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沙丁胺醇治疗子宫内膜异位症小鼠模型的疗效研究。

Investigation of the Therapeutic Effect of Salbutamol on Endometriosis in a Mouse Model.

机构信息

Department of Gynaecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.

Department of Gynaecology, Zhejiang Xiaoshan Hospital, Hangzhou, Zhejiang, PR China.

出版信息

Reprod Sci. 2024 Feb;31(2):430-440. doi: 10.1007/s43032-023-01371-0. Epub 2023 Oct 9.

Abstract

Endometriosis is an immune chronic inflammatory disease, and there are currently no more effective drugs for treating endometriosis due to its unknown etiology. Salbutamol is a β2-adrenergic receptor (β2AR) agonist commonly used to treat asthma by selectively activating β2 receptors on airway smooth muscle and leukocytes, exerting bronchial dilation and synergistic anti-inflammatory effects. In recent years, β2AR agonists have been used in endometriosis studies, and we speculate that salbutamol may have a therapeutic effect on endometriosis. The purpose of this research was to explore the therapeutic effect of salbutamol on endometriosis mice. The mouse endometriosis model was established and treated with different doses of salbutamol. Endometrial lesions were harvested for pathological diagnosis, immunohistochemistry (IHC), Masson staining, and toluidine blue analysis. We found that the number and size of endometriotic lesions were all significantly decreased after 3 weeks of treatment with different doses of salbutamol on endometriosis model mice (P < 0.05). After Salbutamol treatment, the amount of mast cells (toluidine blue) and macrophages (F4/80) in the lesions as well as the expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-ɑ, platelet-derived growth factor subunit B (PDGFB), CD31, transforming growth factor (TGF)-β, Masson staining, BCL2, TUBB3, substance P (SP), and nerve growth factor (NGF) were significantly reduced (P < 0.05). These results suggested that salbutamol could effectively treat endometriosis in mice by reducing immune inflammatory cells and factors, angiogenesis, and fibrosis, increasing apoptosis of endometriotic lesions, and decreasing neurogenesis.

摘要

子宫内膜异位症是一种免疫慢性炎症性疾病,由于其病因不明,目前尚无更有效的治疗子宫内膜异位症的药物。沙丁胺醇是一种β2-肾上腺素能受体(β2AR)激动剂,通常通过选择性激活气道平滑肌和白细胞上的β2 受体来治疗哮喘,发挥支气管扩张和协同抗炎作用。近年来,β2AR 激动剂已被用于子宫内膜异位症的研究,我们推测沙丁胺醇可能对子宫内膜异位症有治疗作用。本研究旨在探讨沙丁胺醇对子宫内膜异位症小鼠的治疗作用。建立了小鼠子宫内膜异位症模型,并给予不同剂量的沙丁胺醇进行治疗。采集子宫内膜病变进行病理诊断、免疫组织化学(IHC)、Masson 染色和甲苯胺蓝分析。我们发现,在子宫内膜异位症模型小鼠中,不同剂量的沙丁胺醇治疗 3 周后,子宫内膜异位症病变的数量和大小均明显减少(P<0.05)。沙丁胺醇治疗后,病变中肥大细胞(甲苯胺蓝)和巨噬细胞(F4/80)的数量以及白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-ɑ、血小板衍生生长因子亚基 B(PDGFB)、CD31、转化生长因子(TGF)-β、Masson 染色、BCL2、TUBB3、P 物质(SP)和神经生长因子(NGF)的表达均显著降低(P<0.05)。这些结果表明,沙丁胺醇通过减少免疫炎性细胞和因子、血管生成和纤维化,增加子宫内膜异位症病变的细胞凋亡,减少神经发生,可有效治疗小鼠子宫内膜异位症。

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