RESUMO
OBJECTIVE: To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). MATERIALS AND METHODS: AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-ß1 (TGF-ß1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. RESULTS: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-ß1. CONCLUSION: SXND may antagonize the renin-angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-ß1.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Receptor Tipo 1 de Angiotensina/genética , Insuficiência Renal Crônica/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Western Blotting , Medicamentos de Ervas Chinesas/administração & dosagem , Eletrocardiografia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/patologia , Miocárdio/ultraestrutura , Insuficiência Renal Crônica/complicações , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVE: To investigate the expression pattern of adapter protein with a Src-homology 2 domain (SH2B1), the suppressor of cytokine signaling-3 (SOCS3), protein-tyrosine phosphatase 1B (PTP1B) and neturopetide Y (NPY) in obese and normal mice hypothalamus and its relation with serum leptin and insulin levels. METHODS: The obesity animal model was prepared with healthy C57/bl6 mice. Lee's index and Homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. The mRNA levels of SH2B1, SOCS3, PTP1B and NPY were measured by fluorescent quantitation RT-PCR. The SH2B1 and NPY protein expressions were detected by Western blot. RESULTS: Compared with the normal mice of the same age, SH2B1 mRNA expression in the obese mice hypothalamus decreased. SOCS3 and PTP1B mRNA expression increased. Western blot showed that SH2B1 protein expression decreased, while NPY protein expression increased in the obese mice. Linear correlation analysis showed that the serum leptin and fasting insulin levels were negatively correlated with SH2B1mRNA expression and positively correlated with SOCS3 and PTP1B mRNA expression. CONCLUSION: SH2B1, SOCS3, PTP1B and NPY are key factors for obesity development.