| Objective:To explore the protective effect on diabetic cardiomyopathy by ethanol extaction of Lycopus lucidus Turcz(ELT)and its possible mechanism might be related with regulation of PI3K/Akt/mTOR signaling pathway.Methods:60 SD male rats weighted 2001±20g were fed high fat diet for one month.The SD rats except the normal group(Control)were given intraperitoneal injection of streptozotocin(STZ)for 35 mg/kg.On the 3rd and 7th day,the fasting blood glucose of the rats was measured to be≥11.1mmol/L,which was the success of diabetes modeling.The rats were randomly divided into diabetic cardiomyopathy model group(DCM);high-dose group(ELTH,80mg/kg/d);medium-dose group(ELTM,40mg/kg/d);low-dose group(ELTL,20mg/kg/d);metform in group(MET,200mg/kg/d).The normal group was given a single intraperitoneal injection of equal volume of sodium citrate buffer(calculated according to the body weight of STZ injection volume).Blood glucose and body weight had been measured at a fixed time every week.SD rats in each group were fed with high-fat and high-sugar diet for 4 weeks,and then given gavage treatment for 8 weeks.In the end,each rat was weighed,anesthetized and fixed in turn.The hemodynamic changes of left ventricle were detected by PV-loop intubation,blood was collected,and the heart weight was recorded.Blood glucose,body weight and heart weight were measured;the maximum increase and decrease rate of left ventricular pressure(±dp/dt max),left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),cardiac output(CO);the changes of LDH,CK-MB,Insulin,ANP and BNP in serum were measured by ELISA kit;HE staining was observed the pathological changes of myocardium;Western blotting was observed the changes of protein expression of PI3K,p-PI3K,Akt,p-Akt,mTOR,p-mTOR,MMP-3,MMP-9 and HIF-la in cardiomyocytes.Result:1.Compared with the normal group,the heart-body ratio and blood glucose level in the DCM group increased significantly(P<0.05).Compared with the DCM group,the heart-body ratio of the ELTH group and the MET group decreased significantly,and the blood glucose level decreased significantly(P<0.05).However,there was no significant change in body-heart ratio and blood glucose level between the ELTM group and the ELTL group(P>0.05).2.OGTT results showed that compared with the normal group,the blood glucose level of the model group increased significantly at 0,30,60 and 120 min(P<0.05).Compared with the model group,the blood glucose level of 0,30,60 and 120 min in metformin group was significantly lower(P<0.05);the blood glucose level of 30,60 and 120 min in ELTH group was significantly lower(P<0.05);the blood glucose level at 60 and 120 min in ELTM group was significantly lower(P<0.05);the blood glucose level at 120 min in ELTL group was significantly lower(P<0.05).3.The detection result of PV-loop intubation showed that,compared with the normal group,the heart rate,cardiac output,the maximum rate of increase and decrease of left ventricular pressure,and the left ventricular systolic pressure in the DCM group significantly decreased(P<0.05),and the left ventricular end diastolic pressure(LVEDP)significantly increased(P<0.05).However,compared with the DCM group,the MET group and the ELTH group effectively improved the changes of the above indicators,especially the CO,±dp/dt max and LVSP values in ELTH group significantly increased,and the LVEDP values significantly decreased(P<0.05).4.ELISA results showed that compared with the normal group,the indicators of CK-MB,LDH,ANP and BNP in the DCM group were significantly increased(P<0.05),and the level of Insulin was significantly decreased(P<0.05).Compared with the DCM group,the changes of serological indicators such as CK-MB,LDH,ANP and BNP in the ELTH group were significantly reduced(P<0.05),and the level of Insulinindicators were significantly increased(P<0.05).The BNP index in the ELTM group was significantly reduced(P<0.05).The CK-MB and ANP indexes in the MET group decreased significantly,while the Insulin level increased significantly(P<0.05).5.HE staining results showed that compared with the normal group,the myocardial cells in the DCM group were disordered in arrangement,cells were enlarged,and the tissue structure and morphology were not clear enough.Compared with the DCM group,the myocardial cells in the ELTH group were arranged more regularly,and the tissue structure and morphology were also relatively complete.There was a slight difference in myocardial cell and histological integrity in the ELTM group.In the ELTL group,the arrangement of cardiomyocytes was irregular,the cells were enlarged,and the tissue structure and morphology were not clear enough.The cardiomyocytes in the MET group were arranged in a neat manner,with clear and complete tissue structure and morphology.6.Western Blot results showed that,compared with the normal group,the protein levels of p-PI3K,p-Akt and p-mTOR in the DCM group were significantly down-regulated,and the levels of HIF-la,MMP3 and MMP9 were significantly up-regulated(P<0.05).Compared with the DCM group,the protein levels of p-PI3K,p-Akt and p-mTOR in the ELTH group were significantly up-regulated,and the levels of HIF-la,MMP3 and MMP9 were significantly decreased(P<0.05).However,there was no significant difference between the ELTM group and the ELTL group.Conclusion:ELT can improve cardiac function and glucose metabollism disorder through anti-inflammatory and anti-oxidant stress.The mechanism might be related to the regulation of PI3K/Akt/mTOR signaling pathway. |
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