Dantrolene, a stabilizer of the ryanodine receptor, prevents collagen-induced arthritis.

Dantrolene, a stabilizer of the ryanodine receptor, prevents collagen-induced arthritis.
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Dantrolene 是兰尼碱受体的稳定剂,可预防胶原诱导的关节炎。

DOI:
10.1016/j.bbrc.2022.07.111
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发表时间:
2022
期刊:
Biochem Biophys Res Commun.
影响因子:
--
通讯作者:
Yano M.
Yano M.
中科院分区:
--
文献类型:
--
作者:
58)Nawata T;Sakai H;Honda T;Otsuka M;Fujita H;Uchinoumi H;Kobayashi S;Yamamoto T;Asagiri M;Yano M.

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Dantrolene 可抑制不稳定的兰尼碱受体的 Ca2+ 泄漏,因此可作为治疗内质网应激相关疾病的药物。然而,其治疗自身免疫性疾病的有效性仍不清楚。在这里,我们研究了丹曲林对小鼠胶原诱导性关节炎 (CIA) 的影响。口服丹曲林后,雄性和雌性 CIA 小鼠的关节炎评分均显着低于对照小鼠。微型计算机断层扫描和组织学分析表明,丹曲林可抑制骨和软骨破坏。血清抗II型胶原(CII)IgG水平与关节炎评分呈正相关(r=0.704,p<0.01)。此外,丹曲林组的血清抗 CII IgG 水平显着低于对照组(p < 0.05)。这些结果表明,对 CIA 小鼠口服丹曲林可抑制血清抗 CII IgG 的产生,从而预防关节炎。因此,丹曲林可能是一种潜在的抗风湿药物。
Dantrolene inhibits Ca2+leakage from destabilized ryanodine receptors and therefore may serve as a therapeutic agent against endoplasmic reticulum stress-associated diseases. However, its effectiveness in treating autoimmune diseases remains unclear. Here, we investigated the effect of dantrolene on collagen-induced arthritis (CIA) in mice. Oral administration of dantrolene resulted in significantly lower arthritic scores in both male and female CIA mice than in the control mice. Micro-computed tomographic and histological analyses showed that dantrolene suppressed bone and chondral destruction. The serum levels of anti-type II collagen (CII) IgG were positively correlated with the arthritic scores (r = 0.704,p< 0.01). In addition, the serum levels of anti-CII IgG were significantly lower in the dantrolene group than in the control group (p< 0.05). These results demonstrate that oral administration of dantrolene to CIA mice inhibits the production of serum anti-CII IgG and consequently prevents arthritis. Therefore, dantrolene may be a potential anti-rheumatic drug.
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