Mechanism of Qiangxin Decoction protecting cardiovascular endothelium in the treatment of chronic heart failure.

Objective To investigate the mechanism of Qiangxin Decoction treating chronic heart failure(CHF) by regulating miR-125b-5p and thus inhibiting the expression of nuclear factor-κB (NF-κB)-mediated inflammatory factors in order to protect the cardiovascular endothelial progenitor cells. Methods According to the random number table method, 42 SPF-grade SD rats were divided into the control group, the model group, the Qiangxin Decoction low-dose group (7.45 g/kg), the Qiangxin Decoction medium-dose group (14.90 g/kg), the Qiangxin Decoction high-dose group (29.80 g/kg), and the sacubitril valsartan group (10.42 mg/kg), with 7 rats in each group. Except for the control group, the CHF model was established by ligating the left anterior descending branch of the coronary artery in each group. Two days after modeling, the rats were treated with the corresponding drugs by gavage for 28 days. Cardiac function indexes, including left ventricular end-diastolic internal diameter (LVEDd), left ventricular end-systolic internal diameters (LVEDs), and left ventricular ejection fraction (LVEF), were examined by cardiac ultrasound examination, and the pathological changes in the myocardial tissue of the left ventricle of the rats were observed by HE staining. Myocardial fibrosis was observed in each group by Masson staining. Fluorescence in situ hybridization (FISH) was performed to determine the expression of miR-125b-5p in endothelial progenitor cells of the left ventricular myocardial tissue. The protein expressions of brain-derived neurotrophic factor (BDNF), NF-κB p65 and p-NF-κB p65 in the left ventricular myocardial tissue were detected by Western blotting. Enzyme-linked immunosorbent assay was used to detect the expression of inflammatory factor tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Results Compared with the control group, LVEDd and LVEDs were elevated and LVEF was reduced in the model group; the pathological damage of myocardial tissue was severe with abnormal changes in the tissue structure, striated muscle became fuzzy, and cardiomyocytes were disordered in their arrangement and partially denatured and necrotic; blue collagen fibers and mucus deposition in the myocardial tissues were increased; the average optical density of miR-125b-5p was increased in the left ventricular myocardial tissue; the protein expression of BDNF was decreased, and the ratio of p-NF-κB p65/NF-κB p65 was increased; the contents of TNF-α, IL-1β, and IL-6 were significantly increased (P<0.05). Compared with the model group, LVEDd and LVEDs were reduced, and LVEF was increased in the Qiangxin Decoction medium-, high-dose groups and the sacubitril valsartan group; the pathological damage of myocardial tissues in the left ventricle was improved, with clear striated muscle, neat and orderly arrangement of cardiomyocytes, and reduction of cellular necrosis; blue collagen fibers and mucus deposition were reduced, and myocardial fibrosis was significantly reduced; the average optical density of miR-125b-5p in the left ventricular myocardial tissue was significantly reduced; the protein expression of BDNF was increased, and the ratio of p-NF-κB p65/NF-κB p65 was reduced; the contents of TNF-α, IL-1β, and IL-6 were significantly reduced (P<0.05). Conclusion Qiangxin Decoction can reduce miR-125b-5p expression, inhibit the activation of NF-κB pathway, reduce the expression of the pro-inflammatory factors TNF-α, IL-1β, and IL-6, attenuate the myocardial inflammatory response, pathological injury and reduce myocardial fibrosis, ultimately protect the cardiovascular endothelium, and improve cardiac function to treat CHF. [ABSTRACT FROM AUTHOR]