脂质体包裹羟基喜树碱在预防新西兰白兔硬膜外瘢痕形成中的应用。

Application of liposome-encapsulated hydroxycamptothecin in the prevention of epidural scar formation in New Zealand white rabbits.

机构信息

Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Rd, Huangpu District, Shanghai 200003, People's Republic of China.

出版信息

Spine J. 2011 Mar;11(3):218-23. doi: 10.1016/j.spinee.2011.01.028.

DOI:10.1016/j.spinee.2011.01.028

PMID:21377604

Abstract

BACKGROUND CONTEXT

Epidural adhesion and fibrosis attribute to the prevalence of pain in normal wound healing after laminectomy surgery. Hydroxycamptothecin (HCPT), an antitumor drug, has proved to be effective in preventing fibroblast proliferation and reducing epidural adhesion after laminectomy in vivo animal study. However, HCPT's disadvantages, such as poor solubility and short half-life, limit its application clinically. Compared with HCPT, the liposome-encapsulated HCPT (L-HCPT) could reduce epidural fibrosis by preventing the proliferation of fibroblast in the scar tissues with longer half-life and increased solubility.

PURPOSE

To evaluate the suitability of L-HCPT in the laminectomy models on rabbits and to explore the mechanisms in the prevention of epidural scar formation.

STUDY DESIGN

An original investigation that characterizes the novel delivery system in the combinational application of HCPT and liposome (L-HCPT).

PATIENT SAMPLE

The sample comprises 24 mature New Zealand white adult rabbits.

METHODS

Lumbar laminectomies at L4 and L6 with an L5 disc injury were performed on 24 mature New Zealand white adult rabbits. The rabbits were then randomized into three groups. In Group I, the laminectomy site was treated with a cotton pad soaked with HCPT solution (1 mg/mL) for 5 minutes (HCPT group) and was flushed with saline completely. In Group II, 1 mL of L-HCPT was seeded on the laminectomy area (L-HCPT group). In Group III, the laminectomy area was flushed with saline before wound closure (control group). After 28 days, the animals underwent magnetic resonance imaging. The animals were euthanized; the spinal section was removed for macroscopic evaluation, and hydroxyproline in the scar tissue was quantified.

RESULTS

Operation in all the animals yielded a reproducible laminectomy, without complication or mortality. In the laminectomy sites treated with L-HCPT, the dura mater was clean without any evident adhesion. Magnetic resonance imaging analysis implied that L-HCPT treatment could reduce the epidural scar significantly compared with saline control group, which was further proved by the decreased concentration of hydroxyproline in the scar tissues.

CONCLUSION

These results demonstrate that the treatment of postlaminectomy wounds in rabbits with L-HCPT reduces the severity of adhesion.

摘要

背景

硬膜外粘连和纤维化是导致脊柱手术后正常伤口愈合疼痛的主要原因。羟基喜树碱（HCPT）是一种抗肿瘤药物，已被证明在体内动物研究中可有效预防纤维母细胞增殖和减少椎板切除术后硬膜外粘连。然而，HCPT 的缺点，如溶解度差和半衰期短，限制了其在临床上的应用。与 HCPT 相比，脂质体包封的 HCPT（L-HCPT）可以通过防止瘢痕组织中纤维母细胞的增殖来减少硬膜外纤维化，从而具有更长的半衰期和更高的溶解度。

目的

评估 L-HCPT 在兔椎板切除模型中的适用性，并探讨其在预防硬膜外瘢痕形成中的机制。

研究设计

这是一项原创性研究，对 HCPT 与脂质体联合应用的新型给药系统进行了特征描述。

患者样本

该样本包含 24 只成熟的新西兰大白兔成年兔。

方法

对 24 只成熟的新西兰大白兔成年兔进行 L4 和 L6 腰椎椎板切除术，同时损伤 L5 椎间盘。然后，将这些兔子随机分为三组。在第 I 组中，用浸有 HCPT 溶液（1mg/mL）的棉垫处理椎板切除术部位 5 分钟（HCPT 组），并用生理盐水完全冲洗。在第 II 组中，将 1ml 的 L-HCPT 接种于椎板切除术区域（L-HCPT 组）。在第 III 组中，在伤口闭合前用生理盐水冲洗椎板切除术区域（对照组）。28 天后，对动物进行磁共振成像检查。处死动物，取出脊髓段进行大体评估，并定量分析瘢痕组织中的羟脯氨酸。