RESUMO
Objective To explore the mechanism of the treatment of atrial fibrillation(AF)with traditional Chinese medicine compound of eliminating phlegm and removing blood stasis.Methods Sixty male SD rats were randomly divided into the blank group and the model group.Ach(66 μg·mL-1)-CaCl2(10 mg·mL-1)was injected into the tail vein for 7 consecutive days to establish the rat AF model.The rats with successful modeling were randomly divided into model group,high,medium and low dose groups of Chinese herbal compound and verapamil group.The high,medium and low dose groups of Chinese herbal compound were given 12.38 mg,6.18 mg and 3.10 mg·kg-1·d-1 Chinese herbal compound for removing phlegm and removing blood stasis solution by gavage,while the verapamil group was given 8.31 mg·kg-1·d-1 verapamil solution by gavage,and the blank group and model group were given equal volume distilled water by gavage.During this period,the rats were still given tail vein injection for 14 consecutive days.The duration of atrial fibrillation in lead Ⅱ of rats was measured by electrophysiological recorder,the ultrastructural changes of rat atrial muscle were observed by transmission electron microscope,the relative expression of CAV1.2,CaM,CaMKⅡ mRNA in rat atrial muscle was detected by RT-PCR,and the expression of CAV1.2,CaM,CaMKⅡ and downstream proteins RyR2,P-RyR2 in rat atrial muscle was detected by Western blot.Results Compared with the blank group,the rats in the model group showed typical atrial fibrillation ECG.Compared with the model group,the duration of atrial fibrillation in the compound Chinese medicine group decreased.The arrangement of myofilaments was relatively neat,and the structure of mitochondria was relatively complete;CAV1.2 mRNA and protein expression increased(P<0.05),CaM,CaMKⅡ mRNA and protein expression decreased(P<0.01),downstream protein P-RyR2 expression decreased(P<0.01),RyR2 protein expression had no difference(P>0.05).Conclusion The Chinese herbal compound for removing phlegm and removing blood stasis can shorten the duration of atrial fibrillation in rats,inhibit the ultrastructure damage of atrial myocytes,and its mechanism may be related to regulating the expression of CAV1.2/CaM/CaMKⅡ signal pathway and improving the disorder of calcium regulation.
RESUMO
Objective:To observe the effects of TCM compounds for eliminating phlegm and removing blood stasis on the ultrastructure of atrial myocardium in atrial fibrillation (AF) rats; To explore its possible mechanism.Methods:Totally 60 male SD rats were divided into blank group (10 rats) and model group (50 rats) according to random number table method. The atrial fibrillation model was established by tail vein injection of ACh-CaCl 2 mixture for 7 consecutive days, and then the rats with successful modeling were divided into model group, verapamil group, TCM compounds high-, medium- and low-dosage groups according to random number table method, with 10 rats in each group. TCM compounds high-, medium- and low-dosage groups were given Chinese herbal decoction 41.25, 20.63, 10.31 g/(kg?d) by gavage, respectively, and the verapamil group was given verapamil solution 25 g/(kg?d). The blank group and the model group were given an equal volume of normal saline by gavage for consecutive 14 days. After 14 consecutive days, electrophysiological recorder was used to measure the duration of atrial fibrillation in each group of rats; the changes of ultrastructure of atrial myocytes in each group were observed under transmission electron microscope; serum ROS, SOD and GSH-Px levels of rats were detected by ELISA. Results:Compared with the model group, the duration of atrial fibrillation in TCM compounds high-, medium- and low-dosage groups and verapamil group decreased ( P<0.05); the ultrastructural damage of atrial myocytes was improved; the content of ROS [(139.20±3.34) ng/ml,(139.00±3.28) ng/ml, (139.25±3.82) ng/ml vs. (155.60±7.32) ng/ml] in TCM compounds high- and medium-dosage groups and verapamil group decreased; the contents of SOD [(2.41±0.26) ng/ml, (2.40±0.12) ng/ml, (2.37±0.06) ng/ml vs.(2.12±0.21) ng/ml] increased ( P<0.05); the content of GSH-Px [(3.61±0.06) ng/ml, (3.60±0.08) ng/ml, (3.47±0.15) ng/ml, (3.51±0.19) ng/ml vs.(3.27±0.12) ng/ml] in TCM compounds high-, medium- and low-dosage groups and verapamil group increased ( P<0.05). Conclusion:TCM compounds for eliminating phlegm and removing blood stasis can shorten the duration of atrial fibrillation in rats, reduce the damage of ultrastructure of atrial myocytes in AF rats, regulate the expressions of serum ROS, SOD and GSH-Px in AF rats, and inhibit oxidative stress, which may be one of its mechanisms of action in the treatment of atrial fibrillation.
