瑞芬太尼介导AMPKα1/PGC-1α/GLUT4通路对糖尿病动脉粥样硬化大鼠血脂和炎症的调节作用

Regulatory effects of remifentanil-mediated AMPKα1/PGC-1α/GLUT4 pathway on blood lipids and inflammation in rats with diabetic atherosclerosis

目的探讨瑞芬太尼(Rem)介导AMPKα1/PGC-1α/GLUT4通路对糖尿病动脉粥样硬化(AS)大鼠血脂和炎症的调节作用。方法将75只SD大鼠随机分为对照(NC)组15只和糖尿病模型(DM)组60只。NC组饲喂普通饲料,DM组饲喂高脂饲料,腹腔注射链脲佐菌素(40mg/kg)建立DM大鼠模型。将DM大鼠随机分为DM组和DM-Rem高中低剂量组各15只,Rem高中低剂量组分别经尾静脉泵注Rem 5 min(速率分别为1.6,0.8,0.4μg/kg/min)进行预处理,继续饲喂高脂饲料12周。采用生化分析仪分析血清中TC、TG、HDL及LDL水平;采用ELISA法测定血清中IL-6,IL-1β,iNOS,TNF-α水平;试剂盒检测LDH、MDA、SOD水平;TUNEL染色检测心肌组织凋亡;采用Western Blot检测ACC,SREBP-1c、CPT-1,PPARγ、Caspase-3、Caspase-9、AMPKα1、PGC-1α、GLUT4的表达。结果与DM组大鼠相比,DM-Rem高中低剂量组大鼠TC、TG、LDL、iNOS、IL-6、IL-1β和TNF-α水平均明显下降(P<0.05),ACC、SREBP-1c、Caspase-3和Caspase-9的表达明显下调(P<0.05),心肌组织凋亡率明显下降(P<0.05),且随着剂量升高其水平呈下降趋势,HDL水平明显升高(P<0.05),CPT-1、PPARγ、AMPKα1、PGC-1α和GLUT4表达均明显上调(P<0.05),且随着剂量升高其水平呈上升趋势。结论Rem可能通过调控AMPKα1/PGC-1α/GLUT4信号通路的表达,降低糖尿病AS大鼠血脂和炎症因子水平,保护心肌组织损伤。

Objective To explore the regulatory effects of remifenil(Rem)-mediated AMPKα1/PGC-1α/GLUT4 pathway on blood lipids and inflammation in rates with diabetic atherosclerosis(AS).Methods 75 SD rats were randomly divided into control group(NC,15 rats)and diabetic model group(DM,60 rats).NC group was fed with normal diet,and DM group was fed with high-fat diet,and the DM rat model was established by intraperitoneal injection of streptozotocin(40 mg/kg).DM rats were randomly divided into DM group and high dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups,with 15 rats in each group.High dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups were pumped with Rem for 5 min via tail vein for preprocessing(at rates of 1.6,0.8 and 0.4μg/kg/min respectively),and were fed with high-fat diet for 12 w.The levels of TC,TG,HDL and LDL in serum were analyzed by biochemical analyzer.The levels of IL-6,IL-1β,iNOS and TNF-α in serum were determined by ELISA.The levels of LDH,MDA and SOD were detected by kit.Apoptosis of myocardial tissues was detected by TUNEL staining.Western Blot was used to detect the expression levels of ACC,SREBP-1 c,CPT-1,PPARγ,Caspase-3,Caspase-9,AMPKα1,PGC-1α and GLUT4.Results Compared with DM group,the levels of TC,TG,LDL,iNOS,IL-6,IL-1β and TNF-α in high dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups were significantly decreased(P<0.05),the expression levels of ACC,SREBP-1 c,Caspase-3 and Caspase-9 in high dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups were significantly down-regulated(P<0.05),the apoptosis rate of myocardial tissues in high dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups was significantly decreased(P<0.05),HDL level in high dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups was increased significantly(P<0.05),the expression levels of CPT-1,PPARγ,AMPKα1,PGC-1α and GLUT4 in high dose DM-Rem groups,medium dose DM-Rem groups and low dose DM-Rem groups were significantly up-regulated(P<0.05).Conclusion Rem may lower blood lipids and inflammatory factors and protect myocardial tissue damage by regulating the expression of AMPKα1/PGC-1α/GLUT4 signaling pathway.