Danggui Niantong Decoction ameliorates joint inflammation and cardiopulmonary injury in TNF-Tg mice

Yang Can, Chen Tao, Ma Mengjiao, Li Qiang, Liang Zhichao, Xu Hao, Wang Youhua, Li Ning, Liang Qianqian
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Abstract

Objective: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by multiple joint lesions and systemic complications. Danggui Niantong Decoction (DGNTT) has been clinically used for RA treatment; however, its beneficial effect on cardiopulmonary complications has not been reported. Methods: Female tumor necrosis factor-transgenic (TNF-Tg) mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications. Methotrexate (MTX) served as a positive control. Histopathological assessment of the joint sections was performed using hematoxylin and eosin (H&E), Alcian Blue/Orange G (ABOG), and tartrate-resistant acid phosphatase (TRAP) staining. Bone mass was assessed by micro-computed tomography (CT), inflammatory infiltrates in the heart and lungs were evaluated by H&E staining, cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining, and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin (WGA) staining. Results: DGNTT mitigated the inflammation of the ankle joint synovium, decreased the number of osteoclasts, and increased the area of cartilage and bone mass in TNF-Tg mice. In addition, DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues, accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice. As a positive control drug, MTX attenuated the pathological changes in joints, but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice. Conclusion: DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.
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当归年通汤改善TNF-Tg小鼠关节炎症和心肺损伤
目的:类风湿关节炎(RA)是一种常见的自身免疫性疾病,以多关节病变和全身并发症为特征。当归年通汤(DGNTT)临床应用于类风湿性关节炎的治疗;然而,其对心肺并发症的有益作用尚未见报道。方法:采用肿瘤坏死因子转基因(TNF-Tg)雌性小鼠,观察DGNTT对关节炎及心肺并发症的治疗作用。甲氨蝶呤(MTX)作为阳性对照。采用苏木精和伊红(H&E)、阿利新蓝/橙G (ABOG)和抗酒石酸酸性磷酸酶(TRAP)染色对关节切片进行组织病理学评估。显微计算机断层扫描(CT)评估骨量,H&E染色评估心脏和肺部炎症浸润,马松三色染色检测心肺纤维化损伤,小麦胚芽凝集素(WGA)染色检测小鼠心肌细胞肥大。结果:DGNTT能减轻TNF-Tg小鼠踝关节滑膜炎症,减少破骨细胞数量,增加软骨面积和骨量。此外,DGNTT减少了炎症细胞向肺和心脏组织的浸润,同时减少了TNF-Tg小鼠的心肺纤维化和心肌细胞肥大。作为阳性对照药物,MTX可减轻TNF-Tg小鼠关节的病理改变,但对心肺炎症和纤维化无有益作用。结论:DGNTT改善了TNF-Tg小鼠的关节病变,减轻了心肺并发症。
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