Study On The Cardioprotective Effect Of Velvet Antler Polypeptide On Ischemic Myocardial Injury In Rats With "Kidney Yang Deficiency Syndrome"

Objective:Establish a rat model of ischemic myocardial injury under "kidney yang deficiency",observe the protective effect of velvet polypeptide on the heart of rats with ischemic myocardial injury under kidney yang deficiency,and explore the relationship between velvet polypeptide repairing myocardial injury and "strengthening kidney yang and benefiting essence".The relationship between "blood" reveals its function of repairing heart-kidney disharmony and clarifies the relevant mechanism of action.Method:The experiment was divided into a blank group(Normal group),a model group(YD/MI group),a positive drug Youguiwan-Metoprolol tartrate group(YM group,500mg/kg+20mg/kg),antler polypeptide high-dose group(YD/MI+VAPH group,300mg/kg),medium-dose velvet polypeptide group(YD/MI+VAPM group,200mg/kg),low-dose velvet polypeptide group(YD/MI+VAPL group,100mg/kg).Except for the blank group,the rats in the other groups were given continuous intramuscular injection of hydrocortisone 25 mg/kg for 21 days and intraperitoneal injection of Adriamycin(Doxorubicin)2.2 mg/kg for modeling,followed by intragastric administration for 28 days.The detection indicators are as follows: observe the signs and states of the rats in each group;the Powerlab eight-channel biological signal acquisition and processing system detects the changes in the ST segment of the electrocardiogram of the rats in each group;Hematoxylineosinstaining,HE was used to detect the pathological changes of myocardial and renal tissue in rats in each group;to detect the changes of myocardial enzyme indicators CK-MB,LDH and kidney yang deficiency indicators SOD,MDA,cAMP,cGMP,cAMP/cGMP;Western Blot Methods The expression levels of microvascular injury-related factors HIF-1,VEGF and renal fibrosis-related factor TGF-β1 in kidney tissue were detected,and the protective effect of velvet antler polypeptide pretreatment on ischemic myocardial injury in rats with "kidney yang deficiency syndrome" was explored..Result:1.The general state of the rats in each group: the rats in the blank group have bright eyes,quick movements,thick hair,close to the body,normal food intake and excretion;in the model group rats,two eyes can be seen Apathy,lethargy,sluggishness,decreased activity endurance,decreased back temperature,cool and dark tail,dry,upright,easy to fall off fur,crouched and shrunken shoulders,huddled together,edema of the dorsum of feet,weight loss,loss of appetite,urine output Reduced,loose stools and other characteristic manifestations of heart and kidney yang deficiency.The general state of the rats in the positive drug group and the high-dose antler polypeptide group was close to the normal group;the general state of the rats in the low-dose antler polypeptide group and the middle-dose group was between the high-dose antler polypeptide group and the model group;Rats in each group had increased urine output to varying degrees,and their general states such as spirit,fur,back temperature,and diet were not significantly different from those in the positive drug group.It shows that deer antler polypeptide can significantly improve the general state of kidney-yang deficiency rats under ischemic myocardial injury.2.Electrocardiogram results: Compared with the Normal group,the ST segment of the descending branch of the rats in the YD/MI group was significantly elevated,suggesting that the rat MI model was successfully established.Compared with the YD/MI group,the level of ST-segment elevation in the YM group,YD/MI+VAPH,M,and L groups was significantly lower.3.Myocardial pathological changes: In the Normal group,the myocardial fibers were arranged in an orderly manner,with a clear structure and complete shape;after myocardial infarction,the myocardial fibers were arranged chaotically,with obvious fibrosis,many inflammatory cell infiltrations and enlarged intervals.In group YM,group YD/MI+VAPH,M,and L,the degree of invasion and fibrosis of cardiac tissue was significantly reduced,and there was a tendency to decrease significantly.4.Renal pathological changes: the renal capsule in the Normal group was intact,without hyperplasia of connective tissue,and without inflammatory response;in the cortex,the glomerulus had no obvious vascular proliferation and atrophic fibrosis,and no obvious degeneration and necrosis;There were no pool degeneration,hyaline degeneration,and necrotic changes in the tubules,and no tubular structures formed by cells and proteins were found in the medullary ring and collecting tubules;there was no hyperemia and infiltration of various inflammatory cells in the tissue;the renal pelvis endothelium The structure is intact,without degeneration,necrosis,and shedding.In YD/MI group,glomerular atrophy,hyalinization,thickening of basement membrane,stenosis or occlusion of lumen,tubule atrophy and fibrosis,epithelial cell swelling,proliferation and scar formation can be seen in the early stage of sclerosis.Glomerular atrophy and fibrosis in YM group,YD/MI+VAPH group,M group and L group were all alleviated compared with model group.5.Detection of serum,kidney yang deficiency,and myocardial related indicators:Compared with the Normal group,the activity of myocardial enzymes LDH and CK-MB in the YD/MI group was significantly increased(P<0.01);in the YM group,YD/MI+VAPH,M group and Compared with YD/MI group,the activities of myocardial enzymes LDH and CK-MB were significantly lower than those of YD/MI group(P<0.05,P<0.01);compared with Normal group,the contents of MDA and cGMP in YD/MI group were significantly increased.High,while the contents of SOD and cAMP decreased significantly(P<0.01).YM group and VAPH,M group were significantly lower than YD/MI group(P<0.05,P<0.01),and there were significant differences in serum SOD,MDA,cAMP,cGMP(P<0.05,P<0.01).Especially the value of cAMP/cGMP has a significant difference(P<0.01).6.Western Blot results: renal fibrosis-related factors: the expression level of TGF-β1protein in YD/MI group was higher than that in Normal group(P < 0.05).After administration,the expression of TGF-β1 protein in YM group and VAPH,M group was significantly lower than that in YD/MI group(P<0.05).Factors related to microvascular injury: Compared with the Normal group,the expression of HIF-1 protein in the YD/MI group was significantly increased(P < 0.01).Compared with the YD/MI group,the expression of HIF-1 protein in the YM group and VAPH,M,L groups decreased after administration(P<0.01).Compared with the Normal group,the expression of VEGF protein in the YD/MI group was significantly decreased(P<0.01).Compared with YD/MI group,the expression of VEGF protein in YM group and VAPH,M group increased after administration(P<0.01).Conclusion:1.Deer antler polypeptide can regulate the levels of multiple indicators(LDH,CK-MB,SOD,MDA,cAMP,cGMP,cAMP/cGMP)of ischemic myocardial injury under the syndrome of kidney yang deficiency.The mechanism of its therapeutic effect may be by increasing the content of SOD and cGMP in the serum of model rats with heart-kidney yang deficiency,and reducing the content of MDA and cAMP in serum,so as to reduce the accumulation of oxygen free radicals in the body,improve myocardial peroxidative damage,regulate Increase the concentration of ions inside and outside myocardial cells,prolong the action potential,and achieve the effect of resisting myocardial injury and kidney yang deficiency.2.Deer antler polypeptide delays the progression of renal interstitial fibrosis through the TGF-β1 signaling pathway,thereby protecting the myocardium.3.The velvet antler polypeptide may reduce the microvascular injury in the myocardial injury model rats with kidney yang deficiency through the HIF-1/VEGF signaling pathway.4.We have found through research that different doses of pilose antler peptides have a significant improvement effect on myocardial injury model rats under kidney yang deficiency,suggesting a dose-effect relationship,which can provide laboratory doses for its clinical application basis.