全反式维甲酸抑制IL-23/IL-17通路促进小鼠移植皮肤存活的研究

All-Trans Retinoic Acid Attenuates Interleukin-23/Interleukin-17 Pathway and Promotes Skin Allograft Survival in Mice

目的探讨全反式维甲酸(ATRA)灌胃对小鼠同种异基因皮肤移植存活时间的影响及白细胞介素(IL)-23、IL-17通路在其中的作用。方法以DBA/2小鼠为供者,Babl/c小鼠为受者建立皮肤移植模型。随机将受者分为对照组、小剂量组和大剂量组,分别在术前1 d至术后14 d或判定皮肤死亡之日每天给3组小鼠分别灌胃注射玉米油、10 mg/kg和30 mg/kg ATRA玉米油溶液。术后观察各组皮肤移植物存活时间,皮肤组织切片检测病理改变,酶联免疫吸附试验检测血清IL-23和IL-17水平,实时荧光定量PCR检测移植皮肤中IL-23、转录因子孤核受体(ROR)γt和IL-17 mRNA表达。结果与对照组比较,小剂量组和大剂量组皮肤移植存活时间延长(P<0.05),炎症细胞浸润及组织破坏程度轻,血清IL-23水平降低(P<0.05),而两治疗组间差异无统计学意义。对照组、小剂量组及大剂量组血清IL-17水平依次降低(P<0.05)。小剂量组和大剂量组皮肤移植物中IL-23、RORγt和IL-17 mRNA表达水平均较对照组低(P<0.05),而两治疗组间差异无统计学意义。结论 ATRA灌胃可显著延长小鼠移植皮肤存活时间,其机制可能与抑制IL-23、RORγt、IL-17 mRNA表达和蛋白分泌有关。

Objective To investigate the effects of all-trans retinoic acid （ATRA）-intragastric-administration on the survival time of mouse skin allografts and the role of intedeukin （IL）-23 and IL-17 thereof. Methods The skin trans- plantation of mice was done by DBA/2 as donors and Balb/c as recipients, The recipients were divided randomly into three groups： control group, low-dose group and high-dose group. Mice of the corresponding groups were intragastrically adminis- tered corn oil, 10 mg/kg ATRA and 30 mg/kg ATRA respectively from 1 day before the transplantation to the 14th day after the transplantation. The survival time of transplanted skin was observed after the operations. Skin grafts of mice were harvested for histopathological examination in three groups. The serum levels of IL-23 and IL-17 were measured by enzyme-linked im- munosorbent assay （ELISA）. The expression levels of IL-23, RORγt and IL-17 mRNA in skin allografts were detected by re- al-time fluorescent quantitative reverse transcriptase polymerase chain reaction （RT-PCR）. Results Compared with con- trol group, the average survival time of mouse skin allografts was significantly prolonged in low-dose group and high-dose group （P 〈 0.05）. The less lymphocyte infiltration and destruction of architecture were found in the skin biopsies. The serum expression of IL-23 protein was lower （P 〈 0.05）, but no significant difference was found in two treatment groups. The serum expression levels of IL- 17 protein were reduced in turn in receptors of control group, low-dose group and high-dose group （P 〈 0.05）. The expression levels of IL-23, RORγt and IL-17 mRNA in skin grafts were significantly lower in low-dose group and high-dose group than those of control group （P 〈 0.05）, but no significant difference was found in two treatment groups. Conclusion ATRA can effectively prolong the survival time of skin allografts, which may related with the inhibi- tion of the expression of IL-23, RORγt and IL-17 mRNA and the development of IL-23 and IL-17 protein.