周围神经损伤后再生速度很缓慢，一直是困扰临床的难题。FK506通过免疫抑制和神经营养促进周围神经再生的作用已被国内外多项研究证实。我们前期研究首次发现FK506还能通过诱导成纤维细胞凋亡来减少神经吻合口瘢痕形成而促进周围神经再生。但FK506诱导成纤维细胞凋亡的确切分子机制及其对瘢痕形成过程中细胞外基质的影响尚不十分清楚。本课题拟采用大鼠神经吻合口瘢痕模型，通过检测内质网应激关键分子CHOP、Caspase-12、JNK以及细胞外基质COL-1，3、MMPs、LH2b等表达的变化，观察内质网应激在FK506诱导神经吻合口瘢痕成纤维细胞凋亡和细胞外基质表达中的作用。并采用siRNA技术抑制CHOP和Caspase-12的表达，从正反两方面阐明FK506诱导成纤维细胞经内质网应激途径凋亡的确切信号通路，更深入揭示FK506减少神经吻合口瘢痕形成的机制，为促进周围神经再生提供新的方法和研究思路。

The neural regeneration and functional recovery after peripheral nerve injury are very slow, which has been a tough problem in clinical medicine. It has been demonstrated by many investigations that FK506 could promote nerve regeneration through its immune inhibition and neurotrophic activity. Our previous study primarily found that FK506 could promote peripheral nerve regeneration through inducing fibroblast apoptosis and reducing scar formation in nerve anastomosis. But the exact molecular mechanisms by which FK506 induces fibroblast apoptosis and the influence of FK506 on extracellular matrix in the process of scar formation remain unclear. Through establishing nerve anastomosis scar in rat model and detecting the expression levels of endoplasmic reticulum stress (ERS) related molecules (CHOP, Caspase-12 and JNK) and extracellular matrix (COL-1, COL-3, MMPs and LH2b et al), this study is to explore the effect of ERS on fibroblast apoptosis and extracellular matrix expression induced by FK506. Also, we will investigate the influence of CHOP siRNA and Caspase-12 siRNA on fibroblast apoptosis and extracellular matrix expression induced by FK506. Thus, through the research above-mentioned, we can elucidate the exact cell signaling of ERS by which FK506 induces fibroblast apoptosis and further reveal the mechanisms by which FK506 reduces scar formation in nerve anastomosis. Moreover, this study will provid new methods and ideas for promoting peripheral nerve regeneration.