Settivari R S, Bhusari S, Evans T, Eichen P A, Hearne L B, Antoniou E, Spiers D E
Division of Animal Sciences, University of Missouri, Columbia, 65211, USA.
J Anim Sci. 2006 May;84(5):1279-94. doi: 10.2527/2006.8451279x.
Fescue toxicosis is caused by consumption of toxins produced by an endophytic fungus, Neotyphodium coenophialum, in tall fescue [Lolium arundinaceum (Schreb.) Darbysh]. Microarray analysis was used to identify shifts in genetic expression associated with the affected physiological processes to identify potential targets for future pharmacological/toxicological intervention. Male rats (n = 24) were implanted with temperature transmitters, which measure core temperature every 5 min. After an 8-d recovery, the rats were fed an endophyte-free diet for 5 d. During the following 5-d treatment period, rats were fed either an endophyte-free or an endophyte-infected (91.5 microg of ergovaline.kg of BW(-1).d(-1)) diet. At the end of treatment, rats were euthanized and a sample of the liver was obtained. Feed conversion efficiency was calculated for both treatment groups. Serum prolactin concentrations were measured using ELISA. Liver tissue RNA was reverse transcribed and hybridized to an oligonucleotide microarray chip. Microarray data were analyzed using a 2-step ANOVA model and validated by quantitative real-time PCR. Significant reductions in mean core temperature, feed intake, feed conversion efficiency, BW, liver weight per unit of BW, and serum prolactin concentrations were observed in endophyte-infected rats. There was downregulation (P < 0.05) of various genes associated with energy metabolism, growth and development, and antioxidant protection, as well as an upregulation of genes associated with gluconeogenesis, detoxification, and biotransformation. This study demonstrated that even short-term exposure of rats to tall fescue endophytic toxins under thermoneutral conditions can result in physiological responses associated with altered gene expression within the liver.
牛尾草中毒是由内生真菌Neotyphodium coenophialum在高羊茅[Lolium arundinaceum (Schreb.) Darbysh]中产生的毒素引起的。利用微阵列分析来确定与受影响的生理过程相关的基因表达变化，以识别未来药理学/毒理学干预的潜在靶点。雄性大鼠（n = 24）植入温度传感器，每5分钟测量一次核心体温。经过8天的恢复后，大鼠食用不含内生真菌的饲料5天。在接下来的5天治疗期内，大鼠分别食用不含内生真菌或感染内生真菌（91.5微克麦角缬氨酸·千克体重-1·天-1）的饲料。治疗结束时，对大鼠实施安乐死并获取肝脏样本。计算两个治疗组的饲料转化效率。使用酶联免疫吸附测定法测量血清催乳素浓度。将肝组织RNA进行逆转录并与寡核苷酸微阵列芯片杂交。使用两步方差分析模型分析微阵列数据，并通过定量实时聚合酶链反应进行验证。在感染内生真菌的大鼠中，观察到平均核心体温、采食量、饲料转化效率、体重、单位体重肝脏重量和血清催乳素浓度显著降低。与能量代谢、生长发育和抗氧化保护相关的各种基因下调（P < 0.05），同时与糖异生、解毒和生物转化相关的基因上调。本研究表明，即使在热中性条件下大鼠短期接触高羊茅内生真菌毒素，也会导致与肝脏内基因表达改变相关的生理反应。
