本文選題：心肌爾康　切入點：L-NAME　出處：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：目的:探討心肌爾康對L-NAME誘導(dǎo)高血壓小鼠心血管重構(gòu)的影響。探究其可能的機制;比較心肌爾康各劑量組的藥理學差異。方法:實驗采用60只雄性昆明小鼠,隨機分為正常組、模型組、心肌爾康低劑量組、中劑量組、高劑量組和厄貝沙坦組。除正常組外其余5組均以L-NAME誘導(dǎo)建立慢性高血壓模型。其中正常組自由飲食飲水,后5組加入L-NAME(2mg/ml),持續(xù)給藥8wk,自第5wk起每天灌胃給予心肌爾康3.75g/kg,7.5g/kg,15g/kg,厄貝沙坦40mg/kg,每天1次,連續(xù)4wk。期間每周測小鼠尾動脈壓,實驗第8wk末,右頸動脈插管測定血流動力學參數(shù)。收集血樣品后,充分暴露胸腔,獲取心臟和胸主動脈進行相關(guān)指標檢測。準確稱量小鼠體重和心臟質(zhì)量,計算心臟指數(shù)(心臟質(zhì)量/體質(zhì)量,HW/BW)。心肌標本進行蘇木素-伊紅(hematoxylin and eosin,HE)和膠原纖維(Van Gieson,VG)染色,胸主動脈經(jīng)HE染色,觀察其病理學變化。另取一段胸主動脈進行體外內(nèi)皮依賴性血管舒張功能實驗。分別采用硝酸還原酶法、黃嘌呤氧化酶法、硫代巴比妥酸法(thiobarbituric acid,TBA)、測定血清中一氧化氮(nitric oxide,NO)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)含量。雙抗體一步夾心法酶聯(lián)免疫吸附試驗(ELISA)檢測血清中非對稱二甲基精氨酸(asymmetrical dimethylarginine,ADMA)和內(nèi)皮型NO合酶(endothelial nitric oxide synthase,e NOS)的含量。采用蛋白印跡(western blot,WB)和免疫組化(immunocytochemistry)方法檢測心肌組織中e NOS的蛋白表達水平。結(jié)果:給藥4wk后,與正常組相比,模型組收縮壓(systolic blood pressure,SBP)明顯升高(P0.01),經(jīng)心肌爾康各個劑量組以及厄貝沙坦組實驗治療后,心肌爾康中劑量組能夠明顯抑制SBP、HW/BW、LVSP和+dp/dtmax升高(P0.01,P0.05)。病理學結(jié)果顯示,經(jīng)藥物實驗治療后,心肌橫截面面積(cross-sectional area,CSA)、膠原容積分數(shù)(collagen volume fraction,CVF)、血管周膠原面積(perivscular collagen area,PVCA)、中膜厚度(media thickness,MT)均明顯減小(P0.01)。表明心肌爾康能夠抑制心肌纖維化,改善胸主動脈發(fā)生的明顯重構(gòu)。與正常組相比,模型組血清NO和SOD含量明顯降低(P0.01),模型組小鼠血清中MDA含量明顯升高(P0.01)。與模型組相比,心肌爾康能提升NO含量和SOD活性(P0.01),降低MDA含量(P0.01)和ADMA(P0.05)含量。心肌組織中心肌爾康中劑量組能夠明顯抑制e NOS蛋白表達降低(P0.05)。結(jié)論:心肌爾康能對L-NAME誘導(dǎo)的高血壓小鼠發(fā)揮保護作用,其可能的藥理學機制至少部分與改善內(nèi)皮細胞功能紊亂,降低ADMA的含量以及降低氧化應(yīng)激水平相關(guān)。
[Abstract]:Objective: to investigate the effect of Xinjierkang on cardiovascular remodeling induced by L-NAME in hypertensive mice, to explore its possible mechanism, and to compare the pharmacological differences of different dose groups of Xinjinerkang. Methods: 60 male Kunming mice were randomly divided into normal group. Model group, low dose group, middle dose group, high dose group and irbesartan group. The model of chronic hypertension was induced by L-NAME in 5 groups except normal group. The latter five groups were treated with L-NAME-2mg / ml of L-NAME-2mg / ml for 8 wks. since 5wk, the rats were given intragastric administration of Myocardial Ercon 3.75g / kg 7.5g / kg 15g / kg, irbesartan 40mg / kg, once a day for 4 wks. during which the caudal arterial pressure of mice was measured every week, and the end of the experiment was the end of 8wk. The hemodynamic parameters were measured by right carotid artery intubation. After collecting blood samples, the thoracic cavity was fully exposed, and the heart and thoracic aorta were obtained to detect the relevant indexes. The weight and heart quality of the mice were weighed accurately. Myocardial samples were stained with hematoxylin and eosin hehe and collagen fiber Van Giesonne VG. The thoracic aorta was stained with HE. Another segment of thoracic aorta was taken for endothelium-dependent vasodilation in vitro. Nitrate reductase method and xanthine oxidase method were used respectively. Thiobarbituric acid (TBAA) was used to determine serum nitric oxide (no), superoxide dismutase (SOD), malondialdehyde (MDA), malondialdehyde (malondialdehyde) (malondialdehyde) (malondialdehyde (MDA)) in serum. Two antibody sandwich enzyme-linked immunosorbent assay (ELISAs) was used to detect asymmetric dimethylarginine (ADMA) and asymmetric dimethylarginine (ADMA) in serum. The expression of e NOS protein in myocardial tissue was detected by Western blotDNA and immunocytochemistryassay methods. Results: after the administration of 4wk, the expression of e NOS in myocardium was detected by Western blotblotBand immunohistochemistry. Results: the expression of e NOS in myocardium was detected by Western blotblotBand immunohistochemical method. Results: after the administration of 4wk, the expression of e NOS in myocardial tissue was detected. Compared with the normal group, systolic blood pressure of SBP in the model group was significantly higher than that in the control group. After experimental treatment with various doses of Myocardial Erkang and irbesartan group, the moderate dose group could significantly inhibit the increase of SBP HW / BWN LVSP and dp/dtmax. The pathological results showed that, After drug treatment, myocardial cross-sectional area, collagen volume fractionation, perivascular collagen area and media thicknessn were significantly decreased (P 0.01). Compared with the normal group, the serum no and SOD levels in the model group were significantly lower than those in the model group, while the MDA content in the serum of the model group was significantly higher than that in the model group, and that in the model group was significantly higher than that in the model group. Xinjierkang can increase the content of no and SOD activity (P0.01), decrease the contents of MDA (P0.01) and ADMA-P0.05). The middle dose group of myocardial tissue can obviously inhibit the expression of e NOS protein and decrease the expression of P0.050.Conclusion: Xenerkang can treat hypertension induced by L-NAME. Mice play a protective role, The pharmacological mechanism may be related at least in part to the improvement of endothelial cell dysfunction, the reduction of ADMA content and the reduction of oxidative stress.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R965

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