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芹菜素通过 TGFβ/SMADs 信号通路抑制急性脊髓损伤后的纤维瘢痕形成。

Apigenin inhibits fibrous scar formation after acute spinal cord injury through TGFβ/SMADs signaling pathway.

机构信息

Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Tianjin Medical University, Tianjin, China.

出版信息

CNS Neurosci Ther. 2022 Nov;28(11):1883-1894. doi: 10.1111/cns.13929. Epub 2022 Jul 30.

DOI:10.1111/cns.13929
PMID:35906830
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9532920/
Abstract

AIM

To investigate the effect of apigenin on fibrous scar formation after mouse spinal cord injury (SCI).

METHODS

The pneumatic impactor strike method was used to establish an SCI model. Mice were intraperitoneally injected with 5 mg/kg or 20 mg/kg apigenin daily for 28 days after SCI. The Basso Mouse Scale (BMS) score, hematoxylin-eosin staining, and immunohistochemical staining were used to assess the effect of apigenin on scar formation and motor function recovery. Western blotting and qRT-PCR were used to detect the expression of fibrosis-related parameters in spinal cord tissue homogenates. NIH-3 T3 cells and mouse primary spinal cord fibroblasts, α-Smooth muscle actin (α-SMA), collagen 1, and fibronectin were used to evaluate apigenin's effect in vitro. Western blotting and immunofluorescence techniques were used to study the effect of apigenin on TGFβ/SMADs signaling.

RESULTS

Apigenin inhibited fibrous scar formation in the mouse spinal cord and promoted the recovery of motor function. It reduced the expression of fibroblast-related parameters and increased the content of nerve growth factor in vivo, decreasing myofibroblast activation and collagen fiber formation by inhibiting TGFβ-induced SMAD2/3 phosphorylation and nuclear translocation in vitro.

CONCLUSION

Apigenin inhibits fibrous scar formation after SCI by decreasing fibrosis-related factor expression through TGFβ/SMADs signaling.

摘要

目的

研究芹菜素对小鼠脊髓损伤后纤维瘢痕形成的影响。

方法

采用气动冲击器打击法建立脊髓损伤模型。脊髓损伤后,小鼠每日腹腔内注射 5mg/kg 或 20mg/kg 芹菜素,共 28 天。用 Basso 小鼠步态评分、苏木精-伊红染色和免疫组织化学染色评估芹菜素对瘢痕形成和运动功能恢复的影响。Western blot 和 qRT-PCR 检测脊髓组织匀浆中纤维化相关参数的表达。用 NIH-3T3 细胞和小鼠原代脊髓成纤维细胞、α-平滑肌肌动蛋白(α-SMA)、胶原蛋白 1 和纤维连接蛋白评估芹菜素的体外作用。Western blot 和免疫荧光技术研究芹菜素对 TGFβ/SMADs 信号通路的影响。

结果

芹菜素抑制了小鼠脊髓中的纤维瘢痕形成,促进了运动功能的恢复。它降低了成纤维细胞相关参数的表达,并增加了体内神经生长因子的含量,通过抑制 TGFβ 诱导的 SMAD2/3 磷酸化和核转位,减少了肌成纤维细胞的激活和胶原纤维的形成。

结论

芹菜素通过 TGFβ/SMADs 信号通路降低纤维化相关因子的表达,抑制脊髓损伤后纤维瘢痕的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/38db7b8b4742/CNS-28-1883-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/dfbb3734d099/CNS-28-1883-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/fe227352658d/CNS-28-1883-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/5115425c0714/CNS-28-1883-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/5f9edfd5f8c8/CNS-28-1883-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/9cbb10e02111/CNS-28-1883-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/38db7b8b4742/CNS-28-1883-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/dfbb3734d099/CNS-28-1883-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/fe227352658d/CNS-28-1883-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/5115425c0714/CNS-28-1883-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/5f9edfd5f8c8/CNS-28-1883-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/9cbb10e02111/CNS-28-1883-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdc/9532920/38db7b8b4742/CNS-28-1883-g002.jpg

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