Effect Of Drug Dispense Interval On Therapeutic Efficacy Of Thymopentin On Myasthenia Gravis

OBJECTIVE:Although several therapeutic programs are currently available for the treatment of myasthenia gravis(MG),the previous study in our lab suggested that thymopentin (TP-5) is effective for improving the pathologic parameters found in the experimental autoimmune myasthenia gravis(EAMG). For the purpose of probing the changes of CD₄⁺/CD₈⁺ in EAMG mice after the TP-5 therapy at different drug dispense intervals,the DNA content,the membrane fluidity, Ca2+-ATPase, Na+,K+-ATPase and Superoxide dismutase (SOD) of skeletal muscle cells in EAMG were studied. METHOD: Forty C57BL/6 mice were randomly divided into five groups—normal control group, EAMG group, EAMG with daily peritoneal injection(ip) of TP-5 (groupâ… ), EAMG with ip TP-5 every two days (groupâ…¡), and EAMG with ip TP-5 every four days (groupâ…¢). Fragment of targeting peptides of nicotinic acetylcholine receptors (nAChR) was used to immunize C57BL/6 mice to establish the EAMG model. The three treatment groups received the same amount of TP-5 through the experiment period. Their CD4+ and CD8+ in peripheral blood were measured after two weeks of TP-5 therapy. The content of DNA in skeletal muscle cells,membrane fluidity,Na+,K+-ATPase,Ca2+-ATPase and SOD of TP-5 every two days group , normal control group and EAMG group were tested. RESULT:The CD₄⁺/CD₈⁺ ratio of MG group was significantly higher than that of normal group(P < 0.01). All values of CD₄⁺/CD₈⁺ in the three TP-5 groups were fall in between of normal and EAMG mice, suggesting a positive regulating effect of TP-5 on MG. The CD₄⁺/CD₈⁺ ratio in groupâ… was 1.037±0.402, still significantly higher than the value of 0.672±0.139 in normal group (P < 0.01), but not different from that of MG group. The CD₄⁺/CD₈⁺ ratio in groupâ…¢was 0.952±0.253, closer than groupâ… toward normal, yet no statistic differences from the value of normal or EAMG group. The CD₄⁺/CD₈⁺ ratio in groupâ…¡was 0.832±0.115 , which was no difference from normal value, but significantly lower than the value of 1.112±0.216 in MG group (P < 0.05). For the values of DNA content and membrane fluidity, the MG group was significantly lower than the normal group (P < 0.001), and the treatment of TP-5 reversed the values in MG group to the normal. The SOD levels were found to be no differences among the normal, MG model and TP-5 groups. The activities of Na+,K+-ATPase and Ca2+-ATPase were found to be lower in MG group than that in normal group(P < 0.001), however the TP-5 therapy did not raise but decrease these enzyme activities(P < 0.001). CONCLUSION:Compared to the normal group, MG increased the CD₄⁺/CD₈⁺ ratio, decreased the membrane fluidity as well as the activities of Na+,K+-ATPase and Ca2+-ATPase, did not change the SOD activities but increase the DNA content of skeletal muscles. The TP-5 therapy reversed the pathologic value of CD₄⁺/CD₈⁺ ratio toward normal, and its immune regulating effect showed the best result when the drug was dispensed at every other day interval. The TP-5 therapy converted the abnormal values of DNA content and membrane fluidity toward normal, showed no effect on SOD activities, and decreased the activities of ATPases.