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内生真菌感染高羊茅种子提取物引起牛血管收缩的作用类似于纯麦角酰二乙胺。

Constriction of bovine vasculature caused by endophyte-infected tall fescue seed extract is similar to pure ergovaline.

机构信息

Department of Animal and Food Sciences, University of Kentucky, Lexington 40546-0215, USA.

出版信息

J Anim Sci. 2012 May;90(5):1603-9. doi: 10.2527/jas.2011-4513. Epub 2011 Dec 6.

Abstract

Ergovaline has been extensively used to study vasoactive effects of endophyte- (Neotyphodium coenophialum) infected tall fescue (Lolium arundinaceum). However, initial results indicated that an extract of toxic tall fescue seed (E+EXT) is more potent than ergovaline alone in a right ruminal artery and vein bioassay. The E+EXT induced a greater contractile response than an equal concentration of ergovaline alone in the ruminal artery of heifers (P = 0.018). This led to a hypothesis that other compounds in the seed extract contribute to vasoconstriction. Thus, experiments were conducted to determine if vasoactivity of an E+EXT is different from a mixture of ergot alkaloids (ALK; ergovaline, ergotamine, ergocristine, ergocryptine, ergocornine, ergonovine, and lysergic acid) of similar concentrations and to determine if the vasoactivity of an E+EXT differs from an endophyte-free tall fescue seed extract (E-EXT). Segments of lateral saphenous vein and right ruminal artery and vein were collected from Holstein steers (n = 6) shortly after slaughter. Vessels were cleaned of excess connective tissue and fat and sliced into segments that were suspended in a multimyograph chamber with 5 mL of continually oxygenated Krebs-Henseleit buffer, equilibrated for 90 min, and exposed to a reference compound (120 mM KCl for ruminal vessels and 0.1 mM norepinephrine for saphenous vein). Increasing concentrations of each treatment (E+EXT, E-EXT, ALK, and ergovaline) were added to the respective chamber every 15 min after buffer replacement. Data were normalized as a percentage of maximal contractile response of the reference compound and fit to a sigmoidal concentration response curve. Ergovaline, ALK, and E+EXT induced similar responses in the saphenous vein, ruminal artery, and ruminal vein. The E+EXT displayed a smaller EC(50) (half maximal effective concentration) than ergovaline or ALK in the saphenous vein and ruminal vein (P < 0.008), but not the ruminal artery (P = 0.31). Extrapolated maximum response was greatest in the saphenous vein for ergovaline, least for E+EXT, and intermediate for ALK (P < 0.0001). The E-EXT did not induce a contractile response in any vessel tested (P > 0.1). Data from this study indicate that ergovaline is largely responsible for the locally induced vasoconstriction of bovine vasculature observed with endophyte-infected tall fescue.

摘要

麦角孤生物碱已被广泛用于研究内生真菌(Neotyphodium coenophialum)感染的高羊茅(Lolium arundinaceum)的血管活性作用。然而,最初的结果表明,在右瘤胃液动静脉生物测定中,有毒高羊茅种子的提取物(E+EXT)比单独的麦角孤生物碱更有效。E+EXT 在小母牛的瘤胃液动脉中引起的收缩反应大于单独等浓度的麦角孤生物碱(P=0.018)。这导致了一个假设,即种子提取物中的其他化合物有助于血管收缩。因此,进行了实验以确定 E+EXT 的血管活性是否与类似浓度的麦角生物碱(ALK;麦角孤碱、麦角胺、麦角新碱、麦角隐亭、麦角柯宁、麦角新碱和麦角酸)混合物不同,并确定 E+EXT 的血管活性是否与无内生真菌的高羊茅种子提取物(E-EXT)不同。在屠宰后不久,从荷斯坦公牛(n=6)中收集了外侧隐静脉和右瘤胃液动静脉段。将血管从多余的结缔组织和脂肪中清洗干净,切成段,悬挂在多肌描记器室中的 5 mL 持续充氧的 Krebs-Henseleit 缓冲液中,平衡 90 min,并暴露于参考化合物(瘤胃液血管为 120 mM KCl,隐静脉为 0.1 mM 去甲肾上腺素)。在缓冲液更换后每 15 min 向各自的室中添加每种处理(E+EXT、E-EXT、ALK 和麦角孤碱)的递增浓度。数据作为参考化合物最大收缩反应的百分比进行归一化,并拟合到 sigmoidal 浓度反应曲线。麦角孤碱、ALK 和 E+EXT 在隐静脉、瘤胃液动脉和瘤胃液静脉中引起相似的反应。E+EXT 在隐静脉和瘤胃液静脉中的 EC50(半最大有效浓度)小于麦角孤碱或 ALK(P<0.008),但在瘤胃液动脉中则不然(P=0.31)。最大反应的外推值在隐静脉中对麦角孤碱最大,对 E+EXT 最小,对 ALK 居中(P<0.0001)。E-EXT 在任何测试的血管中均未引起收缩反应(P>0.1)。本研究的数据表明,麦角孤生物碱在很大程度上负责观察到的内生真菌感染高羊茅引起的牛血管局部血管收缩。

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