Based on CAV1.2/CaM/CaMKⅡ Pathway to Explore the Mechanism of the Treatment of Atrial Fibrillation with Traditional Chinese Medicine Complex for Removing Phlegm and Removing Blood Stasis / 世界科学技术-中医药现代化

ABSTRACT

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.