ABSTRACT
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.
ABSTRACT
AIM: To investigate the effects of three extracts of Fufang Dihuang decoction on the relaxation of mesentery artery in streptozotocin(STZ)-induced diabetic rats. METHODS: Diabetic rat model was induced by i.p injection STZ at a dosage of 60 mg?kg~ -1 . 30 d later, 95% ethanol, 70% ethanol or water extract of Radix Rehmanniae was p.o administrated for 30 d at the dosage of 107.8 , 154.7 and 56.8 mg?kg~ -1 , respectively. On the 60th day, the responses of mesentery artery were determined in the absence or presence of L-argine (L-Arg), N-Nitro-L-argine (NLA) and Indomethacin (Ind). RESULTS: The relaxation of mesentery artery of diabetic rat was diminished compared with the normal control. The basal release of NO and the L-argine-induced release of NO decreased 64.6 %, 77.6 % respectively in diabetic group compared with the normal control, with the decreased proportion of NO in the endothelium dependent relaxation. 95% and 70% ethanol extract of Fufang Dihuang decoction ameliorated the impaired release of NO in rat's mesentery artery. CONCLUSION: Abnormal relaxation of mesentery artery in diabetic rat may be due to the decreased releasing of NO. The extracts of Fufang Dihuang decoction can protect the endothelium cells and improve the relaxation of mesentery artery, among them 70% ethanol extract exert the best potency, followed by 95% ethanol extract. And the water extract has a poor effect.