木樨草素等抗心肌缺血/再灌注损伤及抑制脂代谢和细胞凋亡作用研究
Effects of Luteolin and Its Analogues Against Myocardial Ischemia/Reperfusion Injury， Lipid Metabolism and Apoptosis
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摘要: 目的 探讨香青兰中木樨草素、山奈酚和木樨草苷对大鼠离体心肌缺血/再灌注损伤(MIRI)模型的保护作用及其抑制脂代谢相关酶11β-羟基类固醇脱氢酶1型（11β-HSD1）、溶血磷脂酸酰基转移酶(LPAATs)和细胞凋亡相关蛋白磷酸酯酶和张力蛋白同系物（PTEN）、蛋白酪氨酸磷酸酶2（SHIP-2）的作用，探讨中药多成分、多靶点抗MIRI的机制。方法 采用Langendorff装置，以洛-林二氏溶液为灌流液，通过停灌和复灌心脏建立MIRI模型，检测心率(HR)、左室舒张末压(LVEDP)、左室发展压(LVDP)、(-dp/dt)/(+dp/dt)、冠脉流量(CF)、乳酸脱氢酶(LDH)、心肌梗死面积。ELISA法测定LPAATβ和11β-HSD1活性。分光光度法测定PTEN和SHIP-2活性。结果 木樨草素、山奈酚和木樨草苷保护HR，降低LDH过量释放，升高LVEDP、LVDP和(-dp/dt)/(+dp/dt)，恢复CF，降低心肌梗死面积。LPAATβ、11β-HSD1、PTEN、SHP-2等蛋白活性受木樨草素等的抑制。结论 木樨草素、山奈酚和木樨草苷具有通过抗脂代谢紊乱和抗细胞凋亡分子机制保护大鼠离体心脏MIRI的作用。Abstract: OBJECTIVE To explore the multi-component and on MIRI model rat multi-target mechanism of Chinese medicine against MIRI， the protective effects of luteolin， kaempferol and luteoloside on rat MIRI， and the inhibition on lipid-metabolization-related enzymes 11β-HSD1， LPAATβ， and apoptosis-related enzymes PTEN， and SHP-2. METHEODS Using a Langendorff apparatus， the MIRI model was established by stopping perfusion and reperfusion with oxygenated Locke-Ringer's solution. The HR， LVEDP， LVDP， (-dp/dt)/(+dp/dt)， CF， LDH and myocardial infarct size were assayed. LPAATβ and 11β-HSD1 were assayed by spectrophotometry. The inhibition of PTEN and SHP-2 activity was measured by spectrophotometry. RESULTS Luteolin， kaempferol and luteoloside could protect HR， reduce LDH release， raise LVDP， LVEDP and (-dp/dt)/ (+dp/dt)， recover CF， and reduce myocardial infarct size， respectively. Moreover， the activities of LPAATβ， 11β-HSD1， PTEN and SHP-2 were repressed by pretreatment with luteolin， kaempferol and luteoloside. CONCLUSION Luteolin， kaempferol and luteoloside show the cardioprotective effects on MIRI of isolated rat heart by against lipid metabolism disorders and apoptosis.
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