目的 探討梔子苷對(duì)肝臟缺血再灌注損傷大鼠炎癥反應(yīng)、氧化應(yīng)激和PI3K/Akt信號(hào)通路的影響。方法 將SD大鼠分為對(duì)照組、模型組和梔子苷5、10 mg/kg組,每組各10只。對(duì)照組、模型組大鼠ip溶劑橄欖油10 mg/kg,梔子苷5、10 mg/kg組大鼠ip梔子苷5、10 mg/kg,連續(xù)7 d,最后一次注射藥物后進(jìn)行肝缺血再灌注損傷建模處理。檢測(cè)血清丙氨酸氨基轉(zhuǎn)移酶(ALT)、天冬氨酸氨基轉(zhuǎn)移酶(AST)、總膽紅素、直接膽紅素以及腫瘤壞死因子-α(TNF-α)、轉(zhuǎn)化生長(zhǎng)因子-β(TGF-β)、白細(xì)胞介素(IL)-6、IL-1β水平;測(cè)定肝組織丙二醛(MDA)、谷胱甘肽(GSH)、誘導(dǎo)型一氧化氮合酶(iNOS)、超氧化物歧化酶(SOD)水平;觀察肝組織病理學(xué)變化和細(xì)胞凋亡;檢測(cè)肝組織凋亡相關(guān)因子Bcl-2、Bax mRNA表達(dá)及p-PI3K、PI3K、p-Akt、Akt、Bcl-2、Bax、cleaved Caspase-3、Caspase-3蛋白表達(dá)。結(jié)果 與模型組相比,梔子苷5、10 mg/kg組血清ALT、AST、總膽紅素、直接膽紅素水平、TNF-α、TGF-β、IL-6、IL-1β、MDA和iNOS水平、肝組織凋亡細(xì)胞比例、Bax mRNA、蛋白表達(dá)和cleaved Caspase-3/Caspase-3顯著降低(P<0.05),GSH、SOD水平、Bcl-2 mRNA和蛋白表達(dá)、p-PI3K/PI3K和p-Akt/Akt顯著升高(P<0.05),且梔子苷10 mg/kg組作用效果更明顯(P<0.05)。結(jié)論 梔子苷能夠改善大鼠肝功能,減輕氧化應(yīng)激、炎癥反應(yīng)和細(xì)胞凋亡,其作用機(jī)制可能是通過激活PI3K/Akt信號(hào)通路實(shí)現(xiàn)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

河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃聯(lián)合共建立項(xiàng)項(xiàng)目(LHG202000475)