RESUMO
Objective To investigate the effect of Terminalia chebula water extract (TCWE) on the cellular immunity and PD-1/PD-L1 pathway in rats with collagen-induced arthritis (CIA). Methods SD rats were randomly divided into four groups: a control group, a CIA group, a TCWE group and a methotrexate (MTX) group, with 15 rats in each group. Except for the control group, SD rats in other groups were subcutaneously injected with type II collagen to establish the model of collagen-induced arthritis (CIA). The rats in the TCWE group were treated with 20 mg/(kg.d) TCWE and the rats in the MTX group were treated with 1.67 mg/(kg.d) MTX. After 14 days of treatment, the cartilage morphology was examined using hematoxylin-eosin (HE) staining, and splenic T lymphocyte apoptosis and Treg/Th17 cell ratio were detected by flow cytometry. The mRNA expressions of retinoid-related orphan nuclear receptor γt (RORγt), forkhead box P3 (FOXP3), PD-1 and PD-L1 in spleen were detected by reverse transcription PCR. The expression and localization of RORγt and FOXP3 were detected by immunohistochemical staining. The protein expressions of PD-1 and PD-L1 in splenic lymphocytes were detected by Western blot, and the levels of serum interleukin 17 (IL-17) and transforming growth factor ß (TGF-ß) in rats were detected by ELISA. Results Compared with CIA group, the pathological changes of cartilage and synovium were significantly alleviated in the TCWE group and the MTX group. Both the apoptosis rate of T lymphocytes in spleen and the ratio of Treg/Th17 cells increased. The expression of RORγt decreased, while the expressions of FOXP3, PD-1 and PD-L1 increased in spleen lymphocytes. The level of serum IL-17 decreased, while the level of serum TGF-ß increased. Conclusion TCWE treatment may activate PD-1/PD-L1 pathway in spleen cells to regulate cellular immunity, thus reducing cartilage injury in CIA rats.
Assuntos
Artrite Experimental , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Ratos Sprague-Dawley , Baço , Terminalia , Animais , Artrite Experimental/imunologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Ratos , Terminalia/química , Masculino , Imunidade Celular/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Extratos Vegetais/farmacologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Células Th17/metabolismoRESUMO
[Figure: see text].