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胶原酶组织溶菌素对大鼠膝关节关节纤维强直模型中粘连减少的作用。

The effect of collagenase clostridium histolyticum on adhesion reduction in a rat knee arthrofibrosis model.

机构信息

Clinic of Orthopaedic and Traumatology, Çorlu State Hospital, Tekirdağ, Turkey.

Department of Orthopaedic and Traumatology, Marmara University, School of Medicine, İstanbul, Turkey.

出版信息

Acta Orthop Traumatol Turc. 2021 Sep;55(5):385-390. doi: 10.5152/j.aott.2021.20364.

DOI:10.5152/j.aott.2021.20364
PMID:34730522
Abstract

OBJECTIVE

The aim of this study was to investigate whether collagenase clostridium histolyticum (CCH) reduces intra-articular fibrotic adhesion formation in a rat model of arthrofibrosis.

METHODS

A total of 24 male Wistar rats (7 months old, weighing 220 -275 g) were randomly and equally assigned to one of two groups: the collagenase group and the control group (n = 12 each). In each group, a partial capsulotomy, and synovectomy were performed in knee. After a partial capsulotomy and synovectomy were performed in each group, the collagenase group received intra-articular CCH of 0.008 mg in 0.1 mL saline solution while the control group received the equal volume of intra-articular saline solution alone. After 6 weeks of surgery, the rats were sacrificed by decapitation, and the following outcome measures were collected. Knee range of motion (ROM) was measured using with a goniometer under 20 g force. Adhesion formation was rated using the macroscopic visual scoring system after the knee joint was exposed through a lateral parapatellar approach. Histological evaluation was performed on samples including connective tissue and fibrotic adhesions, and fibroblast cell numbers were measured performed per square. Levels of interleukin 1 (IL-1) and fibroblast growth factor (FGF) were assayed by ELISA from the intra-articular fluid.

RESULTS

The macroscopic visual scoring system was significantly lower in the collagenasegroup (median = 1, range = 0-2) than in the control group (median = 2, range = 1-3)( < 0.001).ROMwas significantly higher in the collagenase group (102° ± 12.1°) than in the control group (77° ±8.94°) (P <0.001). The number of fibroblasts obtained from the scar tissue were considerably lower in the collagenase group (mean = 16.5 ± 2.74) compared tothe control group (mean = 30.1± 4.89) (P < 0.001). Levels of IL-1 andFGF were significantly lower in the collagenase group (mean = 18.6 ng/l ± 4.39,mean = 36.3 ng/l ± 2.03; respectively) compared to the control group (mean = 31.7ng/l ± 3.75, mean = 38.7 ng/l ± 2.19; respectively) (P < 0.001).

CONCLUSION

Evidence from this study has revealed that CCH injection can inhibit the development ofarthrofibrosis, decreasing the precursor inflammatory cytokines (IL-1 and FGF-1) and histologic fibrosis in a rat knee arthrofibrosis model.

LEVEL OF EVIDENCE

Level IV, Therapeutic study.

摘要

目的

本研究旨在探讨胶原酶组织溶菌素(CCH)是否能减少关节纤维化大鼠模型中的关节内纤维粘连形成。

方法

将 24 只雄性 Wistar 大鼠(7 个月大,体重 220-275g)随机平均分为两组:胶原酶组和对照组(每组 12 只)。在每组中,进行膝关节部分囊切开术和滑膜切除术。在每组进行部分囊切开术和滑膜切除术后,胶原酶组接受 0.008mg 关节内 CCH 溶于 0.1ml 生理盐水,而对照组接受等量的关节内生理盐水。术后 6 周,通过断头法处死大鼠,收集以下结果测量值。在 20g 力的作用下,使用量角器测量膝关节活动度(ROM)。通过经外侧髌旁入路暴露膝关节后,使用宏观视觉评分系统对粘连形成进行评分。对包括结缔组织和纤维粘连在内的样本进行组织学评估,并测量每平方的成纤维细胞数量。通过酶联免疫吸附试验(ELISA)从关节液中测定白细胞介素 1(IL-1)和成纤维细胞生长因子(FGF)的水平。

结果

胶原酶组的宏观视觉评分系统明显低于对照组(中位数=1,范围=0-2)(<0.001)。胶原酶组的 ROM 明显高于对照组(102°±12.1°)(P<0.001)。胶原酶组从疤痕组织中获得的成纤维细胞数量明显低于对照组(平均值=16.5±2.74)(P<0.001)。胶原酶组的白细胞介素 1 和 FGF 水平明显低于对照组(平均值=18.6ng/l±4.39,平均值=36.3ng/l±2.03;分别)(P<0.001)。

结论

本研究结果表明,CCH 注射可抑制关节纤维化的发展,减少大鼠膝关节关节纤维化模型中前炎性细胞因子(IL-1 和 FGF-1)和组织学纤维化。

证据等级

IV 级,治疗研究。

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