| Objective: In order to look for available therapeutics for MS and to investigate the mechanism of occurrence and development of EAE and to clarify the therapeutic mechanism of Simvastatin and the role of p53 and IL-6 in EAE, we try to treat EAE by Simvastatin and observe expression changes of p53, IL-6, TNF-αand TGF-βand interreaction of cytokines and P53, taking triptolide as positive control.Methods: 55 female Wistar rats, weighing 150-200g, were divided into 4 groups: EAE group(15), Simvastatin treatment group(15), triptolide treatment group(15) and normal control group(10) randomly. Antigen homogenate is made by mixing healthy Guinea pig spinal cord homogenate and Complete Freund's adjuvant. Animal model is induced by hypodermic injection of 0.4ml antigen homogenate on left hind limb foot pad per rat and 0.05ml prtussis toxin on left hind limb foot pad per rat. From first day after immune, Simvastatin treatment group were given peritoneal injection of 1mg/Kg.d Simvastatin active compound per rat. Triptolide treatment group were given peritoneal injection of 40□/Kg.d triptolide per rat. EAE group and normal control group were given peritoneal injection of aequale normal sodium simultaneouly. From 11th day to 18th day after immunization, experimental animals were executed, scores of symptom and changes of body weight were recorded. Brain and spinal cords were extracted for pathology observation and immunohistochemistry dyeing of p53, IL-6, TNF-αand TGF-β. Staining intensitiy of p53, IL-6, TNF-αand TGF-βwas semiquantitatively analysised with BI2000 image analytical system. Statistical analysis were done with SPSS11.0 statistic software.Results: In EAE group, morbidity is 80.00%, mean body weight loss is 18.13±5.00g,mean score of symptom is 2.33±1.75, mean number of focus of infection is 16.20±7.78, mean onset date is 12.83±1.90;In statins group, morbidity is 40.00%, mean body weight loss is 12.27±4.95g,mean score of symptom is 0.83±1.28, mean number of focus of infection is 9.13±6.75, mean onset date is 15.00±1.41;In TP group, morbidity is 46.7%, mean body weight loss is 17.27±6.69g,mean score of symptom is 1.07±1.43, mean number of focus of infection is 10.45±7.53, mean onset date is 12.43±1.62.The differences of morbidity, change of body weight, scores of symptom, number of focus of infection and onset date between Simvastatin treatment group and EAE group were statistically significant (p<0.05). Expressions of TGF-βand p53 were increased, while the expressions of IL-6 and TNF-αwere decreased in Simvastatin treatment group(p<0.05). Only clinical symptoms and foci of infection have differences between Triptolide treatment group and EAE group(p<0.05). Expressions of TNF-αwere suppressed in EAE group(p<0.05). There is negative correlation between gray scale of IL-6 and scores, p53 and IL-6,... |
