Sini Decoction Improves Myocardial Hypertrophy By Regulating TLR4/NF-κB Pathway

To observe the intervention effect of Sini Decoction on isoproterenol(ISO)-induced myocardial hypertrophy in rats and to explore its possible mechanism from the perspective of inflammation.Methods36 male SD rats were randomly divided into CON group,ISO group,CAP group and SND group,with 9 rats in each group.In addition to CON subcutaneous injection of saline,the other three groups were subcutaneously injected with ISO 5 mg/(kg·d)and for 1 week to replicate cardiac hypertrophy model.CAP group given 0.1g/(kg·d)captopril,2m L/only gavage;SND group given 3.8g/(kg·d)Sini Decoction,2m L /only gavage,Continuous gavage for 4 weeks,CON group and ISO group given distilled water 2m L/only gavage.After administration,The hemodynamics of the rats were measured after weighing(BW),the total heart weight(HW)and left ventricular weight(LVW)were weighed and calculate the Whole Heart Weight Index(HWI)and Left Ventricular Weight Index(LVWI).Hematoxylin-eosin(HE)staining was used to observe the degree of myocardial hypertrophy and the diameter and cross-sectional area of myocardial cells.Masson showed reduced proliferation of collagen fibers,while also reducing the volume fraction of collagen measured.Serum levels of TNF-α and IL-6 were detected by ELISA.Western blot was used to detect the expressions of TLR4,IκBα and Nuclear factor kappa B subunit p65(NF-κB p65)protein expression in the nucleus.TLR4 m RNA and Cardiac hypertrophy marker gene atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)m RNA expression was detected by QRT-PCR.ResultsCompared with the CON group,the cardiac systolic function and heart function of the rats in the ISO group were decreased;HW,LVW,HWI and LVWI were all increased(P<0.01).Myocardial cell hypertrophy and measurements of the cross-nuclear diameter and cross-sectional area of myocardial cells in the left ventricle increased significantly(P<0.01).collagen fibers proliferation and measured collagen volume fraction(CVF)increased(P<0.01).TNF-alpha,IL-6 in serum and expression of TLR4,NF-κB p65,ANP,BNP was up-regulated and I κ B α protein expression was down-regulated in cardiac tissue(P<0.01).Compared with ISO group,The SND group and the CAP group relieved cardiac function impairment caused by ISO;HW,LVW,HWI and LVWI were all decreased(P<0.01);cardiac myocyte hypertrophy was relieved while myocardial cell cross-nucleus diameter and cross-sectional area were also decreased(P<0.01);Reduction of collagen fibrosis and decrease of CVF value(P<0.01);TNF-alpha,IL-6 in serum and expression of TLR4,NF-κB p65,ANP,BNP decreased and I κ B α protein expression increased in cardiac tissue(P<0.01).ConclusionSini decoction can effectively improve isoprenaline-induced pathological myocardial hypertrophy,and its mechanism may be related to the inhibition of TLR4 / NF-κB inflammatory signaling pathway,down-regulation of inflammatory cytokines and reduction of collagen deposition.