Study On The Role Andmechanism Of VEGFR1 Receptor In Citronellal Inhibiting Diabetic Cardiomyopathy

BackgroundDiabetic cardiomyopathy refers to extensive focal necrosis of the myocardium caused by metabolic disorders and microvascular disease,subclinical cardiac function abnormalities,and eventually progress to heart failure（HF）.The pathophysiological changes of diabetic cardiomyopathy are characterized by myocardial fibrosis,left ventricular hypertrophy,decreased systolic function,and even heart failure.Citronellal（CT）(C₁₀H₁₈O,3,7-dimethyl-6-octenal)is an acyclic monoterpene aldehyde extracted from the plant citronella.Studies have shown that CT can improve atherosclerosis Sclerosis-induced endothelial dysfunction（ED）,and has antibacterial,anticonvulsant,antidepressant effects.Vascular Endothelial growth factor receptor 1（VEGFR1）is closely related to vascular permeability,extracellular matrix degeneration,vascular endothelial cell migration,proliferation,and angiogenesis.This study investigated whether CT can inhibit diabetic cardiomyopathy by down-regulating the expression of VEGFR1 by establishing a rat model of diabetic cardiomyopathy.Objective（1）To determine whether CT can improve diabetic cardiomyopathy.（2）To explore whether CT can improve diabetic cardiomyopathy by regulating the expression of VEGFR1.MethodSixty-six Sprague-Dawley（SD）male rats（aged 4 weeks,190±20g）were randomly divided into six groups:（1）Saline Group;（2）Diabetic Cardiomyopathy Group;（3）CT Control Group:Citronellal（150mg/kg/day）;（4）ZM306416 Control Group:（ZD64720.1mg/kg/day,gavage,ZM306416 is a VEGFR1 blocker）;（5）diabetic cardiomyopathy+CT Group:（Citronellal 150mg/kg/day）;（6）Diabetic Cardiomyopathy+CT+ZM306416 group:（Citronellal 150mg/kg/day,ZM3064160.1 mg/kg/day）.The diabetic cardiomyopathy rat model was established by feeding SD rats with high fat diet and intraperitoneal injection of Streptozocin（STZ）.At the same time,it was treated with CT（150mg/kg/day）and ZM306416,the following experiments were carried out:（1）observing the left ventricular myocardial fibers（LVFS）by ultrasound analysis of ejection fraction（EF）and left ventricular shortening（LVFS）;（2）observing the left ventricular myocardial fibers（LVFS）by hematoxylin-eosin（HE）staining;Reticular fibers were observed by silver staining,elastic fibers were observed by lichen red staining,and glycogen deposition was observed by periodic acid-schiff（PAS）staining;（3）the content of nitric oxide（NO）,Malondialdehyde（MDA）and the activity of superoxide dismutase（SOD）in Nitric Oxide,（4）Western blot（WB）,immunofluorescence（IHC）,immunofluorescence（IFC）and Western blot（WB）were used to detect the activities of superoxide dismutase（SOD）and superoxide dismutase（MDA）,and Quantitative Polymerase Chain Reaction Chain Reaction（Q-PCR）were used to down-regulate the expression of VEGFR1.Result（1）Through ultrasound analysis,we found that CT could improve the decrease of EF and LVFS in diabetic cardiomyopathy rats.（2）CT can improve myocardial structural abnormalities in diabetic rats by HE staining;Masson staining found that CT can improve myocardial fibrosis in diabetic rats;silver staining found that CT can improve reticular fiber deposition in the myocardium of diabetic rats;lichen red staining found that CT can improve elastic fiber deposition in the myocardium of diabetic rats;PAS staining found that CT can improve myocardial fibrosis in diabetic ratsGlycogen deposition.（3）Through the detection of oxidative indicators,we found that CT can improve the abnormal expression of oxidative indicators such as SOD,MDA,NO caused by diabetic cardiomyopathy.（4）Through immunohistochemistry,Western blot and immunofluorescence,it was found that CT may directly act on VRGFR1 and down-regulates the expression of VEGFR1.Conclusion（1）CT can improve diabetic cardiomyopathy;（2）CT acts directly on VEGFR1,thereby down-regulates the expression of VEGFR1,protecting the heart muscle and improving diabetic cardiomyopathy.