为研究桦褐孔菌中总三萜类化合物（TIO）对对乙酰氨基酚（APAP）致小鼠肝损伤模型的保护作用及机制，该研究将SPF级ICR雄性小鼠48只，分为空白对照组、模型组、水飞蓟素组（50 mg/kg）、TIO低、中、高剂量组（15 mg/kg、30 mg/kg、60 mg/kg），连续给药7 d，末次给药后，除空白组小鼠外均一次性腹腔注射300 mg/kg APAP造肝损伤模型。测定小鼠体内丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、超氧化物歧化酶（SOD）的活性、还原型谷胱甘肽（GSH）和丙二醛（MDA）含量。同时取肝脏进行苏木精-伊红（HE）染色和Hoechst 33258染色，观察小鼠肝脏病理学改变。结果表明，与模型组比较，TIO高剂量干预组降低AST、ALT含量至8.38 U/L、11.13 U/L，降低MDA含量至20.71 pmol/(mg pro)，增加SOD、GSH水平至628.39 U/(mg pro)、126.28 U/(mg pro)。HE染色后，TIO中、高剂量干预与水飞蓟素组肝小叶结构基本完整清晰，肝细胞损伤程度有较大修复。Hoechst 33258染色后，TIO干预组凋亡肝细胞数量明显减少，且荧光团颜色减弱。以上结果说明桦褐孔菌中总三萜类化合物对APAP所致肝损伤小鼠有一定的保护作用。其机制可能与减轻氧化应激和抑制凋亡有关。

To study the action mechanisms of total triterpenoids (TIO) in Inonotus obliquus on acetaminophen (APAP)-induced liver injury in mice, a total of 48 SPF-grade ICR male mice were divided into six groups with seven-day administration as follows: blank control; model; silymarin-treated (50 mg/kg); and TIO-treated low , medium, and high dose (15 mg/kg, 30 mg/kg, and 60 mg/kg, respectively). After the last administration, all groups, except the blank group, were subjected to a one-time abdominal injection of 300 mg/kg APAP to establish the liver injury models. Subsequently, the activities of alanine aminotransferase, aspartate aminotransferase, and superoxide dismutase were determined, and the contents of reduced glutathione and malondialdehyde were measured. Furthermore, the liver was processed for hematoxylin–eosin and Hoechst 33258 staining to observe pathological changes. The high dose of TIO reduced the aspartate aminotransferase and alanine aminotransferase contents to 8.38 U/L and 11.13 U/L, respectively, and that of malondialdehyde to 20.71 pmol/(mg pro). The superoxide dismutase and reduced glutathione levels were increased to 628.39 U/(mg pro) and 126.28 U/(mg pro), respectively Hematoxylin-eosin staining revealed the structure of the liver lobules in the TIO-treated medium- and high-dose and the silymarin-treated groups to be complete and clear, and the liver cell injury to be effectively repaired. Hoechst 33258 staining showed that the numbers of apoptotic liver cells in the TIO-treated groups were significantly reduced, and the fluorophore color was weakened. The above results indicate that the total triterpenoids in Inonotus obliquus provide marked protection against APAP-induced liver injury in mice. The mechanism may be related to reduction in oxidative stress and inhibition of apoptosis.

吉林省科技发展重点成果转化项目(2016030710YY)