养心颗粒调控GSK3β、COX2和AQP2干预心衰大鼠水钠潴留的作用机制OA

To investigate the mechanism of Yangxin Granules in regulating GSK3β,COX2 and AQP2 to intervene in water-sodium retention in heart failure rats.Methods:One hundred SPF-grade SD rats were randomly divided into sham operation group(10 rats)and modeling group(90 rats).The modeling group underwent ligation of the left anterior descending coronary artery for 2 weeks to establish a post-myocardial infarction heart failure model.The modeling group was then randomly divided into model group,Yangxin Granules low-dose,medium-dose,and high-dose groups,tolvaptan group,and combined intervention group(tolvaptan+Yangxin Granules).All groups received once-daily drug interventions.Urine output was collected at 6,12,and 24 h during weeks 2 and 4 of treatment.After the final administration,cardiac ultrasound was performed to record left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS).Urine output and body weight were recorded,and heart and kidney indices were calculated.Serum brain natriuretic peptide(BNP)levels were measured by ELISA.Myocardial tissue pathology was observed via HE and Masson staining.Western blot was used to detect expression levels of GSK3β,COX2,and AQP2 proteins in renal tissues.Results:Compared with the model group,Yangxin Granules increased urine output(P<0.05),decreased serum BNP levels(P<0.05),improved cardiac function(LVEF and LVFS,P<0.05,P<0.01),and upregulated COX2 expression(P<0.05).Compared with the model group,the tolvaptan and combination groups showed downregulated GSK3β and AQP2 expression(P<0.01).Yangxin Granules alleviated myocardial tissue damage and inflammatory cell infiltration.Conclusion:Yangxin Granules can regulate renal tubular GSK3β and COX2 expression,thereby inhibiting AQP2,reducing water reabsorption,thus exerting therapeutic effects on water-sodium retention in heart failure.