The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repai...The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue.In this study,the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No.10-0 suture.The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks.Compared with the control group（stoma wrapped with gelfoam soaked with physiological saline）,the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo,suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons.These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.展开更多
In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Gro...In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.展开更多
基金supported by the Natural Science Foundation of Hubei Province of China,No.2011CDB392
文摘The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue.In this study,the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No.10-0 suture.The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks.Compared with the control group（stoma wrapped with gelfoam soaked with physiological saline）,the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo,suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons.These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.
文摘In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.
