| Section I Clinical researchObjectives:To investigate the clinical effect of nourishing yin and liver and promoting blood flow method in the treatment of hypertensive LVH.Methods:72cases of patients with left ventricular hypertrophy in essential hypertensive patients were randomly divided into experimental group (36cases) and control group (36cases), the experimental group was given oral compound Gouteng antihypertensive tablets used to nourish yin and liver and remove blood stasis, while the control group was given oral Telmisartan Tablets,24weeks as1course of treatment for both groups, a total of1course to observe the blood pressure, heart rate, TCM syndrome scoring, echocardiography IVST, LVPWT, LVDd, LVM, LVMI; E/A, IVRT, EDT indicators, and detect plasma high-sensitivity C-reactive protein, tumor necrosis factor a,interleukin-1β, interleukin-10,soluble vascular cell adhesion molecule-1.Results:(1) After treatment for24weeks, the total effective rate of observation group was83.33%, total effective rate of the control group was86.11%. the antihypertensive effect of the observation group and the control group had no significant difference (P>0.05), the blood pressure and heart rate levels of patients in two groups were significantly decreased after24weeks of treatment, compared with those before treatment, the difference was statistically significant (P<0.01,P<0.05),but there were no statistically significant difference between two groups after treatment (P>0.05);(2) the total effective rate of the treatment of TCM was72.22%in the observation group, the control group was52.78%. The total effective rate in observation group was higher than that in control group, the difference was statistically significant (P<0.05);(3)Comparing with the LVH of two groups, IVST, LVPWT, LVMI of observation group after treatment were significantly decreased than before treatment, and the LVMI of observation group was lower than the control group, the difference was statistically significant(P<0.05); there were no significant change of LVDd in two groups before and after treatment, and the difference showed no significance (P>0.05);(4)E/A, IVRT that were the index of left ventricular diastolic function in two groups were higher after treatment than pretreatment,E/A of observation group were higher than those in control group, there was a statistical significace (P<0.05);(5) plasma hs-CRP, TNF-α, sVCAM-1levels that were inflammatory cytokines in two groups were lower after treatment than pretreatment, the differences were statistically significant (P<0.05); after treatment of1L-1βlevel were significantly decreased than before treatment in control group, the differences were statistically significant (P<0.01); after treatment with the IL-10levels were elevated before treatment in two groups, the difference was statistically significant (P<0.05); But IL-10of two groups after treatment had no difference (P>0.05).Conclusions:compound Gouteng antihypertensive tablets used to nourish yin and liver and remove blood stasis can lower blood pressure and heart rate of LVH patients with Yin deficiency and yang hyperactivity, blood stasis syndrome, and improve the symptoms and signs of integral action, and can lower the levels of inflammatory cytokine. Section Ⅱ Experimental researchObjectives:To investigate the mechanism of nourishing yin and liver and promoting blood flow method in the treatment of hypertensive LVH that based on action of inflammatory cytokines network steady state mediated by the P38, TLR4signaling pathway.Methods:the establishment of SHR left ventricular hypertrophy model, were randomly divided into blank group, SHR compound Gouteng antihypertensive tablets group, telmisartan group, and WKY group, monitoring blood pressure and heart rate of the rats,plasma level of angiotensinⅡ, aldosterone, endothelin-1, serum high-sensitivity C-reactive protein, interleukin-1β, interleukin-10, tumor necrosis factor-alpha content by taking Elisa method;carrying protein-genetic level to detect inflammatory cytokine network mediated by the P38, TLR4signaling pathway.Results:(1)Blood pressure:After administration for4,8and12weeks, WKY group, compound Gouteng antihypertensive tablets group, rhynchophylline telmisartan group were lower than SHR blank group, there was a statistically significant difference (P<0.01, P<0.05); blood pressure of compound Gouteng antihypertensive tablets group and elmisartan group were decreased significantly compared with before administration, the difference was statistically significant (P<0.01);but the difference of blood pressure between compound Gouteng antihypertensive tablets group and telmisartan group were no statistically significant (P>0.05). (2)Heart rate:the heart rate of SHR blank group was increased significantly than before administration (P<0.01); the heart rate was decreased significantly than before administration in compound Gouteng antihypertensive tablets group and telmisartan group on8and12weeks, the heart rate of compound Gouteng antihypertensive tablets group were lower than those in telmisartan group on12weeks (P<0.05).(3)Levels of plasma inflammatory cytokines:After treatment for12weeks comparison of plasmaHs-CRP, IL-1β, TNF-αof all groups,the plasmaHs-CRP, IL-1β, TNF-α of WKY group,compound Gouteng antihypertensive tablets group and telmisartan group were lower than those in SHR blank group, the difference was statistically significant(P<0.01); and the plasma IL-10of WKY group,compound Gouteng antihypertensive tablets group and telmisartan group were higher than those in SHR blank group, the difference was statistically significant(P<0.01).(4)Index of left ventricular hypertrophy:compared with SHR blank group,the left ventricular weight (LVM) of compound Gouteng antihypertensive tablets group and telmisartan group decreased, the difference was statistically significant (P<0.05); the left ventricular mass index (LVMI) of compound Gouteng antihypertensive tablets group were lower than SHR blank group and telmisartan group, the difference was statistically significant (P<0.05); compared with SHR blank group, the left ventricular wall thickness of WKY group, compound Gouteng antihypertensive tablets group and telmisartan group decreased, the difference was statistically significant (P<0.01).(5)HE staining: there were a few inflammatory cells infiltrating cardiomyocytes in WKY group; myocardial cells of SHR control group were diffuse hypertrophy, deformity, and large nucleus, deeply stained, myocardial fibers edema, disorganized, and inflammatory cell infiltration obviously; myocardial cells hypertrophy mildly, muscle fibers arranged in neat and less inflammatory cell infiltration in compound Gouteng antihypertensive tablets group; in telmisartan group, myocardial cells edema, myocardial fibers arranged in disorder, inflammatory cell infiltration slight improvement compared with those in SHR blank group.(6)Masson staining:there was no hyperplasia of myocardial interstitial collagen in WKY group;A portion of myocardial fiber was necrotic and myocardial interstitial collagen was hyperplastic significantly in SHR control group; There was mild hyperplasia of myocardial interstitial collagen in compound Gouteng antihypertensive tablets group; muscle fibers of telmisartan group was in neat and myocardial interstitial collagen proliferated slightly.(7)Immunohistochemistry was used to detect rat cardiomyocytes and protein stereological image analysis and comparison of integrated optical density:①p38MAPK: compared with the SHR blank group, compound Gouteng antihypertensive tablets group and the telmisartan group were significantly lower with a statistically significance (P<0.01); p38MAPK of compound Gouteng antihypertensive tablets group were significantly lower than those in telmisartan group, the difference was statistically significant (P<0.05);②c-fos:,there were significantly lower in compound Gouteng antihypertensive tablets group and telmisartan group compared with SHR blank group, and the difference was statistically significant (P<0.01);③TNF-α:there were significantly lower in compound Gouteng antihypertensive tablets group and telmisartan group compared with SHR blank group, and the difference was statistically significant (P<0.05);④IL-1: compared with the SHR blank group, compound Gouteng antihypertensive tablets group and the telmisartan group were significantly lower with a statistically significce(P<0.01); IL-1of compound Gouteng antihypertensive tablets group were significantly lower than those in telmisartan group, the difference was statistically significant (P<0.05);⑤IL-10:there were significantly increasing in compound Gouteng antihypertensive tablets group and telmisartan group compared with SHR blank group, and the difference were statistically significant (P<0.01);⑥LR4: compared with the SHR blank group, compound Gouteng antihypertensive tablets group and the telmisartan group were significantly lower with a statistically significant (P<0.01); TLR4of compound Gouteng antihypertensive tablets group were significantly lower than those in telmisartan group, the difference was statistically significant (P<0.05);⑦NF-κB:ompared with the SHR blank group, compound Gouteng antihypertensive tablets group and the telmisartan group were significantly lower with a statistically significance (P <0.01). (8)Western-BIot testing:①omparing with the results of p38MAPK semi-quantitative testing, compound Gouteng antihypertensive tablets group were lower than the SHR blank group and telmisartan group, the difference was statistically significant (P<0.05);②omparing with the results of TNF-a semi-quantitative testing, compound Gouteng antihypertensive tablets group and telmisartan group were lower than the SHR blank group, the difference was statistically significant (P<0.05);③omparing with the results of IL-1βsemi-quantitative testing, compound Gouteng antihypertensive tablets group and telmisartan group were lower than the SHR blank group, the difference was statistically significant (P<0.01); the results of IL-1βsemi-quantitative testing in compound Gouteng antihypertensive tablets group were significantly lower than those in telmisartan group, the difference was statistically significant (P<0.05);④omparing with the results of IL-10semi-quantitative testing, compound Gouteng antihypertensive tablets group and telmisartan group were higher than the SHR blank group, the difference was statistically significant (P<0.05);⑤comparing with the results of TLR4semi-quantitative testing, compound Gouteng antihypertensive tablets group was lower than the SHR blank group and telmisartan group, the difference was statistically significant (P<0.01,P<0.05);⑥omparing with the results of NF-κB semi-quantitative testing, compound Gouteng antihypertensive tablets group and telmisartan group were lower than the SHR blank group, the difference was statistically significant (P<0.01). Conclusions:(1) nourishing yin and liver, promoting blood circulation method can stabilize the blood pressure in SHR model;(2) compound Gouteng antihypertensive tablets used to nourish yin and liver and promote blood circulation can reverse left ventricular hypertrophy in a certain extent;(3) hypertensive ventricular hypertrophy may be related to inflammatory cytokine expression induced by P38, TLR4signaling pathway;(4)the mechanism of nourishing yin and liver and promoting blood circulation method for treating hypertensive ventricular hypertrophy may be:by regulating p38MAPK, TLR4signaling pathway to reduce the levels of IL-1(3, TNF-a proinflammatory cytokines and elevate the levels of IL-10anti-inflammatory cytokines, and inhibit of NF-κB expression, thereby that can reverse left ventricular hypertrophy.
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