RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Zhuangjin Decoction (BZD) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: This study aimed to verify the mechanism of Bushen Zhuangjin Decoction in relieving the pain of knee osteoarthritis. MATERIALS AND METHODS: Network pharmacology evaluation was used to discover the potential targets of BZD to relieve pain in KOA. The therapeutic effects of BZD treatment on KOA pain using histomorphology, behavioral assessments, suspension chip analysis, and ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) assays. The functional magnetic resonance imaging was used to explore the effects of BZD treatment on brain function associated to KOA. RESULTS: Network pharmacological analysis revealed the association between the analgesic effect of BZD on KOA and the pain signaling neurotransmitter 5-HT. Subsequently, we conducted experiments to verify the therapeutic effect of BZD on pain in KOA animal models. Behavioral tests demonstrated that the pain threshold of knee osteoarthritis rats decreased in PWT and PWL, but BZD was able to increase the pain threshold. Histopathological staining indicated thinning of the cartilage layer and sparse trabeculae in the subchondral bone. Suspension chip analysis revealed a significant increase in pro-inflammatory factors of IL-1α, IL-5, IL-12, IL-17A, RANTES, TNF-α and M-CSF in KOA, along with a significant decrease in anti-inflammatory factor of IL-13. However, BZD treatment decreased the expression of pro-inflammatory factors and increased the content of anti-inflammatory factor. UHPLC-MS/MS analysis showed a significant decrease in the serum levels of GABA, E, GSH, Kyn, Met, and VMA in KOA, which were significantly increased by BZD. Conversely, the serum levels of TrpA, TyrA, Spd, and BALa were significantly increased in KOA and significantly decreased by BZD. ELISA and Western blot analysis showed increased expression of subchondral bone pain-related neuropeptides SP, CGRP, TH, NPY, VEGFA, 5-HT3 in KOA, which were decreased in BZD. Functional magnetic resonance imaging demonstrated that BZD exerts its therapeutic effect on KOA by modulating the activity and functional connections of the cortex, hypothalamus, and hippocampus. CONCLUSIONS: This study confirmed the significant role of pain-related neuromodulation mechanisms in the analgesic therapy of BZD and provides a theoretical foundation for using BZD as a traditional Chinese medical treatment for KOA pain.
Assuntos
Medicamentos de Ervas Chinesas , Osteoartrite do Joelho , Ratos , Animais , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/metabolismo , Espectrometria de Massas em Tandem , Dor/tratamento farmacológico , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêuticoRESUMO
BACKGROUND: Spontaneous femoral neck fracture is a rare condition that remains controversial due to limited reported cases. This retrospective study aims to provide further insights into the etiology and characteristics of the disease. METHOD: We conducted a retrospective review of data from 963 patients with femoral neck fractures. The data encompassed demographic information, medical histories, radiographic records, bone mineral density (BMD) measurements, and pathological examinations. Patients were categorized into two groups: spontaneous femoral neck fracture (SFF) group (30 cases) and control group (933 cases), based on their medical histories. Logistic regression analysis was employed to identify risk factors for SFF. Statistical analysis was performed to compare and elucidate the characteristics of SFF within each group. RESULTS: Logistic regression analysis revealed osteonecrosis of the femoral head, steroid use, and osteoporosis as three significant risk factors for SFF. Furthermore, a higher proportion of Garden type I and II fractures, as well as Pauwels type I fractures, were observed in the SFF group compared to the control group. Within the SFF group, a higher proportion of patients with osteonecrosis exhibited Garden type III and IV fractures compared to those with osteoporosis. Additionally, both magnetic resonance imaging (MRI) and pathological examinations demonstrated that osteonecrosis in the SFF group predominantly occurred at the lateral femoral head-neck junction. CONCLUSIONS: Osteonecrosis of the femoral head, particularly involving the lateral head-neck junction, was confirmed as a major risk factor for SFF. Furthermore, SFF exhibits internal heterogeneity based on its different causes.