Effect of butylphthalide intervention on experimental autoimmune myositis in guinea pigs.

Idiopathic inflammatory myopathies are a group of rare muscular diseases that are characterized by acute, subacute or chronic proximal and symmetric muscle weakness, muscle fiber necrosis and infiltration of inflammatory cells, particularly activated CD8+ cytotoxic T cells and phagocytes. 3-n-butylphthalide (NBP) protects mitochondria and reduces the inflammatory response in multiple disease models. In myositis, it has remained elusive whether NBP can protect muscle cells from muscle fiber injury. Experimental autoimmune myositis (EAM) was induced in a total of 40 guinea pigs by myosin immunization. After 4 weeks, low- or high-dose NBP solution was intraperitoneally injected. Saline solution was used as a negative control. After 10 days, the clinical manifestations were assessed by determining rodent grasping power, histopathological changes, Ca2+-adenosinetriphosphatase (ATPase) activity by an ATPase kit, and mRNA expression of interferon (IFN)-γ, retinoic acid receptor-related orphan nuclear receptor (ROR)γt and forkhead box (Fox) p3 in muscle tissue by reverse-transcription quantitative polymerase chain reaction analysis. It was demonstrated that NBP improved the myodynamia of guinea pigs with EAM and reduced the pathological inflammatory cell infiltration in a dose-dependent manner. NBP improved the Ca2+-ATPase activity of the muscle mitochondrial membrane and muscle plasma membrane in animals with EAM. It also reduced the mRNA expression of IFN-γ and RORγt, and significantly increased the mRNA expression of Foxp3 in muscle tissue. These results provided a basis for the consideration of NBP as a novel agent for the treatment of myositis and other muscular diseases associated with autoimmunity and inflammation.