Zhongguo quanke yixue (Aug 2024)
Efficacy of Zang Bi Formula in Treating Arthritis and Its Pulmonary Complications in Rheumatoid Arthritis Interstitial Lung Disease Mice
Abstract
Background Rheumatoid arthritis interstitial lung disease (RA-ILD) is one of the most common complications of rheumatoid arthritis (RA) that severely impairs the quality of life and survival. Zang Bi Formula (ZBF) is mostly used in clinical practice for patients with recurrent occurrence of RA. However, its mechanism of action and efficacy in RA-ILD still remain unclear. Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD. Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD. Methods From January 2022 to March 2023, a total of 14 tumor necrosis factor alpha-transgenic (TNF-Tg) mice were randomly divided into Saline group and ZBF group, with 7 mice in each group. At the same time, 7 wild-type (WT) mice in the same litter were randomly selected as the control group (WT group). Intragastric administration of ZBF 1.4 g/mL with 0.2 mL per time was given to mice of ZBF group once a day, and those in the WT group and Saline group were given an equal amount of normal saline via intragastric administration. After the intervention for 8 weeks, hematoxylin&eosin (H&E) staining of mouse ankle tissues was performed to observe the inflammatory cell area. Alcian blue-orange and tartrate-resistant acid phosphatase (TRAP) staining was performed to observe the cartilage area and bone area ratio, as well as the osteoclast area, respectively. The area proportion of inflammatory cells, fibrosis and T-cell/B-cell proportion in mouse lung tissues were observed by H&E staining, Masson staining and immunofluorescence staining, respectively. Results Mice in the Saline group had significantly increased inflammatory cell infiltration, synovial hyperplasia, and ankle tissue destruction. Inflammation of the ankle joint was alleviated in the ZBF group. The proportion of inflammatory cells in the Saline group was significantly higher than that of the ZBF group and WT group, which was significantly higher in the ZBF group than that of the WT group (P<0.05). Mice in the Saline group had significant damages to the sagittal plane of the talus of the ankle joint and bone erosion. Bone damages of the ankle joint and erosion were significantly alleviated in ZBF group, showing a gradually cleared boundary of the sagittal plane of the talus and increased bone mass. The proportions of cartilage area and bone area in the Saline group were significantly lower than those of ZBF group and WT group, which were significantly lower in the ZBF group than those of WT group (P<0.05). Mice in the Saline group presented massive infiltration of red-stained osteoclasts in the ankle joint, which was significantly alleviated in mice of ZBF group. The area of osteoclasts in the ZBF group was significantly smaller than that of the Saline group (P<0.05). Mice in the Saline group had mild-to-moderate inflammatory cell infiltration diffusely around the pulmonary interstitium, blood vessels and bronchi, thickening of the walls of the middle and small arteries, reduced alveolar intervals and obvious damages to lung tissues. Inflammatory cells infiltrated in the pulmonary interstitium surrounding tissues of the trachea and blood vessels were reduced and the boundary of the lungs were cleared in mice of ZBF group, presenting an improved lung structure. The proportion of inflammatory cells area in the Saline group was significantly higher than that of the ZBF group and WT group, which was significantly higher in the ZBF group than that of the WT group (P<0.05). Mice in the Saline group had significantly enlarged areas of blue collagen fibers around blood vessels and trachea and thickening of the alveolar or bronchial walls. Mice in the ZBF group had reduced areas of blue collagen fibers around blood vessels and trachea and improved lung structure. Pulmonary fibrosis scores of the lung were significantly higher in the Saline group than those of ZBF group and WT group, which were significantly higher in the ZBF group than those of WT group (P<0.05). T lymphocytes cells and B lymphocytes cells increased significantly in mouse lung tissue of the Saline group, and most of them surrounded the pulmonary blood vessels and bronchi, forming a follicle-like structure lacking a germinal center. The follicle-like structures were less observed in mouse lungs of the ZBF group. The area proportions of B lymphocytes cells and T lymphocytes cells in the Saline group were significantly higher than those of the ZBF group and WT group, which were significantly higher in the ZBF group than those of WT group (P<0.05) . Conclusion ZBF not only reduced ankle injury in TNF-Tg mice, but also improved their lungs inflammation and fibrosis, reducing the numbers of B lymphocytes cells and CD3+ T lymphocytes cells in lung tissue.
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