| Objective:To observe the effect of the aqueous extract (AECP) and flavonoids (FCP) from Cyclocarya paliurus on hypertensive rats induced by Nco-nitro-L-arginine methyl ester hydrochloride(L-NAME) and spontaneously hypertensive rats (SHR), then to explore its mechanism.Methods:1.Water extraction and ethanol extraction were used to prepare AECP and FCP, and experimental study of acute toxicity was done.2. Using L-NAME-induced hypertensive rats and rat tail artery pulse manometry, normal SD rats were used as the blank group (Control), and hypertensive rats were randomly divided into model group (Model), aqueous extract of Cyclocarya paliurus high (AECP-H), medium (AECP-M), low dose group (AECP-L) and captopril group (Captopril). Observe the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on rats after continuous AECP administration for6w; detect the NO content in serum, and observe the influence of the AECP on left ventricular mass index, kidney and thoracic aorta.3. Using SHR and rat tail artery pulse manometry, normal Wistar rats were used as the blank group (Control), SHR were randomly divided into model group (Model), FCP group (FCP), AECP high (AECP-H), medium (AECP-M), low dose group (AECP-L) and captopril group (Captopril). Observe the effect of SBP, DBP, heart rate (HR, Heart Rate), body weight and organ index after continuous AECP and FCP administration of9w and withdrawal lw.Retain Specimens from blood, serum, plasma and renal tissue, then determine the blood and the T-SOD, MDA, GSH-PX, NO, TNOS and ANP content. Observe SHR kidney HE staining pathological changes, electron microscopic examination of glomeruli, immunohistochemical expression of Ki-67and VEGF in the kidney, while observe histological changes of the left ventricle, aorta and renal artery.Results:1. The maximum tolerated crude drug dose of AECP and FCP on acute toxicity were:83.32g·Kg-1BW,66.45g·Kg-1BW, the mouse maximum tolerated multiple were:231times,184times. It is indicated safe when the amount is100times more than human.2. The blood pressure of L-NAME-induced hypertensive rats was significantly higher than the Control group, and blood pressure can be maintained at a high level, which can be used to do experimental study of lowering blood pressure.①Compared with the Model group, Captopril group and AECP groups can reduce SBP and DBP, the decreased rates were2.34%～16.92%,2.61%～16.64%, P<0.05or P<0.01. The antihypertensive effects of Captopril group were superior to the Cyclocarya paliurus group.②Compared with the Model group, Captopril group and AECP groups can increase NO content in serum.③Compared with the Model group, Captopril group and AECP groups can reduce hypertensive rats LVW/BW, and increase KW/BW. Kidneys of Model group under the light microscope showed the majority of glomeruli atrophy with fibrosis, the thickness of thoracic aortic artery wall varied, intima was of severe hyperplasia, and proliferation of medial smooth muscle cell, Captopril and AECP groups had been reduced.3. The SHR blood pressure was significantly higher than the Control group, which can be used to step-down experimental study.①Compared with Model group, Captopril, AECP and FCP group can reduce SBP and DBP, and the decreased rates were2.20%～14.29%,6.56%～11.89%, P<0.05or P<0.01. HR of rats in each group has no significant difference (P>0.05).The antihypertensive effects of Captopril group are superior to the Cyclocarya paliurus group.②The SW/BW, KW/BW, the PLT, GSH-PX NO, TNOS and ANP of Model group are significantly lower than the Control group, along with the drop in blood pressure, Captopril, AECP and FCP group can increase the SW/BW, KW/BW, GSH-PX, NO, TNOS content, reduce the content of ANP, and have no obvious effect on the PLT. The LVW/BW, RBC, HGB of Model group was significantly increased than the Control group. Captopril, AECP group and FCP group can reduce the LVW/BW and increase the RBC, HGB.③Kidneys of Model group under the light microscope showed some glomeruli atrophy with fibrosis, and electronic microscopy showed serious thickening and hyperplasia of the glomerular basement membrane, Captopril, AECP and FCP group can alleviate the symptoms. Immunohistochemical results showed higher positive expression rate of Ki-67and VEGF in the Model group, Captopril, AECP and FCP group was low.④In the Model group, myocardial cells and myocardial fibers were arranged in disorder, accompanied by edema, thickening, larger, fracture. Thoracic aortic intima was of severe hyperplasia, endothelial cell swelled and a small number was of rupture swelling, the medial smooth muscle cell proliferated. Glass-like lesions were found in the small arteries around the renal artery, accompanied by thickening of the small arteries. Captopril, AECP and FCP group can ease the symptoms.Conclusion:1. The acute toxicity test results showed that AECP and FCP were the safe herbs extracts.2. The AECP can lower the blood pressure of L-NAME-induced hypertensive rats, improve the content of NO in serum and the lesions of the heart, kidneys and the thoracic aorta.3. After continuous administration of AECP and FCP for9w, it can significantly lower SBP and DBP in SHR, but had no obvious effect on HR. It can alleviate the lesions of the left ventricle, kidneys, spleen and aorta, improve RBC, HGB, GSH-PX NO, TNOS content, and lower plasma ANP levels. The positive expression of Ki-67and VEGF in kidney was significantly inhibited, to some extent it had the role to reverse the SHR target organ damage. |
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