| Objective: To explore the effects of Xin Ji Er Kang on cardiovascular remodeling in 2K1 C induced hypertensive rats. Doing preliminary analysis of its mechanism in the two aspects of oxidative stress and endothelial function. And to compare the differences in pharmacology between each the polar parts of XJEK.Methods: The experiment of therapeutic effects of XJEK: 60 male SD rats were randomly divided into control group, model group, XJEK low dose group, middle dose group, high dose group and fosinopril group. Two kidney one clip(2K1C) method should be used in the latter five groups to establish renal hypertension model. Four weeks later, rats in the latter groups were treated by gavage administration of XJEK and fosinopril respectively for four consecutive weeks. Control group was given water. The changes of blood pressure was observed during the experiment. At the end of 8 weeks, the left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and the maximal rate of left ventricular pressure(±dp/dtmax) were measured. Then the hearts and thoracic aorta were removed to test some parameters. Cardiac index is calculated with heart weight/body weight(HW/BW). The top third of cardiac and thoracic aorta specimens were dye by hematoxylin and eosin(HE) and collagen fibers staining Van Gieson(VG)to observe the changes of morphology and fibrosis. The xanthine oxidase method, thiobarbituric acid method(TBA), nitrate reductase and serum samples alkaline hydrolysis methods were used to detect the level of superoxide dismutase(SOD), malondialdehyde(MDA), nitric oxide(NO) and hydroxyproline in myocardial tissue(Hyp). The content of angiotensinⅡ(AngⅡ) in serum was tested through radioimmunoassay. Western blot(WB) method was used to detect the levels of protein NOX2 in myocardial tissue.The experiment of therapeutic effects of each polar fraction of XJEK: 50 male SD rats were randomly divided into control group, model group, ethyl acetate extract of XJEK group, n-butyl alcohol extract of XJEK group, aqueous extract of XJEK group and fosinopril group. Two kidney one clip(2K1C) method should be used in the latter five groups to establish renal hypertension model. Four weeks later, rats in the latter groups were treated by gavage administration of each polarity components of XJEK and fosinopril respectively for four consecutive weeks. Control group was given water. The changes of blood pressure was observed during the experiment. At the end of 8 week, not only the relevant indicators above-mentioned should be tested, but also the content of BNP in serum was detected by double antibody sandwich enzyme-linked immunosorbent assay(ELISA) method.Results: The experiment of therapeutic effects of XJEK: After four weeks of intragastric administration, compared with the 2K1 C model group, the systolic blood pressure(SBP) and HW/BW of XJEK high dose group decreased significantly(P <0.01, P <0.05). LVSP, +dp/dtmax were descended significantly(P <0.01).Pathological indicators such as myocardial cross-sectional area(CSA), collagen volume fraction(CVF), perivascular collagen area(PVCA), the media thickness(MT) were significantly reduced(P <0.01). The level of Hyp in myocardial tissue was also significantly reduced(P <0.05). The content of SOD and NO in serum were significantly increased(P <0.01, P <0.05), while the level of MDA and Ang Ⅱwere significantly lower(P <0.01).The experiment of therapeutic effects of each polar fraction of XJEK: After four weeks of intragastric administration, compared with the 2K1 C model group, the SBP of ethyl acetate extract and n-butyl alcohol extract of XJEK groups was significantly lower(P<0.05), and LVSP,±dp/dtmax values decreased significantly(P <0.01, P <0.05). Pathological indicators of each polar fraction of XJEK groups such as CSA, PVCA, CVF were significantly reduced,M and M / L of n-butyl alcohol extract and aqueous extract of XJEK group were significantly reduced(P <0.01, P <0.05). Myocardial hydroxyproline content of three polar fractions group were significantly lower(P <0.01, P <0.05). NO, e NOS in serum were significantly increased(P <0.01, P <0.05), and the levels of MDA, AngⅡ, BNP were significantly lower(P <0.01).Conclusion: XJEK can significantly reduce the high blood induced by 2K1 C, improve cardiac remodeling and myocardial compliance. Also it can significantly improve endothelial function. Its effect may be related to the antioxidant properties of the compound and the increased concentrations of NO, or other. Further research also revealed that three polar fractions of XJEK have the antihypertensive effect, but the role of the mechanism is different which is related to the different active substance they have probably. |
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