老鼠簕生物碱A对肝纤维化大鼠PI3K/Akt/m TOR/p70S6K信号通路的影响

Effect of Acanthus ilicifolius alkaloid A on PI3K/Akt/mTOR/p70S6K signaling pathway in rats with hepatic fibrosis

目的观察老鼠簕生物碱A(HBOA)对四氯化碳(CCl4)致肝纤维化大鼠磷酸肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(m TOR)/p70核糖体蛋白S6激酶(p70S6K)信号通路的影响,探讨HBOA抗肝纤维化的作用机制。方法大鼠随机分成对照组、模型组及HBOA高、中、低剂量(100、50、25 mg/kg)组和秋水仙碱(0.4 mg/kg)组。除对照组外,其余各组ig给予50%CCl4橄榄油溶液,每周2次,连续12周,诱导肝纤维化大鼠模型。于造模第9周起,给药组分别ig相应的受试药物,每天1次,给药4周。实验结束后,计算各组大鼠体质量变化、肝脏指数;检测各组大鼠肝匀浆中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性;蛋白免疫印迹法(Western blotting)法检测肝组织P-PI3K、p-Akt、p-mTOR、p-p70S6K蛋白的表达。结果与模型组比较,各给药组大鼠体质量增加量显著升高,均能降低肝脏指数及肝组织中ALT、AST活性;此外,HBOA高、中剂量组均能显著抑制p-PI3K、p-Akt、p-m TOR、p-p70S6K蛋白的表达。结论 HBOA对肝纤维化大鼠具有一定的保护作用,其机制可能与抑制PI3K/Akt/m TOR/p70S6K信号通路有关。

Objective To observe the effect of Acanthus ilicifolius alkaloid A(HBOA) on PI3 K/AKT/m TOR/p70S6K signaling pathway in rats with hepatic fibrosis induced by carbon tetrachloride(CCl4),and to explore the mechanism of action of HBOA against liver fibrosis.Methods Rats were randomly divided into normal group,model group,high,medium;and low-dose HBOA groups(100,50,25 mg/kg),and colchicine group(0.4 mg/kg).Except for the normal group,the rats in other groups were given with a 50% CCl4 olive oil solution twice a week for 12 weeks to induce a rat model of liver fibrosis.From the ninth week of modeling,the drug-administered group was given the corresponding test drug once daily for 4 weeks.After the experiment,the body mass change and liver index were calculated.The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver homogenate of each group were detected.The protein expression of p-PI3 K,p-Akt,p-mTOR,and p-p70S6K in liver tissue was detected by Western blotting.Results Compared with the model group,the body weight of mice of each drug-administered group was significantly increased,and the liver index,and ALT and AST levels were decreased in liver tissue.In addition,HBOA high and medium-dose groups significantly inhibited the protein expression of p-PI3K,p-Akt,p-mTOR,and p-p70S6K.Conclusion HBOA has a protective effect on hepatic fibrosis rats,and its mechanism may be related to the inhibition of PI3K/Akt/mTOR/p70S6K signaling pathway.