褪黑素對(duì)實(shí)驗(yàn)性動(dòng)脈粥樣硬化兔心臟的保護(hù)作用及其可能的分子機(jī)制
本文選題:動(dòng)脈粥樣硬化 + 心肌組織; 參考:《安徽醫(yī)科大學(xué)學(xué)報(bào)》2017年12期
【摘要】:目的觀察褪黑素(MLT)對(duì)實(shí)驗(yàn)性動(dòng)脈粥樣硬化兔心臟的保護(hù)作用及其可能的分子機(jī)制。方法普通級(jí)純種新西蘭大耳白兔隨機(jī)分為3組,正常組:飼喂普通飼料;模型組:飼喂高脂飼料(普通飼料+1%膽固醇+5%豬油);褪黑素組:飼喂高脂飼料的同時(shí)MLT灌胃10 mg/(kg·d)治療。純種大耳白兔適應(yīng)性飼養(yǎng)一周后,采用高脂飲食誘導(dǎo)造模,同時(shí)給予褪黑素藥物治療。于12周后處死進(jìn)行采血,檢測(cè)血清中血脂等指標(biāo)。取動(dòng)脈進(jìn)行油紅染色,檢測(cè)脂質(zhì)斑塊形成情況;取心臟組織,包埋后HE染色觀察心肌組織的形態(tài)變化;Masson染色檢測(cè)心肌組織中膠原纖維的變化;Western blot法檢測(cè)p38/絲裂原活化蛋白激酶(MAPK)通路相關(guān)蛋白及肌球蛋白輕鏈激酶(MLCK)、肌球蛋白輕鏈(MLC)、肌球蛋白輕鏈磷酸化(p-MLC)的表達(dá)水平。結(jié)果動(dòng)脈油紅染色結(jié)果顯示模型組出現(xiàn)大量脂質(zhì)斑塊,證明造模成功。血脂結(jié)果顯示模型組總膽固醇(TCH)、三酰甘油(TG)濃度明顯上升,而褪黑素組相對(duì)模型組下降。油紅染色HE染色結(jié)果顯示MLT能改善心肌組織形態(tài)的紊亂情況,Masson染色結(jié)果顯示MLT能緩解心肌組織膠原纖維的堆積。Western blot結(jié)果顯示MLT能下調(diào)p38的磷酸化水平以及MLCK蛋白的表達(dá)水平,以及下調(diào)MLC的磷酸化表達(dá)水平(P0.05)。結(jié)論 MLT可能通過降低MAPK通路中相關(guān)蛋白p38的磷酸化調(diào)控MLCK蛋白的表達(dá),從而降低MLC的磷酸化水平對(duì)動(dòng)脈粥樣硬化兔心肌組織起到保護(hù)作用。
[Abstract]:Objective to investigate the protective effect of melatonin (MLT) on experimental atherosclerosis rabbit heart and its possible molecular mechanism. Methods New Zealand white rabbits were randomly divided into 3 groups. The model group was fed with high fat diet (1% cholesterol 5% lard) and melatonin group (fed with high fat diet and MLT for 10 mg/(kg). Purebred white rabbits were fed adaptively for one week, then induced by high fat diet and treated with melatonin. After 12 weeks, blood was collected and blood lipid was detected. The arteries were stained with oil red to detect the formation of lipid plaques. Morphological changes of Myocardial tissue observed by HE staining after embedding; changes of Collagen Fibers in Myocardial tissue by Masson staining; Detection of p38 / Mitogen-activated protein Kinase MAPK Pathway related proteins and Myosin Light chain Kinase (MLCKK), Myosin by Western blot The expression level of MLC, myosin light chain phosphorylated P-MLC. Results A large number of lipid plaques were found in the model group, which proved that the model was successful. The results showed that the concentrations of TCHG and TG in the model group were significantly increased, while those in the melatonin group were lower than those in the model group. The results of oil red HE staining showed that MLT could improve the disorder of myocardial morphology. The results showed that MLT could alleviate the accumulation of collagen fibers in myocardium. Western blot showed that MLT could down-regulate the phosphorylation of p38 and the expression of MLCK protein. The phosphorylation level of MLC was down-regulated (P 0.05). Conclusion MLT may play a protective role in myocardial tissue of atherosclerotic rabbits by decreasing the phosphorylation of p38 in MAPK pathway and regulating the expression of MLCK protein.
【作者單位】: 安徽醫(yī)科大學(xué)分子生物學(xué)實(shí)驗(yàn)室安徽省/省部共建教育部重要遺傳病基因資源利用重點(diǎn)實(shí)驗(yàn)室;
【基金】:國(guó)家自然科學(xué)基金(編號(hào):81570419) 安徽省高校省級(jí)自然科學(xué)研究項(xiàng)目(編號(hào):KJ2013Z127)
【分類號(hào)】:R54
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