Protective Effects And Mechanisms Of Hawthorn Leaf Flavonoids On Diabetes Cardiomyopathy In Rats

Objectives: Rats of type2diabetic cardiomyopathy (DM) model were established bystreptozotocin(STZ) in this study, using hawthorn leaf flavonoids (HLF) therapeuticintervention, to observe its influence of myocardial morphology, inflammatory markersand oxidative indexes on myocardial tissue in DM model rats, and to explore theprotective effect and mechanisms of hawthorn leaf flavonoids on DCM in rats.Methods: Male sprague-dawley rats(n=80), which were randomly divided into normalcontrol group(n=10) and model group(n=70), after adaptive feeding for one week, thecontrol group were fed with normal diet for8weeks, the model group were fed withhigh sugar and high fat diet for8weeks. Then model group rats were injected with40mg/kg streptozotocin by intraperitoneal, blood glucose levels were tested after72h,fasting plasma glucose≥16.7mmol/L in rat was selected as a success DM model rat, hecontrol group were injected with an equal volume of citrate buffer, the successfulmodels were divided into four groups diabetic cardiomyopathy (DCM group), HLFlow dose group (HLF50mg/kg/d), HLF medium dose group (HLF100mg/kg/d), HLFhigh dose group (HLF200mg/kg/d), continuous administration for16weeks, fastingplasma glucose were tested. the hearts were separated and weighed, changes of cardiacindex was calculated. antioxidant index were detected, the concentration of TNF-α wasdetected with enzyme linked immunosorbent assay, the morphological changes ofmyocardial cells were observed by light microscope, the expression level of the PKC-αmRNA of diabetic myocardial was detected by RT-PCR. The expression level ofPKC-α and NF-κB of diabetic myocardial were detected by Western blot.Results:(1) Compared with the Control group,the body weight of DCM group ratswere reduced significantly(P <0.05), heart weight/body weight ratio of DCM grouprats were significantly increased (P <0.05), after treatment by HLF for16weeks, bodyweight and heart weight in rats/body weight ratio was significantly reduced (P<0.05).(2)The blood glucose of DCM group was significantly increased than thecontrol group, the blood glucose of HLF group were decreased than the DCM group, and there was a dose-dependent manner.(3)Compared with the control group, SODactivity of myocardial tissue in diabetic rats were decreased(P>0.05), the content ofMDA was increased significantly (P<0.05). SOD activity was up-regulated and thecontent of MDA was decreased by treatment with HLF (P<0.05).(4)The concentrationof TNF-α in diabetic rats was increased significantly compared with the control group(P<0.05), the concentration was decreased after treatment with HLF(P<0.05).(5)Compared with the normal group, myocardial structural abnormalities obviously indiabetic rats. this changes were improved after treated with HLF.(6)RT-PCR showedthat the expression of PKC-α mRNA was increased significantly in diabetic rats(P<0.05), the expression of PKC-α mRNA was decreased significantly after treatedwith HLF(P<0.05).(7)Western blot results showed that the protein expression ofPKC-α in membrane and NF-κB in nucler were increased significantly in diabetic rats(P<0.05), the protein expression of PKC-α in membrane and protein expression ofNF-κB in nuclear were decreased significantly after treatment with HLF(P<0.05).conclusions: HLF has a protective effect on diabetic cardiomyopathy rats. Themechanism may be involved in reducing the myocardial tissue of diabetic rats withinflammation and oxidative stress damage by inhibiting activation of PKC-α signalingpathways.