The Effect Of Intermittent Hypoxia And Rimonabant On Myocardial Ultrastructural And Myocardial Glucose Metabolism In Rats

Objective The present study aimed to discuss the effect of intermittent hypoxia(IH) and the antagonism of cannabinoid 1 receptors(CB1R)-rimonabant on myocardial ultrastructural and myocardial glucose Metabolism in Rats: involvement of expression of glucose transporter 4(GLUT4) in myocardial structure.Then we explored whether endocannabinoid system was involved in myocardial glucose metabolism.Methods Firstly, Thirty-two Sprague-Dawley male rats were randomly assigned into 4 groups: normal control(NC) group, intermittent hypoxia(IH)group, normal saline therapeutic intermittent hypoxia(IH+NS) group, rimonaban therapeutic intermittent hypoxia(IH+Rim) group.The rats of IH group,IH+NS group and IH+Rim were respectively placed into the same IH-chambers.Rats in NC group were exposed to the same timer- and valve-controlled changes as IH at normoxia levels throughout the protocol.All rats were killed after 28 days of exposure.Secondly,based on intermittent hypoxic ventilation, each rat of IH+Rim group was given Rimonabant 10ml·kg-1·d-1 by regular gavage, while rats of IH +NS group were simultaneously treated equal volume of normal saline. Third,after 28 days, we collected arterial blood of all rats via abdominal aortic puncture. Serum levels of fasting plasma glucose were detected by chemical colorimetric method, and radioimmunoassay was used to examine levels of fasting insulin,then calculated the Insulin resistance index and Insulin sensitivity index. We observed the myocardial ultrastructural and analyzed the mitochondria by the method of Flameng. Furthermore, we measured the expression of glucose transporter 4(GLUT4) and cannabinoid-1 receptor(CB1R) in both m RNA and protein levels in myocardial architecture.Results In the first part, compared with NC group, the contents of FINS,IRI and the m RNA and protein levels of CB1 R in IH group were higher, while the activities of ISI and the m RNA and protein levels of GLUT4 were lower(all p <0.05).In the second part,The myocardial mitochondria was damaged in IH group and the score of Flameng was increased(P <0.05)compared NC group. In the third part, Rimonabant can improve the damage of the mitochondria. IH group treated with the rimonabant showed a decrease in the levels of FINS, IRI, the expressions of CB1 R m RNA and the protein of CB1 R, Simultaneously it can increase in the activities of ISI, the expressions of GLUT4 m RNA and the protein of GLUT4(all P<0.05).In the fouth part, the contents of IRI was associated positively with the levels of the GLUT4 m RNA(r-0.677,P<0.01), but negatively correlated with the levels of the CB1 R m RNA(r 0.543,P<0.01). There was a significant negatively correlation between the levels of the GLUT4 m RNA and CB1 Rm RNA(r-0.800,P<0.01).Conclusions Firstly,IH can upregulate the CB1 R expression in both m RNA and protein levels and damage the mitochondria in myocardial structure of rats.The contents of IRI was associated positively with the levels of the GLUT4 m RNA in myocardial, but negatively correlated with the levels of the CB1 R m RNA in myocardial.There was a significant negatively correlation between the levels of the GLUT4 m RNA and CB1 Rm RNA in myocardial.IH may influence the CB1 R expression.Consequently,the expression of GLUT4 was affected.Finally,it can inhibit the signal transduction pathways of insulin in myocardial and cause the IR. Secondly Rimonabant treatment can improve IH-induced cardiomyocytes.Likewise, Rimonabant treatment also can upregulate the expression of GLUT4 and improve myocardial glucose metabolism, and then protect the myocardium. Simultaneously,Rimonabant treatment can improve IH-induced hyperinsulinemia and IR.