Protective Effect Of Xin-Ji-Er-Kang On Cardiovascular Remodeling In High-Saltinduced Hypertensive Mice

Background:Xin-Ji-Er-Kang(XJEK)is a traditional Chinese herbal medicine compound made from fourteen herbal medicines,including Panax ginseng,Ophiopogon japonicus,Astragalus mongholicus Bunge,and Polygonatum odoratum.Clinical and basic research have shown that XJEK has a certain protective effect on cardiovascular diseases such as myocardial infarction,coronary heart disease and myocarditis.Objectives:The aim of this study was to investigate the protective effect of XJEK on cardiovascular remodeling in hypersaline hypertensive mice and its possible mechanism.Methods:Sixty male Kunming mice were randomized into six groups,namely the Control,Model,Low-dose XJEK,Middle-dose XJEK,High-dose XJEK and Fosinopril groups(n=10 per group).In addition to the control group,the other five groups were given 8%high-salt diet for a total of 8 weeks,while the control group was fed ordinary diet.An additional 4,8 and 12g/kg/day XJEK were intragastrically administered to the Low-dose,Middle-dose and High-dose XJEK groups,respectively,and 2 mg/kg/day fosinopril to the fosinopril group,the control group and model group were given superpure water by gavage.In the experiment,the systolic blood pressure(SBP)of mice was measured weekly through the non-invasive blood pressure measurement analysis system.After 8 weeks,the changes in cardiac function and hemodynamics of the mice were analyzed by carotid artery intubation method,and the heart weight/body weight(HW/BW)was calculated.Hematoxylin and eosin(HE),Masson stain and collagen fibers(VG)were stained to observe the pathological changes of the heart and thoracic aorta.In vitro vascular ring experiment was performed to observe endothelial diastolic function.Serum nitric oxide(NO),malondialdehyde(MDA)and superoxide dismutase(SOD)were determined by colorimetry.serum angiotensin II(Ang II),aldosterone(ALD),n-terminal pronatriuretic peptide(NT-pro BNP),endothelin-1,endothelial NO synthase(e NOS),tumor necrosis factor-a(TNF-?),interleukin 1?(IL-1?),interleukin10(IL-10),asymmetric dimethylarginine(ADMA),tetrahydrobiopterin(BH4)concentration and L-arginine(determined by enzyme-linked immunosorbent assay).Western blot(WB)method was used to detect the expression of total e NOS,endothelin receptor A(ET_A),Nuclear factor-?B(NF-?B)protein p-p65/p65,TNF-?,IL-1?,IL-10protein in cardiac tissue.The distribution of e NOS in myocardial tissue was analyzed by immunofluorescence.Results:The statistical results showed that after 8 weeks of experiment,the systolic blood pressure(SBP)of the model group was significantly higher than that of the control group.Compared with the model group,the SBP of the XJEK dose group was significantly reduced,and it was associated with fosinopril.There was no significant difference in the drug treatment group.Pathological staining and heart weight/body weight(HW/BW)results showed that after 8 weeks of modeling,there was significant cardiovascular remodeling in the model group,and XJEK and fosinopril treatment could partially reverse cardiovascular remodeling.Results of hemodynamics and cardiac function showed that XJEK drug treatment could improve cardiac systolic and diastolic functions and hemodynamic parameters.He colorimetric results showed that compared with the model group,XJEK could up-regulate serum NO content,down-regulate MDA content and improve SOD activity(P<0.05).XJEK improves the bioavailability of L-Arg by promoting e NOS activity,increasing the expression of BH4,reduce ALD and NT-pro BNP content,reducing the contents of ET_A,ET-1 and ADMA in heart tissue(P<0.05),improving cardiac pathological changes,and improving the level of endothelial dysfunction(ED)and oxidative stress(OS).Compared with the model group,the p-p65/p65 ratio of inflammatory protein was significantly reduced,and the levels of TNF-?and IL-1?were significantly reduced after treatment in each dose of XJEK.The content of IL-10 in serum and myocardial tissue was significantly increased(P<0.05).Fosinopril had a similar effect.Conclusion:In conclusion,XJEK mitigates cardiac remodeling in high-salt-inducedhypertensive mice.The potential mechanism involves improved oxidative stress,endothelial dysfunction and reduceing inflammatory response,independently of ameliorating blood pressure(BP).