| Objectives:To investigate the effect of fasudil on the pyroptosis of myocardial cells in type 2 diabetic cardiomyopathy rats.Methods:Adult healthy male SD rats were selected and randomly divided into the Control group and the diabetes group,with 12 rats in each group.The Control group(Control group)was given a normal diet,and the model group(DM group)was given a high-fat diet.Rats in the DM group were given a single intraperitoneal injection of streptozotocin at 35 mg/kg after 7 weeks of high-fat diet,and their blood glucose was monitored at 1 day,3 days,1 week and 2 week after treatment.The blood glucose was stable within 4 weeks and higher than 11.1mmol/L,indicating the success of the diabetic rat model.High-fat feeding was continued to the successful model rats,and they were randomly divided into the model control group(DM Na Cl group)and fas hydrochloride group(DM fas group),6 rats in each group.Rats in the normal group were also randomly divided into the normal Control group(Control Na Cl group)and the fasudil hydrochloride group(Control fas group),with 6rats in each group.The drug group(fasudil hydrochloride group)was given Rho kinase inhibitor fasudil hydrochloride 10mg/kg/d intraperitoneal injection.Intraperitoneal injection was continued for 4 weeks,and the non-drug group(control group)was given the same volume of normal saline.To 8 weeks after the injection,the cardiac function of the rats was detected,and the occurrence of left ventricular diastolic dysfunction in diabetic rats suggested the onset of DCM.At 16 weeks after the injection,the cardiac structure and function of the rats were detected.The heart tissue of the diabetic rats showed myocardial interstitial fibrosis and left ventricular hypertrophy,and left ventricular systolic and diastolic dysfunction,indicating that the DCM model had been successfully established.After the treatment was completed,the cardiac function of the rats was evaluated by ultrasonography,myocardial tissue was taken to observe the changes of myocardial ultrastructure under the electron microscope,lactate dehydrogenase release experiment and western blot to detect the expression of proteins related to pyroptosi.Results:1.Fasudil had no significant effect on blood glucose level in type 2diabetic rats(P>0.05);2.Fasudil can improve left ventricular systolic and diastolic function in type 2 diabetic rats(P<0.05);3.Fasudil can improve myocardial ultramicroscopic results in type 2diabetic rats;4.Compared with non-diabetic rats,LDH activity is increased in diabetic rats(P<0.05);5.Fasudil can inhibit the expression of NLRP3 protein and casepase-1,ASC,IL-1β,IL-18 proteins(P<0.05).Conclusions:Pyroptosi plays an important role in the occurrence and development of diabetic cardiomyopathy.Fasudil may inhibit the expression of caspase-1,ASC,IL-1β,IL-18 proteins by reducing the expression of NLRP3,so as to inhibit the pyroptosi of diabetic cardiomyopathy cells and improve cardiac function,thereby delaying the progress of DCM. |
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