心肌尔康多糖对L-NAME诱导高血压小鼠心血管重构的保护作用

发布时间：2018-04-27 23:30

本文选题：高血压 + 心血管重构　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:探讨心肌尔康多糖提取物对L-NAME诱导高血压小鼠心血管重构的影响,并对其可能的作用机制进行了初步分析。方法:昆明种小鼠50只,♂,清洁级,按体重随机分为对照组、模型组、多糖组、心肌尔康组和福辛普利组。除对照组外其余各组均以L-NAME诱导建立慢性高血压模型,后三组在造模4weeks后再分别用心肌尔康多糖、心肌尔康全方以及阳性药福辛普利继续灌胃给药4weeks,对照组小鼠8weeks内均自由食水,每周末tail-cuff测定尾动脉收缩压(systolic blood pressure,SBP),连续8weeks。第8周末,右颈动脉心脏插管测定各组小鼠左室舒张末期压(left ventricular end-diastolic pressure,LVEDP)、左室收缩末期压(left ventricular systolic pressure,LVSP)以及左心室压力变化最大速率(maximal rate of left ventricular pressure,±dp/dtmax)。充分暴露胸腔取心脏、和主动脉胸段行相关指标检测。精密称量小鼠体质和心脏质量并计算心重指数(心脏质量/体质量,HW/BW)。心脏切片经苏木素-伊红(hematoxylin and eosin,HE)、胶原纤维(Van Gieson,VG)染色,胸主动脉经苏木素-伊红(hematoxylin and eosin,HE)染色并分别观察其病理学变化。内皮依赖性血管舒张功能由体外血管环实验测定。分别采用硫代巴比妥酸法(thiobarbituric acid,TBA)、黄嘌呤氧化酶法、硝酸还原酶法检测血清中丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活性、一氧化氮(nitric oxide,NO)的含量。酶联免疫吸附测定(ELISA)法检测血清中非对称二甲基精氨酸(asymmetric dimethylarginine,ADMA)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)的含量以及血清和心肌组织中白介素1β(interleukin 1β,IL-β)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)以及白介素10(interleukin 10、IL-10)的含量。采用免疫组化(immunocytochemistry)方法检测心肌组织中IL-β、TNF-α、IL-10蛋白表达水平。结果:给药4weeks后,与L-NAME模型组相比,心肌尔康多糖组,心肌尔康全方组,阳性药福辛普利组明显抑制SBP、HW/BW、LVSP和+dp/dtmax的升高(P0.01,P0.05)。病理学结果显示,给予心肌尔康多糖,心肌尔康全方,阳性药福辛普利处理4weeks后,心肌横截面面积(cross-sectional area,CSA)、胶原容积分数(collagen volume fraction,CVF)、血管周胶原面积(perivscular collagen area,PVCA)、中膜厚度(media thickness,MT)均明显减小(P0.01),提高血清中SOD活性、e NOS活性(P0.01,P0.05),抑制血清中MDA含量、ADMA水平的升高(P0.01,P0.05)。心肌组织和血清中IL-β、TNF-α含量显著降低(P0.01,P0.05)而IL-10含量明显升高(P0.01,P0.05)。结论:心肌尔康多糖提取物通过改善内皮功能紊乱、降低机体氧化应激水平以及恢复免疫平衡,发挥对L-NAME诱导高血压小鼠心血管重构保护作用。
[Abstract]:Aim: to investigate the effect of Xinjinerkang polysaccharide extract on cardiovascular remodeling induced by L-NAME in hypertensive mice and its possible mechanism. Methods: fifty Kunming mice of clean grade were randomly divided into control group, model group, polysaccharide group, myocardial Erkang group and fosinopril group according to their body weight. The model of chronic hypertension was induced by L-NAME in all the other groups except the control group. The latter three groups were treated with Myocardial Erkang polysaccharide after 4weeks. Xin-er Kang Quan Fang and positive drug fosinopril continued to be administered intragastric for 4 weeks. Control mice were given free drinking water in 8weeks. Systolic blood pressure of the tail artery was measured by tail-cuff for 8 weeks at the end of the week. At the end of the 8th week, left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVSP) and maximal rate of left ventricular pressure change (maximal rate of left ventricular pressure, 卤DP 路dtmax) were measured by right carotid artery catheterization. The heart and thoracic segment of aorta were detected. The body mass and heart mass of mice were accurately weighed and the heart weight index (heart mass / body mass) was calculated. The heart sections were stained with hematoxylin and eosin HEG, and the thoracic aorta were stained with hematoxylin and eosin HEG and the pathological changes were observed. Endothelium-dependent vasodilation function was measured by in vitro vascular ring experiment. The contents of malondialdehyde (malondialdehyde), superoxide dismutase (SOD) and nitric oxide (no) in serum were determined by thiobarbituric acid method, xanthine oxidase method and nitrate reductase method respectively. Enzyme-linked immunosorbent assay (Elisa) for the detection of asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (Enos), interleukin 1 尾 (IL 1 尾), tumor necrosis factor 伪 (TNF- 伪) and endothelium nitric oxide synthase (Enos) in serum and myocardium The content of interleukin 10(interleukin 10 (IL 10). The expression of IL-10 protein in myocardial tissue was detected by immunocytochemistrymethod. Results: compared with the model group of L-NAME, the positive drug fosinopril inhibited the increase of SBPH-HW / BW-LVSP and dp/dtmax, compared with the model group of L-NAME, and the positive drug fosinopril inhibited the increase of SBPH-HW / BW-LVSP and dp/dtmax (P0.01) P0.05A, compared with the model group of L-NAME, the positive drug fosinopril group. The pathological results showed that after 4weeks was treated with Myocardial polysaccharides, Myocardial Kangquan recipe, positive drug fosinopril, Myocardial cross-sectional area, collagen volume fraction, perivascular collagen area, perivascular collagen area and media thickness significantly decreased P0.01G, increased the activity of SOD, P0.01P0.05, and inhibited the increase of MDA content in serum P0.01P0.05a. The content of IL- 尾 -TNF- 伪 in myocardium and serum decreased significantly (P 0.01), while the content of IL-10 increased significantly (P 0.01) and P 0.05 (P 0.05). Conclusion: the polysaccharides extract of Xinjinerkang can improve endothelial dysfunction, decrease the level of oxidative stress and restore the immune balance, so as to exert the protective effect on cardiovascular remodeling induced by L-NAME in hypertensive mice.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R965

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