文章摘要
赵 喜,王小蓉,程金妹,陈爱春.二苯乙烯苷经 PPAR α信号通路激活自噬治疗大鼠高脂性脂肪肝的作用研究[J].南京医科大学学报,2018,(12):1679~1682,1687
二苯乙烯苷经 PPAR α信号通路激活自噬治疗大鼠高脂性脂肪肝的作用研究
Therapeutic effect of 2,3,4’,5⁃tetrahydroxystilbene⁃2⁃O⁃β⁃D⁃glucoside on hyperlipidemic fatty liver in rats by activating PPAR α pathway of autophagy
投稿时间:2018-08-13  
DOI:10.7655/NYDXBNS20181203
中文关键词: 二苯乙烯苷  高脂性脂肪肝  PPAR α  自噬
英文关键词: 2,3,4’,5⁃tetrahydroxystilbene⁃2⁃O⁃β⁃D⁃glucoside  hyperlipidemic fatty liver  peroxisome proliferator⁃activated recep⁃ tor α  autophagy
基金项目:国家自然科学基金(81202879)
作者单位
赵 喜 南通大学医学院生殖医学研究院江苏 南通 226001 
王小蓉 南通大学医学院生殖医学研究院江苏 南通 226001 
程金妹 南通大学医学院生殖医学研究院江苏 南通 226001 
陈爱春 南通大学医学院生殖医学研究院江苏 南通 226001 
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中文摘要:
      目的:观察二苯乙烯苷(TSG)对高脂性脂肪肝大鼠的治疗作用,并从PPAR α信号通路研究其可能的作用机制。方法:将雄性SD大鼠随机分为正常组、模型组、TSG(80 mg/kg)组、MK886+ TSG(80 mg/kg)组。采用高脂饮食建立大鼠高脂性脂肪肝模型,给予二苯乙烯苷治疗6周,然后测定血清和肝组织中总胆固醇(TC)、甘油三酯(TG)和游离脂肪酸(FFA)水平,测定肝重系数及血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平;光镜检查肝脏的病理形态学改变。同时采用Western blot法检测各组大鼠肝脏中过氧化物酶体增殖物激活受体α(PPAR α)、自噬相关蛋白LC3Ⅰ、LC3Ⅱ、Beclin 1及p62的表达情况。结果:与模型组相比,TSG给药6周后,能显著降低脂肪肝大鼠血清中TC、TG和FFA水平,肝组织中TG、FFA含量和肝重系数,及血清中ALT和AST水平(P<0.05或P<0.01);同时病理检查结果显示,TSG给药组大鼠肝组织脂肪变性明显减轻。Western blot检测结果显示,TSG可明显上调肝组织中PPAR α蛋白的表达,上调LC3Ⅱ、Beclin 1蛋白的表达,并下调p62的表达(P<0.01)。当预先使用PPAR α拮抗剂MK886时,TSG的作用明显减弱或消失。结论:TSG对高脂性脂肪肝大鼠具有明显的治疗作用,其机制可能与通过激活PPAR α后,上调LC3Ⅱ、Beclin 1和下调p62的蛋白表达而激活细胞自噬,从而促进脂滴的降解,改善肝脏脂质代谢紊乱有关。
英文摘要:
      Objective:To observe the effect of 2,3,4’,5?tetrahydroxystilbene?2?O?β?D?glucoside (TSG) on hyperlipidemic fatty liver in rats,and explore the potential mechanisms by PPAR α signaling pathway. Methods:SD rats were randomly divided into control group,model group,TSG 80 mg/kg group,MK886 plus TSG 80 mg/kg group. The rat model was established by orally feeding high?fat emulsion for 4 weeks. Then TSG was administered to these rats for 6 weeks. TC,TG and FFA levels in serum and hepatic tissues,hepatic weight coefficient,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were measured;and the hepatic histopathological changes were observed. Meanwhile,the expressions of PPAR α,LC3Ⅰ,LC3Ⅱ,Beclin 1 and p62 proteins in hepatic tissues were measured by Western blot. Results:Compared with the model group,TSG could significantly decrease TC,TG and FFA levels in serum,TG and FFA contents in hepatic tissues,hepatic weight coefficient,and also the serum levels of ALT and AST(P<0.05 or P<0.01). Meanwhile,the histological evaluation of liver specimens revealed that lipid accumulation in TSG?treated group was obviously ameliorated. Western blot results showed that TSG could markedly up?regulated the expressions of hepatic PPAR α,LC3Ⅱ,Beclin 1 proteins,and down?regulated the expression of p62(P<0.05 or P<0.01). However,the effect of TSG was weakened or cancelled when pretreatment with PPAR α antagonist MK886. Conclusion:TSG was effective in treating hyperlipidemic fatty liver in rats,and its mechanism might be related to the up?regulation of LC3Ⅱ and Beclin 1 protein expressions,down?regulation of p62 protein expression to activate autophagy by activation of PPAR α,and eventually to improve lipid metabolism.
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