ABSTRACT
Objective To investigate the effect of Shensong Yangxin capsule on cardiac remodelling of myocardial infarction mouse model and the possible molecular mechanisms. Methods Adult male C57BL/6J mice were divided into sham operation group(n=10), model control group(n=20)and Shensong Yangxin group(n=20)according to random number table. Left anterior descending branch of coronary artery was ligated to establish myocardic infarction model in the model control group and Shensong Yangxin group. From the 2nd day after the surgery, Shensong Yangxin ( 400 mg . kg-1 ) was intragastrically administered, and the death rate of the mice was observed.Four weeks after the surgery, echocardiography was used to measure the cardiac function;myocardiac infarction area was detected by pathological staining;the expression levels of cardiac remodelling markers and extracellular matrix proteins were detected by RT-PCR. The possible molecular mechanisms were screened by Western blotting. Results As compared with the model control group, Shensong Yangxin significantly reduced the mortality after myocardial infarction in mice(P<0.05), as well as the myocardial infarct size(P<0.05).The mRNA expression levels of cardiac remodelling markers ANP, BNP, and β-MHC and the extracellular matrix proteins(collagenⅠ, collagen Ⅲ, CTGF, TGFβ) decreased significantly in the Shensong Yangxin group as compared with the model control group. Western blotting showed that Shensong Yangxin significantly decreased activation of smad3, and reduced expression level of smad4. Conclusion Shensong Yangxin attenuates cardiac remodelling after myocardial infarction and the mechanism may be related with blockage of smad signaling pathway.
ABSTRACT
La geometría ventricular izquierda, determinada por ecocardiografía bidimensional, proporciona de manera indirecta información sobre el perfil hemodinámico y neurohormonal del paciente hipertenso. En dos estudios pilotos, llevados a cabo en el Instituto de Investigaciones Cardiovasculares de la Universidad de Los Andes hemos utilizado al patrón geométrico como guía para orientar el tratamiento farmacológico del paciente hipertenso. La correspondencia de la estrategia farmacológica con el mecanismo neurohormonal, responsable de la hipertensión arterial, permite un control de la presión arterial con menor número de medicamentos y reduce la incidencia de efectos colaterales y complicaciones. Más aún, el proceso de remodelación cardiaca puede ser influenciado favorable o desfavorablemente, si la estrategia terapéutica empleada se corresponde o no con el mecanismo neurohormonal subyacente. El proceso de remodelación cardiaca, en la transición hacia los dos fenotipos de insuficiencia cardiaca congestiva, se caracteriza por modificaciones opuestas de la geometría y función ventricular. Los pacientes que evolucionan hacia la insuficiencia cardiaca sistólica experimentan una progresiva dilatación de las cavidades cardiacas izquierdas y disminución de la función sistólica. Por el contrario, en los pacientes que evolucionan hacia la insuficiencia cardiaca diastólica, el tamaño de las cavidades cardiacas se reduce y la relajación ventricular se altera.
The neurohormonal and hemodynamic profiles, of uncomplicated hypertensive patients, can be inferred from the left ventricular geometric pattern. We have used the left ventricular geometric pattern to guide the pharmacological treatment of hypertensive patients. Blood pressure control can be achieved with less medications and complications and adverse effects are reduced with a therapeutic strategy aimed at the underlying neurohormonal and hemodynamic profiles. On the contrary, cardiac remodelling is unfavorably influenced by a therapeutic strategy unmatched to the underlying responsable mechanisms. During transition to the two phenotypes of congestive heart failure, cardiac remodelling evolves in opposite directions. Thus, patients with systolic heart failure undergo progressive ventricular dilatation with thinning of its walls, where as, diastolic heart failure patients are characterized by shrinking of their left ventricular cavities with increasing relative wall thickness.