高膽固醇血症感壓反射減弱之研究：一氧化氮及厚朴的影響; Effect of Magnolia Officinalis and Nitric Oxide on Baroreflex Function in Hypercholesteremia

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题名:	高膽固醇血症感壓反射減弱之研究：一氧化氮及厚朴的影響;Effect of Magnolia Officinalis and Nitric Oxide on Baroreflex Function in Hypercholesteremia
作者:	周佩玉;Chou, pey-ue
贡献者:	中國醫藥大學醫學研究所
关键词:	高膽固醇血症;感壓反射;一氧化氮;厚朴;Hypercholesteremia;Baroreflex;Nitric Oxide;Magnolia Officinalis
日期:	1993
上传时间:	2009-12-24 10:58:39 (UTC+8)
摘要:	血液中不正常的膽固醇累積，是造成粥狀動脈硬化的危險因子。高膽固醇血症的動物體內一氧化氮（NO）量是增加的，而且高膽固醇血症的動物感壓反射敏感度（baroreflex sensitivity，BRS）是變差的。有證據顯示NO會影響BRS，因此，高膽固醇血症的BRS變差，也許與NO有關。中藥厚朴被證實能夠改善高膽固醇血症，但是否能夠改善感壓反射並不清楚的。另外，在失血的特殊生理狀態下，身體的感壓反射功能也會改變，高膽固醇血症的動物在失血時感壓反射功能的表現，與正常的動物的反應是否有差異，其機轉是否也與NO有關，是否也受中藥厚朴的影響等問題，目前仍然是不清楚的。因此在我們的實驗中，主要的目的是在探討高膽固醇血症的病理狀況下，失血前後的感壓反射敏感度改變，是否與NO有關，同時也探討中藥厚朴對這些改變是否有影響。實驗將紐西蘭雄性大白兔分別分為三組：1.控制組(control group，餵食正常兔飼料)、2.膽固醇組(cholesterol group，餵食0.5%高膽固醇飼料)、3. 厚朴組 (magnolia group，餵食0.5%高膽固醇飼料中加1%厚朴粹取液)，每天各100克。在飼養4或8週，分別，記錄基礎血壓及心跳，並且測量血中膽固醇含量，及BRS。BRS係以升壓劑phenylephrine改變血壓，並造成反射性心跳改變，然後以線性迴歸方式分析。另外在第8週，也進行失血處理。並分別在失血前或失血後，給予L-NAME (20mg/kg,iv.) 抑制體內NO的製造，然後觀察血壓、心跳、及BRS等之改變。失血程度是以血壓降至50-60mmHg，並且同時看到原來變快的心跳，轉變成心跳減慢等條件為依據。在4週時，血壓、心跳以及BRS三組間並無顯著性之差異。在8週時，膽固醇及厚朴組動物的總膽固醇比控制組高，在統計上有顯著性的差異。而三酸甘油脂、心跳方面，三組間並無顯著性之差異。在血壓方面，膽固醇組及厚朴組也比控制組高。在BRS方面，則是控制組的高於膽固醇組及厚朴組，而厚朴組的又比膽固醇組還高。給予L-NAME抑制NO後，三組皆發現血壓增加，但是反射性心跳下降方面，只有膽固醇組才有統計差異。在BRS方面，膽固醇組及厚朴組在加L-NAME之後BRS皆提高。開始失血時，心跳會增加，到重度失血時心跳反而下降，降到一定程度後心跳值趨於穩定值。在失血後，膽固醇組的BRS依然低於控制組的失血後BRS，而厚朴組在失血前雖低於控制組，失血後，與控制組並無差異。失血後加L-NAME，各組的BRS皆有改善至未失血前之水準。所以，本實驗發現高膽固醇血症的兔子，其BRS顯著變差，可能與NO有關。失血也使BRS降低，也與NO有關。厚朴組的BRS雖比控制組低，但是不管失血前、失血後皆比高膽固醇的高，因此對高膽固醇引起的BRS減弱，有改善的作用，但是可能與NO無關。; Hypercholesterolemia is an important pathogenic factor in atherogenesis. In hypercholesterolemia, nitric oxide (NO) production was enhanced. Over production of NO was found to attenuate baroreflex function. This is consistent with the findings that baroreflex sensitivity (BRS) was depressed in hypercholesterolemia. The Chinese herb, Magnolia officinalis, was shown to improve hypercholesterolemia. However, whether the Magnolia officinalis could also improve BRS is not known. In some pathophysiological states, such as in hemorrhage, BRS was also depressed and could be attributed to NO. Whether the BRS depression in hypercholesterolemia in hemorrhage is also related to NO or whether it could be ameliorated by Magnolia officinalis remains unknown. The present study, therefore, was undertaken to investigate the following hypotheses: 1. the BRS in hypercholesterolemia may be attenuated in severe hemorrhage, 2. the attenuation of BRS may be mediated by NO, 3. besides improvement of hypercholesterolemia, Magnolia officinalis could also improve BRS in normal state as well as in severe hemorrhagic state, and 4. the action of Magnolia officinalis on BRS in hypercholesterolemia may be mediated by NO. Male New Zealand white rabbits were divided into 3 groups: 1. Control group (normal diet), 2. Cholesterol group (0.5% w/w cholesterol diet), or 3. Magnolia group (same as Cholesterol group but plus 1% w/w magnolia officiralis crude methanol extract). The animals were continuously treated under the designated diet for 4 or 8 weeks. BRS in the control of heart rate was determined by linear regression method. Hemorrhage was induced by bleeding from the arterial catheter, until a paradoxical decrease of heart rate from peak tachycardia and a drop of mean arterial blood pressure below 70 mmHg were both observed. The results demonstrated that arterial blood pressure (BP), heart rate (HR), and BRS were not different among groups after 4 weeks of diet treatment. However, after 8 weeks of treatment, plasma total cholesterol was significantly elevated in the Cholesterol and Magnolia groups. The BP was also increased in the Cholesterol and Magnolia groups. The BRS of the Cholesterol and Magnolia groups was both significantly depressed. However, the BRS of the Magnolia group was significantly greater than that of the Cholesterol group. After L-NAME (Nω-nitro-Larginine methyl ester, 20mg/kg, iv.), the BRS of the Cholesterol group was significantly improved. In response to hemorrhage, BRS was depressed in all 3 groups. But BRS was improved by L-NAME treatment in all 3 groups. In hemorrhage, the BRS of the Magnolia group was greater than that of the Cholesterol. The data suggested that BRS was depressed in hypercholesterolemia
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