reproductive and Developmental Medicine, Kyushu University, Fukuoka 812-8582, Japan.

出版信息

J Pediatr Surg. 2009 Dec;44(12):2322-6. doi: 10.1016/j.jpedsurg.2009.07.060.

DOI:10.1016/j.jpedsurg.2009.07.060

PMID:20006018

Abstract

BACKGROUND

Tacrolimus (FK506) is widely used as an immunosuppressive drug in small bowel transplantation. However, its precise effects on the vascular tone of the transplanted organ have not been studied. This study aimed to clarify the effects of FK506 on the porcine mesenteric artery.

METHODS

The effects of FK506 on the changes in cytosolic Ca(2+) concentration ([Ca(2+)]i) and force using fura-2 fluorometry were investigated in mesenteric arterial strips of the porcine small intestine. The effects of FK506 on the activity of voltage-dependent Ca(2+) channels and receptor-operated Ca(2+) channels using high K(+) (118 mmol/L K(+)) depolarization and thromboxane A(2) analog (U46619) stimulation were also examined.

RESULTS

FK506 inhibited the force development induced by 118 mmol/L K(+) depolarization and 1 micromol/L U46619 stimulation in a concentration-dependent manner. The extent of inhibition of this contraction was greater than that of the K(+)-induced contraction, and its inhibitory potency was about 10-fold. FK506 (10 micromol/L) inhibited the increases in [Ca(2+)]i (24.9% +/- 7.4%) and the force development (52.0% +/- 5.6%) induced by 1 micromol/L U46619, respectively.

CONCLUSIONS

FK506 induces arterial relaxation by decreasing [Ca(2+)]i. Pretreatment of a graft with FK506 may reduce the risk of vasospasm, ischemia-reperfusion injury, and thrombosis in small bowel transplantation.

摘要

背景

他克莫司（FK506）作为一种免疫抑制剂，广泛应用于小肠移植。然而，其对移植器官血管张力的确切影响尚未得到研究。本研究旨在阐明 FK506 对猪肠系膜动脉的作用。

方法

使用 fura-2 荧光法研究 FK506 对猪小肠肠系膜动脉条带的细胞浆钙离子浓度 ([Ca(2+)]i) 和力的变化的影响。使用高钾（118mmol/L K(+)）去极化和血栓烷 A(2)类似物（U46619）刺激，研究 FK506 对电压依赖性钙通道和受体操纵钙通道活性的影响。

结果

FK506 呈浓度依赖性抑制由 118mmol/L K(+)去极化和 1µmol/L U46619 刺激引起的力的发展。这种收缩的抑制程度大于 K(+)诱导的收缩，其抑制效力约为 10 倍。FK506（10µmol/L）分别抑制 1µmol/L U46619 诱导的 [Ca(2+)]i 增加（24.9% +/- 7.4%）和力发展（52.0% +/- 5.6%）。