PI3K/AKT介导的凋亡信号通路在百草枯中毒致心脏损伤中的作用

目的探讨PI3K/AKT介导的凋亡信号通路在百草枯(PQ)中毒致心脏损伤中的作用。方法2019年7月—2020年1月于中国医科大学附属盛京医院本溪基地实验中心进行实验。选取健康成年雄性SD大鼠20只按随机数字表法均分为2组,百草枯中毒组(PQ组,10只)和对照组(10只)。百草枯中毒组大鼠予以一次性腹腔注射百草枯溶液20 mg/kg,对照组给予等量生理盐水。48 h后处死大鼠并心脏采血及收集心脏组织标本。HE染色观察2组大鼠心脏组织病理变化;检测2组大鼠血清CK、LDH水平,心脏组织SOD、MDA水平及PI3K、p-PI3K、AKT、p-AKT、Bcl2、Bax、Caspase-3相关蛋白的表达水平。结果与对照组比较,PQ组心脏结构完整性破坏,心脏损伤明显。PQ组血清CK及LDH水平明显高于对照组(t/P=67.304/0.001、33.619/0.001),且PQ组大鼠心肌组织中SOD水平下降,MDA水平显著升高(t/P=18.339/0.001、31.568/0.001)。PQ组大鼠在PQ暴露48 h后p-PI3K、p-AKT、Bcl-2表达水平明显下调(t/P=30.369/0.001、13.751/0.001、33.100/0.001),Bax、Caspase-3表达明显上调(t/P=13.765/0.001、12.649/0.001)。结论在百草枯中毒诱导心脏损伤中,PI3K/AKT介导的Bcl-2抗凋亡信号通路被抑制,进而导致促凋亡因子Bax和Caspase-3的表达上调,介导了心肌细胞的凋亡及心脏损伤。

The role of PI3K/AKT-mediated apoptosis signaling pathway in paraquat poisoning-induced cardiac injury

Objective To explore the role of PI3K/AKT-mediated apoptosis signaling pathway in paraquat(PQ)poisoning-induced heart damage.Methods From July 2019 to January 2020,the experiment was conducted at the Experimental Center of Benxi Base,Shengjing Hospital,China Medical University.Twenty healthy adult male SD rats were divided into 2 groups according to the random number table method,the paraquat poisoning group(PQ group,10)and the control group(10).The rats in the paraquat poisoning group were given a one-time intraperitoneal injection of 20 mg/kg of paraquat solution,and the control group was given the same amount of normal saline.After 48 hours,the rats were sacrificed and blood was collected from the heart and heart tissue samples were collected.HE staining was used to observe the pathological changes in the heart tissues of the two groups of rats.The levels of serum CK,LDH,SOD,MDA levels in the heart tissues and the expression of PI3K,p-PI3K,AKT,p-AKT,Bcl-2,Bax,Caspase-3 related proteins were detected Level.Results Compared with the control group,the integrity of the heart structure in the PQ group was damaged,and the heart injury was obvious.Serum CK and LDH levels in the PQ group were significantly higher than those in the control group(t/P=67.304/0.001,33.619/0.001),and the SOD level in the myocardial tissue of rats in the PQ group decreased,and the MDA level increased significantly(t/P=18.339/0.001,31.568/0.001).In the PQ group,the expression levels of p-PI3K,p-AKT,and Bcl-2 were significantly down-regulated(t/P=30.369/0.001,13.751/0.001,33.100/0.001),and the expressions of Bax and Caspase-3 were significantly up-regulated(t/P=13.765/0.001,12.649/0.001).Conclusion In paraquat poisoning-induced cardiac injury,the PI3K/AKT-mediated Bcl-2 anti-apoptotic signaling pathway is inhibited,which in turn leads to the up-regulation of the expression of pro-apoptotic factors Bax and Caspase-3,which mediate cardiomyocyte apoptosis and heart damage.