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.
Highlights
Cardiovascular disease (CVD)-induced heart failure is the leading cause of mortality worldwide (Roth et al, 2015)
Western blot analysis, real time polymerase chain reaction (RT-PCR) and other methods were used to clarify the role of CTGF in cardiorenal interactions from the whole tissue and cell level
Buxin Yishen decoction (BXYS) treatment groups, regardless of the dose, showed significant increase in Ejection fraction (EF) and fractional shortening (FS) compared with the model group (P < 0.01, P < 0.05)
Summary
Cardiovascular disease (CVD)-induced heart failure is the leading cause of mortality worldwide (Roth et al, 2015). Among people with CVD-induced heart failure, about 40%–50% have chronic renal dysfunction, a situation known as cardiorenal syndrome (CRS) (McAlister et al, 2004; Van Deursen et al, 2014). Current treatment options for type 2 CRS include diuretics, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers, β-blockers, vasodilators, inotropic drugs, erythropoiesis-stimulating agents, vasopressin receptor 2 antagonists, and dialysis (Naranjo et al, 2017). Many of these drugs target heart failure (HF) and can worsen renal function. Identifying novel mechanisms in the pathophysiology of type 2 CRS, as well as a therapeutic strategy, remain major challenges in clinical practice
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