阿芬太尼对糖尿病大鼠心肌缺血再灌注损伤及VEGFA/Ang-1通路的影响

Effects of Alfentanil on Myocardial Ischemia-reperfusion Injury and VEGFA/Ang-1 Pathway in Diabetic Rats

目的:探讨阿芬太尼对糖尿病大鼠心肌缺血/再灌注(I/R)损伤及血管内皮生长因子A(VEGFA)/血管紧张素-1(Ang^(-1))通路的影响。方法:用链脲佐菌素(60 mg·kg^(-1))腹腔注射的方法制备大鼠糖尿病模型,造模成功后制备I/R模型。将造模成功的Wistar大鼠随机分为假手术组、I/R组、吗啡组(0.1 mg·kg^(-1))和阿芬太尼低、高剂量组(3,6 mg·kg^(-1)),每组10只。在结扎前30 min,阿芬太尼低、高剂量组和吗啡组尾静脉注射相应剂量药物,假手术组和I/R组尾静脉注射等量生理盐水。再灌注2 h,对大鼠进行心功能检测,处死大鼠,检测血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、丙二醛(MDA)和超氧化物歧化酶(SOD)水平;检测心肌组织中VEGFA、Ang^(-1)和半胱氨酸天冬氨酸蛋白酶-3(caspase-3)蛋白水平。结果:与假手术组比较,其余各组大鼠左心室舒张压(LVDP)、血清中SOD、心肌组织中VEGFA和Ang^(-1)蛋白水平降低,左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、血清中CK-MB、LDH、MDA和心肌组织中caspase-3水平升高(P<0.05)。与I/R组比较,阿芬太尼低、高剂量组和吗啡组大鼠LVDP、血清中SOD、心肌组织中VEGFA和Ang^(-1)蛋白水平升高,LVEDD、LVESD、血清中CK-MB、LDH、MDA和心肌组织中caspase-3水平降低(P<0.05)。阿芬太尼低剂量组与高剂量组、吗啡组比较,以上各指标差异有统计学意义(P<0.05);阿芬太尼高剂量组和吗啡组作用相似,差异无统计学意义(P>0.05)。结论:阿芬太尼可以激活VEGFA/Ang^(-1)通路,降低caspase-3水平,对糖尿病大鼠心肌I/R损伤发挥保护作用。

Objective:To investigate the effects of alfentanil on myocardial ischemia/reperfusion(I/R)injury and vascular endothelial growth factor A(VEGFA)/angiotensin-1(Ang^(-1))pathway in diabetic rats.Methods:The rat diabetes model was made by intraperitoneal injection of streptozotocin(60 mg·kg^(-1)),and the I/R model was prepared after successful modeling.Wistar rats were randomly divided into sham operation group,I/R group,morphine group(0.1 mg·kg^(-1)),alfentanil low and high dose groups(3 and6 mg·kg^(-1))with 10 rats in each group.At 30 minutes before ligation,morphine group,alfentanil low and high dose groups were injected with corresponding dose of drug,and the sham operation group and I/R group were injected with the same amount of normal saline via tail vein.After 2 hours of reperfusion,the rats were tested for cardiac function,and then the rats were sacrificed.The serum levels of creatine kinase isoenzymes(CK-MB),lactic dehydrogenase(LDH),malondialdehyde(MDA)and superoxide dismutase(SOD)were detected,and the levels of VEGFA,Ang^(-1)and cysteinyl aspartate specific proteinase-3(caspase-3)protein in myocardial tissue were also detected.Results:Compared with those in the sham operation group,the levels of left ventricular diastolic pressure(LVDP),serum SOD,myocardial tissue VEGFA and Ang^(-1)in the other groups were decreased,and the levels of left ventricular end diastolic diameter(LVEDD),left ventricular endsystolic diameter(LVESD),serum CK-MB,LDH and MDA,and myocardial tissue caspase-3 were increased(P<0.05).Compared with those in I/R group,the levels of LVDP,serum SOD,myocardial tissue VEGFA and Ang^(-1)in the low dose alfentanil group,high dose alfentanil group and morphine group were increased,and the levels of LVEDD,LVESD,serum CK-MB,LDH and MDA,and myocardial tissue caspase-3 were decreased(P<0.05).Compared with those in alfentanil high dose group and morphine group,the above indicators had statistically significant differences in alfentanil low dose group(P<0.05);alfentanil high dose group and morphine group had similar effects,and there were no statistically significant differences(P>0.05).Conclusion:Alfentanil can reduce the level of Caspase-3 by activating VEGFA/Ang^(-1)pathway,which plays a protective effect on myocardial I/R injury in diabetic rats.