大鼠自体内瘘模型制备及内瘘狭窄的实验研究

A rat model of autogenous internal arteriovenous fistula and the experimental study on internal fistula stenosis

目的吻合口内膜增生可导致自体动静脉内瘘失功,本研究拟在设计大鼠模型研究其进程及机制。方法SPF 级wistar 大鼠,行右颈总动脉-颈内静脉端端吻合,术后14,28 天处死,取近吻合口静脉、动脉组织,行 HE 染色,弹力、胶原纤维的双重组合染色,PCNA、TGF- β 1、NF- κ B 免疫组化。结果内瘘吻合术后 14 天近吻合口静脉端见明显的内膜增生,呈息肉样增生,其中平滑肌细胞增生活跃,大量胶原纤维沉积,28 天管腔明显狭窄。特殊染色见术后 14、28 天近吻合口静脉内弹力层不连续。PCNA、NF- κB在近吻合口静脉壁中膜和外膜高表达,在14 天达到一个高峰,在28 天观察期内仍持续高表达。TGF- β1 在外膜基质高表达。结论大鼠右侧颈总动脉-颈内静脉端端吻合可模拟内瘘局部血流动力学的影响,短期内可见明显内膜增生等病理表现,是一种合适的自体动静脉内瘘动物模型,显示TGF- β1,NF- κB参与了内瘘内膜增生病理过程。

Objective Intimal hypcrplasia at the anastomosis site may cause the failure of autogenous artcriovenous fistula. We designed a rat model to study this process and its mechanism. Methods Wistar rats were subjected to end-to-end anastomosis of the right carotid artery and internal jugular vein. After the operation for 14 and 28 days, rats were sacrificed, and the artery and vein near the anastomosis site were examined for histological changes after staining with HE, combined staining for elastic and collagen fibers, and immunohistochemical staining for PCNA, TGF-β1 and NF-kB. Results After the operation for 14 days, apparent intimal hyperplasia was found at the venous end near the anastomosis site, appearing as polypoid hyperplasia. Vascular smooth muscle cells proliferated with the prominent deposition of collagen fibers. After the operation for 28 days, stenosis of the lumen occurred. The inner elastic layer discontinued at the anastomosis site even after the operation for 28 days. PCNA and NF-kB were highly expressed in medial and adventitial layers of the vein near the anastomosis site after the operation for 14 days and remained highly expressed after 28 days. TGF-β1 was highly expressed in the matrix of adventitial layer. Conclusion This rat model can mimic the local hemodynamic changes in internal fistula. Apparent intimal hyperplasin was seen in this model within 28 days, being useful as an autogenous arteriovenous fistula model. We also found that TGF-β1 and NF-kB were involved in the pathological processes of intimal proliferation in internal fistula.