摘 要：目的 研究雷公藤固体发酵产物灵雷菌质的肝脏毒性。方法 SD大鼠随机分为对照组、灵雷菌质组、雷公藤组，灵雷菌质组及雷公藤组分别ig给予灵雷菌质、雷公藤95%乙醇提取物2.037 5、0.64 g/kg，每日给药1次，连续给药30 d。给药结束后检测大鼠血液生化指标，观察大鼠肝组织病理学改变，Western blotting检测大鼠肝组织中Nrf2、P38蛋白表达。结果 肝组织病理学观察可见，灵雷菌质组大鼠肝组织仅见中央细胞坏死，周边细胞局部胞质溶解，出现细胞凋亡；雷公藤组肝组织可见小片状坏死，核凋亡，肝细胞内胶原纤维明显，细胞溶解坏死。与对照组相比，灵雷菌质组、雷公藤组大鼠丙氨酸转氨酶（ALT）水平、核蛋白Nrf2和总蛋白P38表达升高，但灵雷菌质组的上述指标比雷公藤组显著下降（P＜0.05）。与对照组相比，灵雷菌质组、雷公藤组大鼠白蛋白（ALB）、总蛋白（TP）均下降（P＜0.05），而灵雷菌质组ALB、TP下降幅度较雷公藤组小（P＜0.05）。结论 灵雷菌质的肝脏毒性较雷公藤低，其毒性机制可能与激活P38 MARK和Nrf2-ARE信号通路、启动抗氧化作用有关。

Abstract: Objective To investigate the hepatotoxicity of Tripterygium wilfordii after ganoderma solid fermentation product—Ling-Lei fermentation substance. Methods SD rats were randomly separated into three groups: control (C), Ling-lei fermentation substance (LF), and T. wilfordii (TW) groups. SD rats in LF and TW groups were ig administered with 95% ethanol extract of Ling-lei fermentation substance and T. wilfordii at the doses of 2.037 5 and 0.64 g/kg, respectively once a day for consecutive 30 d. After administration, the blood biochemical index and liver histopathological examination were determined. The expression levels of Nrf2 and P38 protein in liver tissue were tested by Western blotting. Results The liver histopathological examination revealed that rats in LF group showed the central cells necrosis in liver tissue only, the local cytoplasm dissolved in peripheral cells, and the apoptosis appeared. Rats in TW group showed the small necrosis, nuclear apoptosis, obvious collagen fibers in liver cells, and cells dissolved the necrosis. Compared with C group, content of alanine aminotransferase (ALT), expression levels of nucleoprotein Nrf2 and P38 protein of rats in LF and TW groups increased, while these indicators in LF group decreased obviously compared with TW group (P < 0.05). The levels of albumin (ALB) and total protein (TP) in LF and TW groups decreased compared with C group (P < 0.05), while ALB and TP in LF group decreased significantly compared with TW group (P < 0.05). Conclusion The hepatotoxicity of Ling-lei fermentation substance is lower than that of T. Wilfordii, and its toxic mechanism may be associated with anti-oxidation initiated by activating the P38 MARK and the Nrf2-ARE signaling pathways.

基金项目：国家“973”资助项目（2009CB522801）