RESUMO
OBJECTIVES: To observe the effect of acupuncture stimulation of "Yanglingquan"(GB34), "Zusanli"(ST36) and "Xuanzhong" (GB39) on arthritis index (AI), joint synovial membrane pathology, serum-related immunoinflammatory factors, and expressions of tumor suppressor gene mt-p53, nuclear factor kappa B (NF-κB) and peroxisome proliferator activated receptor gamma (PPARγ) in knee joint synovial tissue of rats with type â ¡ collagen-induced arthritis (CIA), so as to explore its possible mechanisms underlying improvement of rheumatoid arthritis (RA). METHODS: Male SD rats were used in the present study. The CIA model was established by subcutaneous injection of collagen emulsion (200 µL/rat) in the tail root region on the first day and repeat (100 µL/rat) once on the 9th day. Eighteen successful CIA rats were randomized into model, medication and acupuncture groups, with 6 rats in each group. Other 6 normal rats were used as the normal control group. For rats of the medication group, leflunomide (1.9 mg/kg) was administrated by gavage, once a day, and for rats of the acupuncture group, manual acupuncture stimulation was applied to bilateral GB34, ST36, GB39 for 30 min, once a day, for 12 weeks. The arthritis index (AI) score (0-4 points) was evaluated once every week. The contents of IL-6, IL-17 and TNF-α in the serum were determined by ELISA. Histopathological changes of the ankle joint were observed by H.E. staining. The protein and mRNA expression levels of mt-p53, NF-κB p65, and PPARγ in the knee joint synovial tissue were determined by Western blot and quantitative real time PCR, separately. RESULTS: Compared with the normal control group, the AI scores at different time-points after modeling, contents of serum TNF-α, IL-6 and IL-17, expression levels of mt-p53, NF-κB p65, PPARγ proteins and mRNAs were significantly increased in the model group (P<0.01, P<0.05). In comparison with the model group, the AI scores at the 10th week in the medication group and at the 3rd, 9th and 10th week in the acupuncture group, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of mt-p53 and NF-κB p65 proteins in both medication and acupuncture groups, as well as mt-p53 and NF-κB p65 mRNAs in the medication group were apparently decreased (P<0.01, P<0.05), while the expression levels of PPARγ protein in both medication and acupuncture group and PPARγ mRNA in the medication group were significantly up-regulated (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in down-regulating the AI score and serum TNF-α, IL-6 and IL-17 contents. The effect of acupuncture was weaker than that of medication in down-regulating the expression of mt-p53 and NF-κB p65 proteins and mRNAs and in up-regulating PPARγ mRNA (P<0.01). H.E. results showed ankle cartilage hyperplasia, reduced joint cavity, mild fibroproliferation and inflammatory cell infiltration in the surrounding soft tissue of the ankle joint in rats of the model group, which was milder in both medication and acupuncture groups. CONCLUSIONS: Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.
Assuntos
Terapia por Acupuntura , Artrite Experimental , Artrite Reumatoide , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Interleucina-17/genética , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Proteína Supressora de Tumor p53/efeitos adversos , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Artrite Reumatoide/induzido quimicamente , Artrite Experimental/genética , Artrite Experimental/terapia , RNA MensageiroRESUMO
Previous studies have implicated erythropoietin (EPO) signaling in the regulation of glucose metabolism. Whether EPO can be used treat diabetes and the underlying mechanism remain to be elucidated. The present study aimed to investigate whether EPO affects glucose metabolism, and the underlying mechanisms, in experimental diabetic rats. The effects of EPO (300 U/kg three times a week for 4 weeks) on glucose metabolism, hematopoietic function, blood selenium content and the ultrastructure of pancreatic ßcells were investigated in low dose (25 mg/kg body weight) streptozotocininduced experimental diabetic rats provided with a highfat diet. The results demonstrated that EPO significantly decreased the fasting blood glucose, the area under the curve of the oral glucose tolerance and insulin tolerance tests and Lalanine gluconeogenesis. Ultrastructural examination of the pancreatic islets revealed that EPO prevented the dysfunction of pancreatic ßcells in experimental diabetic rats, ameliorated cytoplasmic vacuolation and fragmentation of mitochondria, and increased the number of secretory granules. EPO administration increased the activities of superoxide dismutase and glutathione peroxidase, and decreased the level of malondialdehyde. Additionally, EPO increased blood selenium in the diabetic rats and produced a hematopoietic effect. These results indicated that EPO modulated glucose metabolism and improved pancreatic ßcells damage by increasing antioxidation. The detailed mechanisms underlying these effects require further investigation.