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AIM: To investigate the CPU86017 and its enantiomers inhibit abnormal gene expression of calcineurin and NFκB in rat cardiomyopathy induced by L-thyroxin and compare the effect of CPU86017 (racemate) with its 4 enantiomers: (7S, 13R), (7S, 13S), (7R,13S), and (7R,13R)-CPU86017 in this model. METHODS: The animals were randomly divided into 7 groups. The rat hypertrophied model was produced by treatment with L-thyroxin 0.2 mg·kg-1·d-1, sc for 10 d and treated with CPU86017 or its enantiomers 4 mg·kg-1·d-1, sc from d 6 to d 10. The changes in left ventricular (LV) weight index, redox system, and the NO and iNOS activity in the myocardium were investigated. The expression of mRNA of calcineurin、NF-κB in the left ventricle was measured. RESULTS: There were significant cardiac hypertrophy and oxidative stress in rats treated by L-thyroxin. The expression of calcineurin, NFκB mRNA were upregulated (P<0.05, compared with that of control). After treatment with CPU86017 (racemate and enantiomers), LV remodeling and the redox system were improved. CPU86017 and (7S,13R)-CPU86017 showed a better improvement on LV remodeling and the redox than the other isomers and restored the normal expression of calcineurin, NF-κB (P<0.05, P<0.01), respectively. CONCLUSION: It suggested that an up-regulation of calcineurin and NFκB possibly related to the altered intracellular calcium handling system plays a role in the progression of L-thyroxin induced cardiomyopathy and CPU-86017 and its 7S,13R-CPU86017 enantiomer effectively inhibit the abnormal expression of calcineurin and NFκB genes, the NOS enzyme and oxidant stress in the cardiomyopathy.
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Objective:To study the influence of gonadal hormones on the function of lymphocytes of SLE patients through detecting the expression of estrogen receptor alpha(ER?) and the function of peripheral blood lymphocytes of SLE patients.Methods:Blood samples of 33 SLE patients and 31 normal controls were collected.Estradiol(E2) and testosterone (T) concentration in peripheral blood were detected by ELISA,the proliferating reaction of T lymphocyte stimulated by ConA were detected by methyl thiazolyl tetrazolium (MTT) assay and the expression of estrogen receptor alpha(ER?)mRNA of peripheral blood mononuclear cells (PBMCs),T lymphocytes and B lymphocytes were detected by RT-PCR.Results:Compared with normal control,the stimulating index of T lymphocyte proliferation decreased(P
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Objective:To investigate the expression of aromatase of renal tissue in systemic lupus erythematosus(SLE)model mice.Methods:BALB/c mice were induced SLE with homologuous splenic cell activated with ConA after being ovariectomized,and in the same time administered different doses of benzestrofol.E2 in peripheral blood and renal tissue was detected by ELISA and the expression of mRNA of aromatase in renal tissue was detected by RT-PCR in the 4th,6th,8th and 10th weeks.Results:The level of E2 of peripheral blood and renal tissue of SLE model mice became higher as benzestrofol exogenously administered heightened.Compared with control mice,the level of E2 in SLE model mice increased,and the expression of mRNA of aromatase of renal tissue increased with E2 increment.Conclusion:E2 promotes development of SLE through regulating expression of aromatase mRNA.