FK506 induces the atrophy of enteric ganglia in small bowel transplantation, which can be prevented by the neuropeptide bombesin

FK506 induces the atrophy of enteric ganglia in small bowel transplantation, which can be prevented by the neuropeptide bombesin
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DOI:
10.1016/j.transproceed.2006.05.010
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发表时间:
2006-07-01
影响因子:
0.9
通讯作者:
Iwai, N.
Iwai, N.
中科院分区:
医学4区
文献类型:
--
作者:
Higuchi, K.;Kimura, O.;Iwai, N.

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目的.广泛用于免疫抑制的FK 506据报道具有神经毒性。然而,其对移植肠神经节(TGEG)的神经毒性尚未见报道。本研究的目的是研究FK 506是否对TGEG具有神经毒性作用,以及蛙皮素(BBS)是否可以防止这种萎缩。采用袖套法将18只接受联合异位小肠移植(SBTx)的大鼠分为3组,每组6只; A:单独SBTx,B:SBTx + FK 506,C:SBTx + FK 506/BBS。从第14天至第28天连续输注BBS(10 mg/kg/d)或生理盐水。B组和C组大鼠每日肌肉注射FK 506(0.32 mg/kg/d)。采用蛋白基因产物(PGP)9.5免疫组化进行TGEG分析。通过计算每个移植物中PGP9.5阳性神经节的数量来获得神经节的数量。与A组(69.7 ± 6.0 G/CS)相比,B组(51.5 ± 7.7 G/CS)的TGEG数目明显减少,而C组(84.8 ± 10.2 G/CS)的TGEG数目保存良好。B组与C组比较有显著性差异(P
Purpose. FK506, which is widely used for immunosuppression, is reported to have neurotoxicity. However, its neurotoxicity for transplanted graft enteric ganglia (TGEG) has never been reported. The aim of this study was to investigate whether FK506 has a neurotoxic effect on TGEG, and whether bombesin (BBS) prevents such atrophy.Methods. Eighteen rats that underwent syngertic heterotopic small bowel transplantation (SBTx) using a cuff method were divided into three groups of six rats each; A: SBTx alone, B: SBTx with FK506, C: SBTx with FK506/BBS. Either BBS (10 mg/kg/d) or normal saline was infused continuously from day 14 to 28. Rats in groups B and C were administered FK506 (0.32 mg/kg/day, intramuscularly) daily. Analysis of TGEG was performed using immunohistochemistry with protein gene product (PGP) 9.5. The ganglionic number was obtained by counting PGP9.5-positive ganglia in each graft.Results. The number of TGEG were reduced significantly in group B (51.5 +/- 7.7 ganglia per cross section (G/CS)) compared with group A (69.7 +/- 6.0 G/CS), but were well preserved in group C (84.8 +/- 10.2 G/CS). There were significant differences between groups B and C (P