Zhao Jian, Cao Mei, Zhang Jie, Sun Qun, Chen Qian, Yang Zhi-Rong
Division of Cancer Biotherapy, State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu 610064, PR China.
Peptides. 2006 Dec;27(12):3047-52. doi: 10.1016/j.peptides.2006.08.015. Epub 2006 Oct 12.
The pathological effects of alpha-amanitin on BALB/c mice after receiving intravenous injection were evaluated by RP-HPLC and mouse genome oligonucleotide microarray. The content of alpha-amanitin in Amanita virosa was about 2833.8 microg/g dry fruiting body. The liver and kidneys showed critical pathological changes after alpha-amanitin poisoning, and sera BUN, Crea, ALT, AST, TBIL and DBIL were the sensitive markers. The compound alpha-amanitin was detected in liver and kidney tissue homogenates by RP-HPLC after 48 h. The results of mouse genome oligonucleotide microarray showed 146 genes' expression changed, which formed the alternant network. The expression of 66 genes decreased, while 80 ones increased with more than two-fold differential expression after 48 h. The compound alpha-amanitin influenced not only RNA polymerase II, but also the expression of its associated genes. The application of mouse oligo chip provided valuable data for further understanding the biological properties and molecular pathogenesis of alpha-amanitin, also might be helpful for screening the curative drug for alpha-amanitin intoxication.
通过反相高效液相色谱法（RP-HPLC）和小鼠基因组寡核苷酸微阵列评估静脉注射α-鹅膏毒肽后对BALB/c小鼠的病理影响。毒蝇伞中α-鹅膏毒肽的含量约为2833.8微克/克干子实体。α-鹅膏毒肽中毒后肝脏和肾脏出现严重病理变化，血清尿素氮、肌酐、谷丙转氨酶、谷草转氨酶、总胆红素和直接胆红素是敏感指标。48小时后通过RP-HPLC在肝脏和肾脏组织匀浆中检测到化合物α-鹅膏毒肽。小鼠基因组寡核苷酸微阵列结果显示146个基因的表达发生变化，形成了交替网络。48小时后，66个基因的表达下降，80个基因的表达增加，差异表达超过两倍。化合物α-鹅膏毒肽不仅影响RNA聚合酶II，还影响其相关基因的表达。小鼠寡核苷酸芯片的应用为进一步了解α-鹅膏毒肽的生物学特性和分子发病机制提供了有价值的数据，也可能有助于筛选α-鹅膏毒肽中毒的治疗药物。
