JAK/STAT信号通路介导的免疫应答在皮瓣移植再生中的作用机制

陈盛元; 陈姣凤; 余静; 周青

JAK/STAT信号通路介导的免疫应答在皮瓣移植再生中的作用机制

Mechanism of JAK/STAT signaling pathway-mediated immune response in the regeneration of skin flap transplantation

摘要

摘要:
目的： 探究Janus激酶（JAK）/信号转导与转录激活因子（STAT）信号通路介导的免疫应答在皮瓣移植再生中的作用机制。
方法： 在SD大鼠中建立大鼠皮瓣移植模型，分为对照组与抑制剂组（于皮瓣基部局部注射JAK抑制剂AG490），检测术后第1、3、5、7天皮瓣存活率；苏木精–伊红（HE）染色评估皮瓣病理变化，Masson染色检测间质纤维化；采用实时聚合酶链反应检测术后第1、3、5、7天皮瓣组织中JAK、STAT、转化生长因子–β1（TGF–β1）、表皮细胞生长因子（EGF）、血小板衍生生长因子（PDGF）、血管内皮生长因子（VEGF）的表达水平。
结果： 术后第5、7天，抑制剂组JAK、STAT mRNA水平均显明显低于对照组（P ＜ 0.01），抑制剂组存活率均高于对照组（P ＜ 0.05和P ＜ 0.01）。HE染色半定量分析显示，术后第5天，抑制剂组炎症评分、血管评分和总评分均低于对照组（P ＜ 0.05 ~ P ＜ 0.01）；术后第7天，抑制剂组总评分明显低于对照组（P ＜ 0.01）。Masson染色半定量评分结果显示，术后第5天，抑制剂组胶原蛋白排列评分低于对照组（P ＜ 0.05）；术后第7天，抑制剂组胶原蛋白结构评分低于对照组（P ＜ 0.05）。术后第3、5、7天，抑制剂组TGF–β1、PDGF、EGF、VEGF mRNA表达水平均高于对照组（P ＜ 0.05 ~ P ＜ 0.01）。
结论： JAK抑制剂AG490可提高皮瓣存活率，可能与促进皮瓣移植血管生成、减轻炎症反应、促进生长因子的表达等相关。

Abstract:
Objective To investigate the mechanism of immune response mediated by Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway in the regeneration of skin flap transplantation.
Methods A rat skin flap transplantation model was established in SD rats. The rats were divided into a control group and an inhibitor group (JAK inhibitor AG490 was locally injected at the base of skin flap). The survival rate of skin flaps was measured on postoperative day 1, 3, 5, and day 7; hematoxylin-eosin (HE) staining was used to evaluate the pathological changes of skin flaps, and Masson staining was applied to detect interstitial fibrosis; real-time polymerase chain reaction was used to detect the expression levels of JAK, STAT, transforming growth factor-β1 (TGF-β1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) in skin flap tissue on postoperative day 1, 3, 5, and day 7.
Results On postoperative day 5 and day 7, the JAK and STAT mRNA levels in the inhibitor group were significantly lower than those in the control group (P ＜ 0.01), and the survival rate in the inhibitor group was higher than that in the control group (P ＜ 0.05 and P ＜ 0.01). HE staining semi-quantitative analysis showed that, on postoperative day 5, the inflammation score, vascular score, and total score in the inhibitor group were lower than those in the control group (P ＜ 0.05 to P ＜ 0.01); on postoperative day 7, the total score in the inhibitor group was significantly lower than that in the control group (P ＜ 0.01). Masson staining semi-quantitative analysis showed that, on postoperative day 5, the collagen arrangement score in the inhibitor group was lower than that in the control group (P ＜ 0.05); on postoperative day 7, the collagen structure score in the inhibitor group was lower than that in the control group (P ＜ 0.05). On postoperative day 3, 5, and day 7, the mRNA expression levels of TGF-β1, PDGF, EGF, and VEGF in the inhibitor group were higher than those in the control group (P ＜ 0.05 to P ＜ 0.01).
Conclusions JAK inhibitor AG490 can improve the survival rate of skin flaps, which may be associated with promoting angiogenesis in skin flap transplantation, reducing inflammatory response, and promoting expression of growth factors.

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