摘要
目的探讨玉郎伞查尔酮(YLSC)调控PI3K/Akt信号通路抗心肌缺血/再灌注损伤的作用及机制。方法 40只♂SD大鼠随机分为5组:假手术组、模型组、YLSC组、YLSC+PI3K抑制剂wortmannin组(YLSC+WM组)、PI3K抑制剂wortmannin组(WM组),每组8只。除假手术组外,其它各组大鼠均结扎冠状动脉左前降支制备心肌缺血模型,缺血30 min,再灌注120 min。实验结束后,采用比色法测定大鼠血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)及一氧化氮(NO)水平,ELISA法测定血清肿瘤坏死因子(TNF-α)的含量,Western blot法检测心肌组织中总Akt(t-Akt)、磷酸化Akt(p-Akt)及自噬相关蛋白LC3-Ⅱ的表达,FQ-PCR法分析内皮型一氧化氮合酶(eN OS)、凋亡因子caspase-3及自噬相关基因Beclin1的表达量变化。结果与I/R组比较,YLSC组CK-MB、LDH以及TNF-α血清含量明显降低,NO水平升高,Beclin1、caspase-3及LC3-Ⅱ的表达量均明显下降,同时Akt的磷酸化水平与eN OS mR NA表达增加,上述各项指标差异具有统计学意义(P<0.05),而上述变化能够被PI3K/Akt信号通路的特异性阻断剂wortmannin所阻断,且其差异具有统计学意义(P<0.05)。结论 YLSC通过激活PI3K/Akt信号通路抑制缺血/再灌注所致的心肌细胞凋亡和过度自噬,从而发挥对心肌缺血/再灌注损伤的保护作用。
Aim To investigate the effects of 17-methoxyl-7-hydroxyl-benzofuran chalcone( YLSC) on myocardial ischemia / reperfusion injury( MI / RI) by modulating PI3 K / Akt signaling pathway and the possible mechanisms. Methods Male SD rats were randomly divided into sham group,model group,YLSC group,wortmannin( WM) group and YLSC + WM group( n =8). The rat model of MI / RI was established by ligation of the left anterior descending artery for 30 min followed by loosening the ligature for 2 h. After reperfusion,blood samples were obtained to determine serum contents of CK-MB,LDH,NO and TNF-α. The protein levels of total( t)-Akt,phosphorylated( p)-Akt and LC3-Ⅱ were detected by Western blot. Caspase-3,Beclin1 and e NOS mR NA expression was evaluated by FQ-PCR. Results YLSC pretreatment greatly reduced serum levels of CK-MB,LDH and TNF-α,and elevated NO content. It also inhibited the expression of caspase-3,Beclin1 and LC3-Ⅱ,while enhanced pAkt and e NOS expression. Conclusion YLSC protects the heart against MI / RI via inhibition of apoptosis and excessive autophagy,in which protective effect is regulated by activation of the PI3 K / Akt pathway.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2015年第12期1730-1735,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81160533)
广西科技基础条件平台建设项目(No 12-97-20)
广西研究生创新课题(No YCSZ2014104)
关键词
玉郎伞查尔酮
调控
PI3K/AKT
凋亡
自噬
心肌缺血/再灌注损伤
17-methoxyl-7-hydroxyl-benzofuran chalcone
regulation
PI3K/Akt
apoptosis
autophagy
myocardial ischemia/reperfusion injury
