天麻素对小鼠肝脏缺血再灌注损伤的保护作用

The protective effect of gastrodin on the hepatic ischemia-reperfusion injury in mice

目的探讨天麻素（Gas）对小鼠肝脏缺血再灌注损伤（HIRI）的作用及机制。方法40只C57BL／6雄性小鼠随机分为：假手术（Sham）组、HIRI组、天麻素低剂量（Gas—L）组、天麻素高剂量（Gas—H）组、钴原卟啉（CoPP）组，每组各8只。术前Gas—L组、Gas—H组、CoPP组腹腔注射相应剂量药物。除Sham组外，其他组70％肝脏缺血60min再灌注6h。比较各组血清AST、ALT水平；检测肝组织超氧化物歧化酶（SOD）、丙二醛（MDA）；实时荧光定量聚合酶链反应检测肝组织肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和10（IL-10）、血红素氧合酶-1（HO-1）的表达；肝组织苏木精-伊红染色；TUNEL法检测肝细胞凋亡。结果HIRI组、Gas—L组、Gas—H组和CoPP组ALT水平分别为（5057．34±290．80）U／L、（3917．49±198．10）U／L、（3645．63±171．10）U／L和（2977．78±179．00）U／L，AST分另0为（5871．25±819．01）U／L、（4660．88±505．96）U／L、（4182．25±507．51）U／L、（3788．65±462．14）U／L。Gas—L组、Gas—H组和CoPP组血清ALT、AST低于HIRI组，差异有统计学意义（P〈0．05）。Gas—L组、Gas—L组和CoPP组肝细胞凋亡指数分别为（37．89±4．27）％、（32．59±3．78）％、（20．45±2．49）％，低于HIRI组（58．92±3．32）％，差异有统计学意义（P〈0．05）。与HIRI组比较，Gas—L组、Gas-H组和CoPP组TNF—α和IL-6mRNA相对表达明显降低，IL-10和HO-1mRNA表达升高，SOD活性升高，MDA水平降低，差异有统计学意义（P〈0．05）。结论天麻素通过抗炎、抗氧化和抗细胞凋亡的作用减轻小鼠HIRI，其机制可能与促进HO-1的表达有关。

Objective To investigate the protective effect of gastrodin （Gas） on the hepatic ischemia-reperfusion injury （HIRI） in mice, and study possible mechanisms. Methods Forty male C57BL/6 mice were randomly divided into sham-operated group （ Sham）, HIRI group, gastrodin-treated groups with low and high does （ Gas-L, Gas-H, respectively）, and cobalt protoporphyrin （ CoPP ） group （ n = 8 ）. Mice in Gas-L, Gas-H, and CoPP groups were injected intraperitoneally with individual drugs and dose before opera- tion. Except for Sham group, an 70% volume HIRI model was established by means of 60 minutes ischemia and then 6 hours reperfusion in the other groups. The levels of serum AST and ALT in each group were compared. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in the liver tissue were measured; The level of TNF-α, IL-6, IL-10 and heine oxygenase-1 （HO-1） mRNA level were detected by real time quantitative PCR. Liver tissue was stained with H＆E . The hepatocyte apoptosis was studied by TUNEL. Results Respectively, the serum ALT level in the HIRI, Gas-L, Gas-H and CoPP groups was （5 057.34±290.80） U/L, （3 917.49-＋ 198.10） U/L, （3 645.63± 171.10） U/L, （2 977.78± 179.00） U/L, and the ALT level was （ 5 871.25 ± 819. 01 ） U/L, （ 4 660.88 ± 505.96） U/L, （ 4 182.00±507.51 ） U/L, （3 788.65±462.14）U/L. The serum level of ALT and AST in Gas-L, Gas-H and CoPP groups was lower than HIRI group （P〈 0.05 ）. The apoptotic index in Gas-L, Gas-H and CoPP groups respectively was （37.89±4.27） %, （32.59±3.78） %, （20.45±2.49） %, which was lower than group （58.92±3.32） % （ P〈 0.05）. Compared with HIRI group, the TNF-α and IL-6 mRNA level in Gas-L, Gas-H and CoPP groups were decreased, and the levels of IL-10 and HO-1 mRNA were increased. Simultaneously, the activity of SOD was promoted, whereas the levels of MDA was reduced （P〈0.05）. Conclusions Gastrodin shows an protective function aganist liver ischemia-reperfusion injury in mice by inhibiting inflammation, oxidative stress and cell apoptosis. The up-regulation of HO-1 by gastrodin may be the possible mechanism.