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他克莫司在预防大鼠椎板切除术后硬膜外瘢痕粘连中的免疫调节作用。

Immunomodulatory effectiveness of tacrolimus in preventing epidural scar adhesion after laminectomy in rat model.

机构信息

Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.

出版信息

Eur J Pharmacol. 2013 Jan 15;699(1-3):194-9. doi: 10.1016/j.ejphar.2012.11.037. Epub 2012 Dec 3.

Abstract

There was no previous study about topical application of tacrolimus (FK506) could inhibit fibroblast proliferation and prevent epidural scar adhesion after laminectomy. We intended to illustrate the effect of FK506 on inhibiting fibroblast proliferation and preventing epidural scar adhesion after laminectomy in rat model. In our study, seventy-two rats were randomly divided into four groups (0.1mg/ml group, 0.05 mg/ml group, 0.01 mg/ml group and control group). Laminectomy was performed at Lumbar-1 level, and then different concentrations of FK506 and saline were applied to the laminectomy sites. Four weeks later the rats were killed and the epidural adhesion was evaluated. Macroscopic assessment, hydroxyproline content analysis, histological analysis and mRNA measurements were used to evaluate the effect of FK506 on reducing epidural scar adhesion. The results showed that FK506 could prevent epidural scar adhesion in a dose-dependent manner. Little epidural adhesions were seen in the laminectomy sites treated with 0.1mg/ml FK506. The hydroxyproline content, the number of fibroblasts, the mRNA expression level of IL-2 and TGF-β1 in 0.1mg/ml FK506 group were significantly less than those of 0.05 mg/ml FK506 group, 0.01 mg/ml FK506 group and control group. However, dense epidural adhesions were found in 0.01 mg/ml FK506 group and control group. The hydroxyproline content and the number of fibroblasts in 0.01 mg/ml group showed no significant difference compared with those of control group. In conclusion, topical application of 0.1mg/ml FK506 could inhibit fibroblast proliferation and prevent epidural scar adhesion after laminectomy in rat model.

摘要

先前没有研究表明他克莫司(FK506)的局部应用可以抑制纤维母细胞增殖并防止椎板切除术后硬膜外瘢痕粘连。我们旨在说明 FK506 对抑制纤维母细胞增殖和防止椎板切除术后硬膜外瘢痕粘连的作用。在我们的研究中,72 只大鼠随机分为四组(0.1mg/ml 组、0.05mg/ml 组、0.01mg/ml 组和对照组)。在腰椎 1 水平进行椎板切除术,然后将不同浓度的 FK506 和生理盐水应用于椎板切除部位。四周后处死大鼠,评估硬膜外粘连程度。采用大体评估、羟脯氨酸含量分析、组织学分析和 mRNA 测量来评估 FK506 减少硬膜外瘢痕粘连的效果。结果表明,FK506 可以以剂量依赖的方式预防硬膜外瘢痕粘连。在 0.1mg/ml FK506 处理的椎板切除部位几乎没有硬膜外粘连。0.1mg/ml FK506 组羟脯氨酸含量、纤维母细胞数量、IL-2 和 TGF-β1 的 mRNA 表达水平明显低于 0.05mg/ml FK506 组、0.01mg/ml FK506 组和对照组。然而,在 0.01mg/ml FK506 组和对照组中发现了致密的硬膜外粘连。0.01mg/ml 组羟脯氨酸含量和纤维母细胞数量与对照组相比无显著差异。总之,0.1mg/ml FK506 的局部应用可以抑制纤维母细胞增殖并防止大鼠椎板切除术后硬膜外瘢痕粘连。

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