目的 探讨栀子苷对肝脏缺血再灌注损伤大鼠炎症反应、氧化应激和PI3K/Akt信号通路的影响。方法 将SD大鼠分为对照组、模型组和栀子苷5、10 mg/kg组,每组各10只。对照组、模型组大鼠ip溶剂橄榄油10 mg/kg,栀子苷5、10 mg/kg组大鼠ip栀子苷5、10 mg/kg,连续7 d,最后一次注射药物后进行肝缺血再灌注损伤建模处理。检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素、直接胆红素以及肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、白细胞介素(IL)-6、IL-1β水平;测定肝组织丙二醛(MDA)、谷胱甘肽(GSH)、诱导型一氧化氮合酶(iNOS)、超氧化物歧化酶(SOD)水平;观察肝组织病理学变化和细胞凋亡;检测肝组织凋亡相关因子Bcl-2、Bax mRNA表达及p-PI3K、PI3K、p-Akt、Akt、Bcl-2、Bax、cleaved Caspase-3、Caspase-3蛋白表达。结果 与模型组相比,栀子苷5、10 mg/kg组血清ALT、AST、总胆红素、直接胆红素水平、TNF-α、TGF-β、IL-6、IL-1β、MDA和iNOS水平、肝组织凋亡细胞比例、Bax mRNA、蛋白表达和cleaved Caspase-3/Caspase-3显著降低(P<0.05),GSH、SOD水平、Bcl-2 mRNA和蛋白表达、p-PI3K/PI3K和p-Akt/Akt显著升高(P<0.05),且栀子苷10 mg/kg组作用效果更明显(P<0.05)。结论 栀子苷能够改善大鼠肝功能,减轻氧化应激、炎症反应和细胞凋亡,其作用机制可能是通过激活PI3K/Akt信号通路实现的。

Objective To investigate the effects of geniposide on inflammatory response, oxidative stress, and PI3K/Akt signaling pathway in rats with hepatic ischemia-reperfusion injury. Methods All SD rats were divided into control group, model group, and geniposide (5 and 10 mg/kg) groups, and each group had 10 rats. The rats in the control group and model group were given ip solvent olive oil 10 mg/kg, and the rats in the geniposide (5 and 10 mg/kg) groups were ip administered with geniposide 5 and 10 mg/kg. All rats were treated for 7 d after the last drug injection, and were treated to model liver ischemia-reperfusion injury. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin and tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-1β were detected. The levels of malondialdehyde (MDA), glutathione (GSH), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) were detected. The pathological changes and apoptosis of rat liver tissue were observed. The expression of Bcl-2, Bax mRNA, and p-PI3K, PI3K, p-Akt, p-PI3K, PI3K, p-Akt, Akt, Bcl-2, Bax, cleaved Caspase-3, and Caspase-3 protein were detected. Results Compared with model group, the serum levels of ALT, AST, total bilirubin, direct bilirubin, TNF-α, TGF-β, IL- 6, IL-1β, MDA, and iNOS, the proportion of apoptotic cells in liver tissue, the expression of Bax mRNA, protein, and cleaved Caspase-3/Caspase-3 in geniposide (5, 10 mg/kg) groups were significantly decreased (P＜0.05). The levels of GSH and SOD, the expression of Bcl-2 mRNA and protein, and p-PI3K/PI3K and p-Akt/Akt were significantly increased (P＜0.05). And the effect of 10 mg/kg geniposide had a more significant effect (P＜0.05). Conclusion Geniposide can improve rat liver function, reduce oxidative stress, inflammatory response, and apoptosis, and its mechanism may be achieved by activating PI3K/Akt signaling pathway.

R285.5

河南省医学科技攻关计划联合共建立项项目(LHG202000475)