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Objective@#To investigate the therapeutic and immunomodulatory effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on adjuvant arthritis(AA) rats.@*Methods@#Twenty-four male Sprague-Dawley(SD) rats were established with AA by complete Freund's adjuvant method.They were randomly divided into model group and hUC-MSCs group (2×106 cells/mL, 5×106 cells/mL, tail vein injection), and the Yisaipu group (2.8mg/kg, subcutaneous injection), 6 rats in each group.Another 6 male SD rats were used as the control group.After the model was established, the body weight and paw volume were recorded weekly, the whole body score and the arthritis index score were calculated, and the joint swelling number was calculated.The animals were sacrificed after d35, the weight of thymus and spleen were weighed, and the corresponding index was calculated, the histopathological changes of the ankle joint were observed by HE staining.The percentages of CD4+ CD44+ T cell and CD4+ CD62L+ T cell were detected by flow cytometry.The levels of TNF-α, IL-1β in the serum of AA rats were detected by ELISA.@*Results@#hUC-MSCs relieved paw volume, the whole body score and arthritis index score, and the joint swelling number in AA rats (F=20.573, 89.092, 14.161, 10.914, all P<0.01). hUC-MSCs reduced thymus index[(0.120±0.032), (0.120±0.031)] and spleen index[(0.250±0.070), (0.240±0.018)] (F=6.339, 4.105, all P<0.01), improved structural damage of ankle joint.hUC-MSCs could regulate the percentage of T cell subsets(CD4+ CD62L+ )[(7.0±1.4)%, (7.9±2.2)%], (CD4+ CD44+ )[(15.0±3.6)%, (12.0±1.9)%] in spleen (F=6.331, 12.719, all P<0.01), and down-regulate the levels of TNF-α [(172.0±13.0)ng/L, (150.0±12.0)ng/L] and IL-1β [(75.0±36.0)ng/L, (74.0±20.0)ng/L] in serum (F=8.221, 3.581, all P<0.05) of AA rats by tail vein injection.@*Conclusion@#hUC-MSCs can promote the treatment of AA rats by regulating the function of T cells.
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To investigate the therapeutic and immunomodulatory effects of human umbilical cord-derived mesenchymal stem cells ( hUC-MSCs) on adjuvant arthritis (AA) rats.Methods Twenty -four male Sprague-Dawley( SD) rats were established with AA by complete Freund＇s adjuvant method.They were randomly divided into model group and hUC -MSCs group (2×106 cells／mL,5×106 cells／mL,tail vein injection),and the Yisaipu group (2.8mg／kg,subcutaneous injection ),6 rats in each group.Another 6 male SD rats were used as the control group.After the model was established ,the body weight and paw volume were recorded weekly ,the whole body score and the arthritis index score were calculated ,and the joint swelling number was calculated.The animals were sacrificed after d35,the weight of thymus and spleen were weighed ,and the corresponding index was calculated ,the histopathological changes of the ankle joint were observed by HE staining .The percentages of CD4 +CD44 +T cell and CD4 +CD62L+T cell were detected by flow cytometry.The levels of TNF-α,IL-1βin the serum of AA rats were detected by ELISA.Results hUC-MSCs relieved paw volume ,the whole body score and arthritis index score ,and the joint swelling number in AA rats (F＝20.573,89.092,14.161,10.914,all P＜0.01).hUC-MSCs reduced thymus index[(0.120 ±0.032),(0.120 ±0.031)] and spleen index[(0.250 ±0.070),(0.240 ±0.018)] ( F＝6.339,4.105,all P＜0.01),improved structural damage of ankle joint.hUC-MSCs could regulate the percentage of T cell subsets(CD4 +CD62L+)[(7.0 ±1.4)%,(7.9 ±2.2)%],( CD4 +CD44 +) [(15.0 ±3.6)%,(12.0 ± 1.9)%] in spleen (F＝6.331,12.719,all P＜0.01),and down -regulate the levels of TNF -α[(172.0 ± 13.0)ng／L,(150.0 ±12.0)ng／L] and IL-1β[(75.0 ±36.0)ng／L,(74.0 ±20.0)ng／L] in serum (F＝8.221, 3.581,all P＜0.05) of AA rats by tail vein injection.Conclusion hUC-MSCs can promote the treatment of AA rats by regulating the function of T cells.
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Objective To establish and evaluate a rat model presenting symptoms of arthritis-hypertension disease (AHD).Methods A total of forty healthy 5-6 week-old male SD rats were used in this study.Hypertension was induced by constriction of the left renal artery by two kidney one clip (2K1C) with a 0.25 mm silver clamp, and AHD model was established by injecting 0.1 mL complete Freund adjuvant to the left hind paw.Tail artery pressure was measured with a non-invasive blood pressure measurement system.The degree of swelling in the non-inflammatory joint of rats was measured with a paw volume measuring instrument, the arthritis index and incidence of inflammation were evaluated.The rats were sacrificed on the 35th day.The thoracic aorta, ankle joint and spleen tissues were examined by pathology using HE staining.Results The joint of AHD model rat was significantly swollen, extensive synovial cell hyperplasia, inflammatory cell infiltration, vascular pannus formation, and bone and cartilage destruction.The number of germinal centers in spleen was increased, and a large number of lymphocyte infiltration, diffuse proliferation of white pulp, and red pulp infiltration were present.The arthritis index, incidence of inflammation and histopathological scores of the joint and spleen were significantly higher than adjuvant arthritis (AA) rats;meanwhile, the blood pressure of AHD model rat was significantly increased, the thickness and cross-sectional area of thoracic aorta were significantly increased, while the lumen diameter was significantly reduced.The blood pressure and vascular injury were significantly increased or aggravated compared with the HT rats.Conclusions A rat model of arthritis-hypertension disease is successfully established by using complete Freund adjuvant intradermal injection to the footpad and surgery to narrow the left renal artery.
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Objective To investigate the effects and partial mechanism of prednisone and TACI-Ig combination on MRL/Mpslac-lpr ( MRL/lpr) mice. Methods MRL/lpr mice were randomly divided into 6 groups, which includ-ed model group, prednisone (2. 5, 5. 0 mg/kg) group, TACI-Ig (15. 0 mg/kg) group, prednisone and TACI-Ig combination [(2. 5+7. 5) mg/kg, (2. 5+15. 0) mg/kg] group. BALB/c mice were set as normal group. Pred-nisone was given intragastrically everyday and TACI-Ig was given subcutaneously every two days for 13 weeks. In the meantime, the normal and model group were treated with an equal volume of normal saline. The general sign and proteinuria level were observed in the treatment period. The sections of spleen and kidney tissues for pathologi-cal analysis were stained with HE. Serum levels of auto-antibodies and BAFF were detected by ELISA kit. The per-centage of plasma cells and CD138 expression in the spleen were detected by flow cytometry analysis and immuno-histochemistry, respectively. Results The skin damage and the proteinuria level were improved and decreased by prednisone and TACI-Ig combination treatment. The spleen and kidney pathology were also improved including re-ducing germinal center formation and alleviating the glomerular fibrosis, mesangial cell hyperplasia and inflammato-ry cell infiltration, respectively. What was more, the percentage of splenic plasma cells ( CD19 -CD138 +) was re-duced significantly, which maybe resulted in the decrease in ANA. However the high level of anti-dsDNA antibody was not influenced by the combination treatment. The serum level of BAFF was also reduced by the combination treatment. Conclusion Prednisone and TACI-Ig combination treatment has a beneficial effect on murine SLE, which may be associated with the inhibition of plasma cell differentiation and the secretion of auto-antibody.
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ObjectiveTo study the pharmacokinetics of iguratimod in rats. MethodsThe concentration ofiguratirnod in the samples was determined by HPLC method. The pharmacokineties parameters were calculated withDAS softwrare. ResultsThe mainpharmacokineties parameters of normal group(6mg/kg) were as follows:t1/2Ke:3.56h, tpeak: 4.00h, Cmax : 8.87μg/ml, AUC0.24 : 74.76μg· ml-1·h-1. The main pharmacokineties parameters of threemodel groups(3,6,12mg/kg) were as follows: t1/2Ke: 4.54,3.20,3.17h, tpcak:3.83,3.83,4.67h,Cmax:3.84, 8.31,12.69μg/ml, AUC0.24 :40.21,76. 72,117.06μg·ml-1·h-1. Except Cmax and AUC, no significant differenceswere found between the three model groups. And the differences between normal group and model group were notsignificant. ConclusionThe pharmacokinetics of rats ks fit to one-compartment model.
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Objective To establish a model in rats for studying the lung injury induced by powder combustion. Methods The explosion box and trauma chamber were constructed based on the fire simulation-platform. The smoke composition was analyzed on-line. The animal clinical manifestation was observed, and the lung water ratio, arterial blood gases, gross appearance and macropathology were analyzed to evaluate the injury level. Results The smoke contents included CO, SO 2, NO and NO 2. When the injury occurred, the CO concentration was 505 23 ppm, and SO 2 concentration was 67?4.8ppm. The time to cause injury was 4 minutes. The tachypnea immediately occurred for most of the rats, then bradypnea and dyspnea. The metabolic acidosis happened at the early stage of injury and the combined effects of metabolic acidosis and respiratory acidosis appeared at the late stage. Water ratio in the lung gradually increased and reached the peak at 6 hours later, and the normality was not recovered after 24 hours. The gross appearance and macropathology proved the lung injury. The obvious bleeding appeared at 4 hours, and the edema reached the most grievous level at 6 hours, and the normality was not recovered after 24 hours. Conclusion The model has been successfully established to study powder combustion-induced acute aspiration lung injury in rats .This model can keep the injury conditions stably and has the benefits of easy-making and repeatable.
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AIM To investigate the effect of melatonin on collagen-induced arthritis (CIA). METHODS The model of mice CIA was prepared and the change of secondary paw-swelling and the mean scores of arthritis were observed. The level of PGE was assayed by spectrophotometer; Meanwhile, 3H-TdR incorporation was used to detect ConA-and LPS-induced splenocytes proliferation and the production of interleukin (IL)-1 and IL-2. Hepatic pathological examination was performed by Hematoxylin-eosin (HE) stain method. RESULTS Treatment of ig melatonin(10,100, 1 000 ?g?kg -1) significantly decreased inflammation of the arthritis. The increased ConA-induced splenocytes proliferation ,PGE, IL-1 and IL-2 production in mice CIA were reversed by melatonin. Meanwhile, the pathological examination showed that articulus cartilage degeneration with synovial hyperplasia and inflammatory cells infiltration in CIA mice was suppressed by ig melatonin. CONCLUSION Melatonin has inhibitory effect on mice CIA which may be related to its immunoregulative function.