Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

Abstract

This study aimed to investigate the therapeutic effect of traditional Chinese medicine-Buxin Yishen decoction (BXYS) on type 2 cardiorenal syndrome (CRS) caused by myocardial infarction and explore the possible mechanism BXYS works. A chronic heart failure (CHF) rat model induced by left anterior descending coronary artery ligation was used and five groups were created that included a sham group, a CHF model group, a fosinopril group, a BXYS (0.4 g/kg) group and a BXYS (0.8 g/kg) group. Heart function, renal hemodynamics, neuroendocrine factors, serum, and urine concentration of soluble form connective tissue growth factor (sCTGF), expression of CTGF mRNA, CTGF, α-smooth muscle actin (α-SMA), and low-density lipoprotein receptor-related protein (LRP) in renal tissues were evaluated after 28 days and 60 days of drug administration. Histological analysis of kidney tissues was also performed. In vitro experiments were designed to verify the results of in vivo experiments by detecting factors including CTGF, α-SMA, in NRK-52E cells. Rats with CHF showed obvious pathophysiological changes including: altered renal hemodynamic parameters; dysregulated heart function; changes to serum concentrations of angiotensin II (AngII), cyclic guanosine monophosphate (cGMP), serum creatinine (Scr), blood urea nitrogen (BUN), C-reactive protein (CRP), brain natriuretic peptide (BNP); high serum and urine sCTGF concentration; high CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues; increased extracellular matrix (ECM) deposition and fibrosis in renal tissues. Treatment of BXYS was correlated with a restoration of heart function and improvement of renal hemodynamics, lower serum and urine sCTGF, lower CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues and lower ECM deposition. In addition, in vitro experiments showed that treatment with BXYS reduced the α-SMA and LRP concentration in NRK-52E cells, which were similar in vivo experiments. In conclusion, the current study provided evidences that BXYS played a role in improving heart function and delaying the progress of renal fibrosis. Meanwhile, the CTGF-LRP pathway might be one of the therapeutic targets for myocardial infarction caused type 2 CRS which showed a positive change after BXYS treatment and is worthy of further exploration.

GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation

“…The cardiac characteristics observed in this study are consistent with previous reports using this model of HF [41][42][43]. Additionally, substantial number of previous studies [44][45][46][47][48][49][50][51] demonstrated that natriuretic peptide levels in both the heart and the serum are significantly increased in rats with HF induced by coronary artery ligation used in the current study. Taken together, the ˃ 30% infarct size, increased LVEDP, LVEDD, LVESD, LVEDV and LVESV and decreased dP/dt, FS, EF, SV and CO all indicate that rats in HF group were experiencing cardiac dysfunction.…”

Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome

“…Increased cardiac fibrosis is associated with augmented myocardial stiffness, cardiomyocyte necrosis, arrhythmias, sudden cardiac death and unfavorable prognosis, and plays an important role in the remodeling process that leads to HF ( Espeland et al, 2018 ). Increased renal fibrosis is a key contributor to the progressive decline in renal function with time ( Hewitson, 2009 ; Qiu et al, 2019 ). Consistent with previous studies ( Liu et al, 2013 ; Savira et al, 2020b ), VEH-treated MI + STNx rats had significant increases in cardiac and renal interstitial fibrosis and myocyte hypertrophy, which were associated with upregulation in gene expression of key pro-hypertrophic and pro-fibrotic markers.…”

Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2

“…It is well recognized that renal fibrosis caused by chronic heart failure is an important pathological feature of CRS2, which could develop into end-stage renal disease. 7 Heat shock protein 90 (HSP90) is one of the most abundant molecular chaperone proteins and is involved in cell survival, growth, and differentiation. 8,9 HSP90 has been reported to be activated in many fibrotic diseases, for example cardiac fibrosis, 10 renal fibrosis, 9 and pulmonary fibrosis.…”