Objective: Rheumatoid arthritis (RA) is a kind of chronic inflammatory disease characterized by the release of inflammatory cytokines and cardiomyocyte apoptosis, which lead to increased riskfor heart diseases. This study aims to explore the possible effect and mechanism of Celastrol on RA induced cardiac impairments in rats. Methods: Collagen induced RA wistar rat models (CIA) were established for the measurement on secondary foot swelling degree, polyarthritis index score, spleen and thymus index. Pathological morphology was observed using Hamp;E staining. Heart fibrosis was measured after Sirius red staining, while cell apoptosis was determined by TUNEL staining. For in vitro experiments, rat cardiomyocytes were isolated to determine the inflammatory cytokine secretion and cell apoptosis using ELISA and flow cytometry, respectively. Protein expressions of related index and autophagy were detected by Western blot and immunofluorescence. Results: CIA rat model was successfully established and characterized by severe secondary foot swelling degree, and increased polyarthritis index score and spleen and thymus index. Synovial hyperplasia, disordered cardiomyocytes, cell infiltration and fibrosis were also observed in CIA rat model. Compared with CIA model, Celastrol treatment could suppress the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β, as well as inhibiting the expressions of Bax, cleaved caspase3, collagen I, collagen III and α-SMA. In addition to that, Celastrol treatment can attenuate cell apoptosis and fibrosis of cardiomyocytes and elevate Bcl-2 expression. RA induced cell autophagy can be suppressed by Celastrol through inhibiting the activation of TLR2/HMGB1 signal pathway. Conclusion: Celastrol can regulate TLR2/HMGB1 signal pathway to suppress autophagy and therefore exert cardioprotective effect in RA.
Int Arch Allergy Immunol

中文翻译：

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Celastrol 通过抑制 TLR2/HMGB1 信号通路介导的自噬对类风湿性关节炎发挥心脏保护作用

目的：类风湿性关节炎（RA）是一种以炎性细胞因子释放和心肌细胞凋亡为特征的慢性炎症性疾病，导致心脏病风险增加。本研究旨在探讨 Celastrol 对 RA 诱导的大鼠心脏损伤的可能作用和机制。方法：建立胶原诱导的RA wistar大鼠模型(CIA)，用于测量继发性足肿胀程度、多关节炎指数评分、脾和胸腺指数。使用Hamp;E染色观察病理形态。在天狼星红染色后测量心脏纤维化，而通过 TUNEL 染色确定细胞凋亡。对于体外实验，分离大鼠心肌细胞以分别使用 ELISA 和流式细胞术测定炎性细胞因子的分泌和细胞凋亡。Western印迹和免疫荧光检测相关指标和自噬的蛋白表达。结果：成功建立CIA大鼠模型，以继发性足部肿胀程度严重，多关节炎指数评分和脾胸指数升高为特征。在CIA大鼠模型中还观察到滑膜增生、心肌细胞紊乱、细胞浸润和纤维化。与CIA模型相比，Celastrol治疗可抑制炎症细胞因子的释放，包括TNF-α、IL-6、IL-1β，并抑制Bax、cleaved caspase3、I型胶原、III型胶原和α-SMA的表达。除此之外，Celastrol 治疗可以减弱心肌细胞的细胞凋亡和纤维化，并提高 Bcl-2 的表达。Celastrol可以通过抑制TLR2/HMGB1信号通路的激活来抑制RA诱导的细胞自噬。结论：Celastrol 可以调节 TLR2/HMGB1 信号通路抑制自噬，从而在 RA 中发挥心脏保护作用。
Int Arch 过敏免疫