The Effect Of Xuezhikang On The Process Of Essential Hypertension And Its Immunologic Mechanism

Objective Both heart and kidney are main impaired target organs in essential hypertension patients . Left ventricular configuration reflects the degree of ventricular remodeling and urine protein repesents the degree of impaired renal. The changes of ventricular configuration and diastolic function represent the ventricular remodeling directly or indirectly. Impaired regional diastolic function is the earliest clinical feature of ventricular remodeling and it is earlier than the changes of ventricular configuration. Microglobulin is a earlier change of impaired kidney.In this research we tried to investigate whether Xuezhikang increased the rate of the controlling of blood pressure , improved the ventricular remodeling, diastolic function and serum or urine microglobulin in patients with essential hypertension. The effect of xuezhikang on the serum levels of immune factor, oxidative stress and myocardial fibrosis, as well as the relationships between them were also observed. So as to make clear whether immune mechanism affect the process of hypertension and xuezhikang play a role in the course of hypertension.Method This was a randomized, single -blind , placebo-controlled study. 120 systemic hypertension (HT) patients with normal or lightly elevated cholesterol were randomized to assign to groups of placebo and Xuezhikang (1200 mg/d) for 24 weeks. Extended-released nifedipine were administrated to HT patients. 30 healthy volunteers served as controls. Plasma were obtained at baseline and after 24 weeks of Xuezhikang therapy. After 24 weeks treatment, 30 cases were selected from each group respectively to continue this study as before until the end of 72 weeks. Those parameters of diastolic function including Em/Am ratio at atrioventricular ring , E/A ratio at mitral orifice , IVSTd, LVIDd,LVPWTd and so on were measured by echocardiography. Circulatingimmune complexes (CIC) , immunoglobulins(Igs),C-reactive protein(CRP), malondialdehyde (MDA), superoxide dismutase photoinhibition rate (SOD-PR) and Type I collagen carboxypropeptide (PIP),microglobulins were determinedResults . 1. Left ventricular remodeling and diastolic function in HT patients: Comparing with the control group, LVWT, IVSTd, LVPWTd increased and LVIDd decreased in patients with hypertension (P =0.05). The incidence of Em /Am <1 and E /A <1 were higher than that of control group. The influencing factors on degree of impaired regional diastolic function were time (XI) and grades(X2) of hypertension(Y=0.63+0.59X1+0.53X2 ; F= 17.5, P <0.001). There was a relationship between E/A and Em/Am by gradual regressive analysis(E/A = 0.38JLAVL+0.59JLAVI+0.31JRAVI-0.22, F=16.7, P<0.001). Also a negative relationship between E /A and PIP was observed.After 24 weeks treatment, there were no significant differences in those parameters comparing that before treatment in xuezhikang group. Comparing with the placebo group, the Em/Am ratio increased at JLAVL (P<0.05), and the other parameters did not changed. After 48weeks and 72weeks treatment, the E/A ratio increased (P<0.05), but the parameters of left ventricular configuration did not changed significantly.2. The levels of plasma CRP, MDA, SOD-PR, PIP in HT patients: Comparing with the control group, those parameters were higher in HT patients. After 24 weeks treatment the levels of plasma CRP, MDA, PIP and SOD-PR were significant decreased in Xuezhikang group while these parameters were not changed in placebo group. There was a positive relationship between PIP and MDA.3. The levels of plasma α1MG,β2MG,CIC,Ig and urine α1MG, β2MG in HT patients: Comparing with the control group, those parameters were higher in HT patients. The levels of plasma CIC decreased from the end of 24 weeks to the end of 72 weeks. Comparing with the placebo group, the levels of total Ig(IgG+IgA+IgM) , α1MG, β2MG, IgG,CIC in plasma and Urine β2MGdecreased at the end of 72 weeks, but the difference of urine α1MG is not significance. The regression equations that obtained by Multiple regression analysis were α1MG(urine)=1.18CIC-0.383HDL+0.214(F=6.56,P=0.03),β2MG (urine) =0.31CIC+0.234TC-0.712HDL (F=5.19, P=0.03) respectively. The difference of urine α1MG =0.515 (the difference of CIC) +0.112 (the difference of TC), (F=6.383, P=0.04); The difference of urine β2MG =0.05 (the difference of CIC) +0.008 (The difference of TC) , (F=5.578, P=0.049) .4. The relationship between PIP and IgG or CIC,TC,LDL-C,MDA,CRP : There was a positive relationship between PIP and CIC . The regression equations were PIP=(5.862E-02)MDA+0.313CIC+0.29CRP-0.598 ( F=16.02, P=0.02 ) that obtained by Multiple regression analysis.Conclusion Ventricular remodeling and impaired diastolic function as well as microglobulin abnormality appeared in HT patients and xuezhikang exerts cooperativity in improving diastolic function and decreasing urine microglobulin via immunomodulation,controlling blood pressure ,relieving oxidation loading, and anti-inflammatory. There was a trends that the site of Regional impaired diastolic function was from right ventricular to left ventricular. Regional impaired diastolic function of right ventricular probably be the first clinical feature in HT patients. The entirety diastolic function of left ventricular was correlated with regional diastolic function.PIP was one of the factors that affects the regional diastolic function of left ventricular while PIP was correlated with CIC and MDA. Though Xuezhikang can not affect IVSd, LVPWd and LVIDd significantly, it can improve diastolic function in HT patients after using it. Moreover xuezhikang might play an important role in lowering plasma and urine microglobulins via immune mechanism,specially via decreasing CIC and TC.