三肽脯氨酸对大鼠蛛网膜下腔出血后脑神经细胞凋亡的影响  

Tristetraprolin attenuates subarachnoid hemorrhage-induced apoptosis in rats

作　　者：陈朝晖[1] 洪溪屏[1] 兰频[1] 潘锋[1] CHEN Chaohui;HONG Xiping;LAN Pin;PAN Feng(Department of Emergency,Lishui Central Hospital,Lishui 323000,China)

机构地区：[1]丽水市中心医院急诊科,323000

出　　处：《浙江医学》2018年第14期1562-1566,共5页Zhejiang Medical Journal

摘　　要：目的探讨三肽脯氨酸(TTP)对大鼠蛛网膜下腔出血(SAH)后脑神经细胞凋亡的影响及其机制。方法将120只成年雄性SD大鼠随机分为8组,假手术(Sham)组、模型(SAH)组、TTP过表达对照(SAH+Vector)组、TTP过表达(SAH+TTP)组、TTP干扰对照(SAH+NC)组、TTP小干扰(SAH+siTTP)组、AMPK通路激动剂AICAR(SAH+AICAR)组和SAH+AICAR+TTP组,每组15只,采用血管内穿刺法建立SAH模型,SAH造模24h后应用Tunel法检测各组大鼠脑神经细胞凋亡率,Western blot法检测脑组织中TTP、Bax、Bcl-2、Caspase-3、p-AMPK和p-LKB1的表达。结果与Sham组比较,SAH组大鼠脑神经细胞凋亡率明显上升,Bax、Caspase-3、p-AMPK和p-LKB1的表达上调,而Bcl-2的表达下调;与SAH+Vector组比较,SAH+TTP组大鼠脑神经细胞凋亡率显著下降,Bax、Caspase-3、p-AMPK和p-LKB1的表达下调,而Bcl-2的表达上调;与SAH+NC组比较,SAH+siTTP组大鼠脑神经细胞凋亡率显著上升,Bax和Caspase-3的表达上调,而Bcl-2的表达下调;与SAH+TTP组比较,SAH+AICAR+TTP组中p-AMPK和Caspase-3的表达明显上调。结论 TTP可减轻大鼠SAH后脑神经细胞的凋亡,抑制AMPK通路可能是其主要机制。Objective To explore the effect of tristetraprolin(TTP)on the apoptosis following subarachnoid hemorrhage(SAH)in rats. Methods One hundred and twenty SD rats were divided into 8 groups:Sham group,SAH group,SAH+vector group,SAH+TTP group,SAH+NC group,SAH+siTTP group,AMPK activator(SAH+AICAR)group and SAH+AICAR+TTP group.The SAH model was induced by endovascular perforation method.The neuronal apoptosis in rat brain tissue was detected by TUNEL staining.The expression of TTP,Bax,Bcl-2,Caspase-3,p-AMPK and p-LKB1 in rat brain tissue were detected by western blot. Results Compared with the Sham group,the neuronal apoptosis in SAH group was significantly enhanced,and the expression levels of Bax,Caspase-3,p-AMPK and p-LKB1 were significantly increased,while the expression of Bcl-2 was decreased.Overexpression of TTP significantly reduced the number of TUNEL positive cells,while there was a higher apoptotic rate in brain tissues with siRNA administration.Furthermore,upregulation of TTP significantly decreased the expression levels of Caspase-3,Bax,p-AMPK as well as p-LKB1,and enhanced the expression of Bcl-2.In addition,siTTP reduced the Bcl-2 expression,and increased the expression of Caspase-3 and Bax,compared to the SAH+NC group.Compared to SAH+TTP group the expression of p-AMPK and Caspase-3 in SAH+AICAR+TTP group was significantly upregulated. Conclusion The upregulation of TTP can effectively inhibit apoptosis following SAH in rats,and the protective effect is mediated by AMPK pathway inhibition.The results indicate that TTP may serve as a promising therapeutic target for SAH treatment.

关 键 词：三肽脯氨酸 蛛网膜下腔出血 凋亡 AMP激活的蛋白激酶 

分 类 号：R743.35[医药卫生—神经病学与精神病学]