β-谷甾醇通过PI3K/Akt信号通路减轻雄黄诱导的小鼠肝损伤  

β-sitosterol relieving realgar-induced liver injury in mice through PI3K/Akt signaling pathways

作　　者：苏海兴 侯崇智[1] 程涛 施伟栋[1] SU Hai-xing;HOU Chong-zhi;CHEN Tao;SHI Wei-dong(Department of General Surgery,Xi′an Children′s Hospital(Xi′an Shaanxi,710082),China.)

机构地区：[1]西安市儿童医院普外科,陕西西安710082

出　　处：《中西医结合肝病杂志》2024年第12期1083-1087,1095,共6页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：陕西省自然科学基础研究计划项目(No.S2021-JC-YB-2616)。

摘　　要：目的:探究β-谷甾醇对雄黄诱导的肝损伤小鼠的作用机制。方法:将36只小鼠分为对照组、模型组、阳性对照组(联苯双酯)、β-谷甾醇低剂量组、β-谷甾醇中剂量组和β-谷甾醇高剂量组,每组6只。除对照组小鼠外,其余各组小鼠建立雄黄诱导肝损伤模型,药物干预14 d后,苏木精-伊红(HE)染色检测肝组织损伤,检测肝功能指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST),ELISA检测血清炎症因子[肿瘤坏死因子(TNF-α)、白细胞介素1β(IL1-β)、IL-6]水平和肝组织氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)]水平,Western blot检测磷脂酰肌醇激酶3(PI3K)/蛋白激酶B(Akt)信号通路相关蛋白表达。另取12只小鼠按随机数字表法随机分为蛋白激酶B(AKt)激活剂(SC79)组和SC79+β-谷甾醇组,每组6只,采用PI3K/AKT通路激活剂SC79干预后检测上述相同指标。结果:与模型组比较,阳性对照组、β-谷甾醇中剂量组和β-谷甾醇高剂量组小鼠肝组织损伤均有不同程度改善,血清ALT、AST、TNF-α、IL1-β、IL-6、肝组织MDA水平均降低(P<0.05),肝组织SOD、GSH-Px升高(P<0.05),p-PI3K/PI3K、p-AKT/Akt、p-哺乳动物雷帕霉素靶蛋白(mTOR)/mTOR均降低(P<0.05),β-谷甾醇可逆转Akt激动剂SC79干预后上述指标变化的加剧(P<0.05)。结论:β-谷甾醇可改善雄黄诱导肝损伤小鼠肝功能,减轻肝脏炎性反应和氧化应激,对肝组织具有保护作用,其作用机制可能与抑制PI3K/Akt信号通路激活相关。Objective:To explore the effect and mechanism ofβ-sitosterol on realgar-induced liver injury in mice.Methods:The mice were divided into control group,model group,positive control group(bifendate),low-doseβ-sitosterol group,middle-doseβ-sitosterol group and high-doseβ-sitosterol group.Except for the control group,the other groups of mice established realgar-induced liver injury models.After 14 days of drug intervention,HE staining was used to detect the liver injury,and the liver function indicators Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)were detected.ELISA was applied to detect the levels of inflammatory factors[Tumor necrosis factor(TNF-α),Interleukin1β(IL1-β),IL-6],and kit was adopted to detect the liver tissue oxidative stress indicators[Malondialdehyde(MDA),Superoxide dismutase(SOD),Glutathione peroxidase(GSH-Px)].Western blot was used to detect the related protein expressions of PI3K/AKT signaling pathways.The above same indicators were detected after intervention with Phosphatidylinositol kinase 3(PI3K)/protein kinase B(Akt)pathways activator SC79.Results:Compared with the model group,the positive control group,the middle-doseβ-sitosterol group,and the high-doseβ-sitosterol group showed varying degrees of improvement in liver tissue damage in mice.Levels of serum ALT,AST,TNF-α,IL-1β,IL-6,and hepatic MDA were significantly reduced(P<0.05),while hepatic SOD and GSH-Px levels were significantly increased(P<0.05).Additionally,the ratios of p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR were significantly decreased(P<0.05).Furthermore,β-sitosterol was able to reverse the exacerbation of these indicators caused by intervention with the AKT agonist SC79(P<0.05).Conclusion:β-sitosterol inhibits the activation of PI3K/Akt signaling pathways to reduce serum inflammatory response and relieve oxidative stress in mice with realgar-induced liver injury,and it has a protective effect on liver tissue.

关 键 词：Β-谷甾醇 雄黄 肝损伤 PI3K/AKT信号通路 

分 类 号：R575.5[医药卫生—消化系统]