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核心蛋白聚糖通过抑制TGF-β1/SMAD和MAPK信号通路抑制微波消融后硬结的形成:巴马小型猪乳腺增生模型研究

Decorin inhibits the formation of hard nodules after microwave ablation by inhibiting the TGF-β1/SMAD and MAPK signaling pathways: in a Bama miniature pig model of mammary gland hyperplasia.

作者信息

Du Yue, Liu Xinyao, Du Kai, Zhang Wenkai, Li Rui, Yang Lizhi, Cheng Linggang, He Wen, Zhang Wei

机构信息

Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Int J Hyperthermia. 2023;40(1):2188151. doi: 10.1080/02656736.2023.2188151.

DOI:10.1080/02656736.2023.2188151
PMID:36919520
Abstract

BACKGROUND

Benign breast lesions are often associated with hard nodule formation after microwave ablation (MWA), which persists for a long time and causes problems in patients. The aim of this study was to evaluate the efficacy of decorin in the treatment of hard nodule formation and its potential mechanism of action.

METHODS

Using a Bama miniature pig model of mammary gland hyperplasia, immunohistochemistry, Masson's trichrome and western blotting were firstly applied to compare the extent of fibrosis and activation of key members of the TGF-β1/SMAD and MAPK signaling pathways of hard nodule in the control and MWA groups, and then the extent of fibrosis and expression of signaling pathways in hard nodule were examined after application of decorin.

RESULTS

The results showed that the MWA group had increased levels of TGF-β1, p-SMAD2/3, p-ERK1/2, and collagen I proteins and increased fibrosis at 2 weeks, 4 weeks, and 3 months after MWA. After decorin treatment, the expression levels of each protein were significantly downregulated, and the degree of fibrosis was reduced at 2 weeks, 4 weeks, and 3 months after MWA compared with the MWA group.

CONCLUSION

In conclusion, these results suggest that activation of TGF-β1 may play an important role in hard nodule formation and that decorin may reduce hard nodule formation after MWA in a model of mammary gland hyperplasia by inhibiting the TGF-β1/SMAD and MAPK signaling pathways.

摘要

背景

良性乳腺病变在微波消融(MWA)后常伴有硬结形成,且持续时间较长,给患者带来困扰。本研究旨在评估核心蛋白聚糖在治疗硬结形成中的疗效及其潜在作用机制。

方法

采用巴马小型猪乳腺增生模型,首先应用免疫组织化学、Masson三色染色和蛋白质印迹法比较对照组和MWA组硬结中TGF-β1/SMAD和MAPK信号通路关键成员的纤维化程度和激活情况,然后在应用核心蛋白聚糖后检测硬结中纤维化程度和信号通路的表达。

结果

结果显示,MWA组在MWA后2周、4周和3个月时,TGF-β1、p-SMAD2/3、p-ERK1/2和I型胶原蛋白水平升高,纤维化增加。核心蛋白聚糖治疗后,与MWA组相比,MWA后2周、4周和3个月时各蛋白表达水平显著下调,纤维化程度降低。

结论

总之,这些结果表明TGF-β1的激活可能在硬结形成中起重要作用,并且核心蛋白聚糖可能通过抑制TGF-β1/SMAD和MAPK信号通路,在乳腺增生模型中减少MWA后的硬结形成。

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