摘要
【目的】探讨肉桂醛通过调节腺苷酸活化蛋白激酶(AMPK)/胆固醇调节元件结合蛋白1c(SREBP1c)信号通路对非酒精性脂肪性肝炎(NASH)小鼠肝损伤的影响。【方法】实验随机分为正常组,模型组,肉桂醛低、中、高剂量组及肉桂醛高剂量+Compound C(AMPK抑制剂)组,每组15只小鼠。除正常组,其他各组给予高脂饲料喂养构建NASH模型。干预治疗后,观察肝组织病理形态变化,检测血清生化指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(TC)],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(GSH)],AMPK/SREBP1c通路蛋白[磷酸化AMPK(p-AMPK)、AMPK、SREBP1c、乙酰辅酶A羧化酶(ACC)、磷酸化ACC(p-ACC)、肉毒碱棕榈酰转移酶1(CPT1)、硬脂酰辅酶A去饱和酶1(Scd1)]表达,及CPT1α、长链酯酰辅酶A脱氢酶(Lcad)、ACC1、脂肪酸合成酶(FAS)的mRNA表达水平。【结果】与正常组比较,模型组肝脏脂肪变性,脂质沉积和纤维化间质增多,ALT、AST、TG、TC,MDA含量,SREBP1c、Scd1蛋白表达,ACC1、FAS mRNA表达水平显著升高,SOD、GSH活性,p-AMPK、AMPK、p-ACC、ACC、CPT1蛋白表达,CPT1α、Lcad m RNA表达水平显著降低(P<0.05);与模型组比较,肉桂醛低、中、高剂量组脂质沉积和纤维化间质减少,ALT、AST、TG、TC、MDA含量,SREBP1c、Scd1蛋白表达,ACC1、FAS mRNA表达水平显著降低,SOD、GSH活性,p-AMPK、AMPK、p-ACC、ACC、CPT1蛋白表达,CPT1α、Lcad mRNA表达水平显著升高(P<0.05),且呈剂量依赖性;与肉桂醛高剂量组比较,肉桂醛高剂量+Compound C组上述指标均被逆转(P<0.05)。【结论】肉桂醛可能通过调控AMPK/SREBP1c通路,抑制氧化应激,改善肝脏脂肪变性,减轻NASH小鼠肝损伤。
Objective To investigate the effect of cinnamyl aldehyde on liver injury in non-alcoholic steatohepatitis(NASH)mice by modulating the AMP-activated protein kinase(AMPK)/sterol regulatory element-binding protein 1c(SREBP1c)signalling pathway.Methods The experiment was randomly divided into normal group,model group,cinnamaldehyde low-,medium-and high-dose group and cinnamyl aldehyde high-dose+Compound C(AMPK inhibitor)group,with 15 mice in each group.Except for the normal group,all other groups were given high-fat chow to construct the NASH model.After the intervention treatment,the pathomorphological changes of liver tissue were observed,and the serum biochemical indexes[alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)],oxidative stress indexes of liver tissueprotein[phosphorylated AMPK(p-AMPK),AMPK,SREBP1c,acetyl coenzyme A carboxylase(ACC),phosphorylated ACC(p-ACC),carnitine palmitoyltransferase 1(CPT1),stearoyl coenzyme A desaturase 1(Scd1)]expressions,and the mRNA expression levels of CPT1α,long chain esteroyl coenzyme A dehydrogenase(Lcad),ACC1,fatty acid synthase(FAS)were detected.Results Compared with the normal group,hepatic steatosis,increased lipid deposition and fibrotic interstitium,ALT,AST,TG,TC,MDA content,protein expressions of SREBP1c,Scd1,mRNA expression levels of ACC1,FAS were significantly increased,protein expressions of SOD,GSH activity,p-AMPK,AMPK,p-ACC,ACC,CPT1 in the model group,and mRNA expression levels of CPT1αand Lcad were significantly reduced(P<0.05);compared with the model group,cinnamyl aldehyde low-,medium-and high-dose groups showed a reduction in lipid deposition and fibrotic mesenchyme,ALT,AST,TG,TC,MDA content,SREBP1c,Scd1 protein expression,mRNA expression levels of ACC1 and FAS were significantly reduced;SOD,GSH activity,and protein expressions of the p-AMPK,AMPK,p-ACC,ACC,CPT1,mRNA expression levels of CPT1α,Lcad were significantly increased(P<0.05),and in a dose-dependent manner;compared with the cinnamyl aldehyde high-dose group,all of the above indexes in the cinnamyl aldehyde high-dose+Compound C group were reversed(P<0.05).Conclusion Cinnamyl aldehyde may inhibit oxidative stress,improve hepatic steatosis and attenuate liver injury in NASH mice by regulating the AMPK/SREBP1c pathway.
作者
姚硕
李源
段超
曾艳
YAO Shuo;LI Yuan;DUAN Chao;ZENG Yan(Dept.of Integrated Chinese and Western Medicines,Liyuan Hospital of Tongji Medical College of Huazhong University of Science&Technology,Wuhan 430077 Hubei,China;Dept.of Hematology,Liyuan Hospital of Tongji Medical College of Huazhong University of Science&Technology,Wuhan 430077 Hubei,China)
出处
《广州中医药大学学报》
CAS
2024年第2期438-447,共10页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
湖北省中医药科研立项项目(编号:ZY2023F036)。
作者简介
姚硕(1982-),男,硕士,主治医师,E-mail:lalenax@163.com;通信作者:曾艳(1980-),女,硕士,副主任医师,E-mail:qusuanchaon6@163.com。
