高频率超声影像评价kv7钾离子通道对感染性休克大鼠左心室功能的影响
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摘要
目的采用高频率超声影像评价kv7钾离子通道对感染性休克大鼠左心室功能的影响。方法选取雄性200～250g SD大鼠采用盲肠结扎穿孔法制备大鼠感染性休克模型,术后随机分为模型组和kv7钾离子通道阻断剂XE991高、中、低剂量组(n=20),XE991高、中、低剂量组术后经股静脉持续输注5、10、20μmol/kg XE991。同时选取20只仅行开腹而不行结扎大鼠作为假手术组,假手术组和模型组术后经股静脉持续输注生理盐水。采用超高分辨力小动物超声影像系统三维成像技术进行超声心动图检查术后72h大鼠的左心室功能指标;检测术后72h大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、丙二醛(MDA)和超氧化物歧化酶(SOD)水平及心肌组织中肿瘤坏死因子(TNF-α)和白细胞介素-1β(IL-1β)水平。结果与假手术组比较,模型组大鼠左心室功能指标LVEDV、LVESV、血清CK、LDH和MDA水平及心肌组织TNF-α、IL-1β水平均升高,而EF、FS和SV及血清SOD水平均降低,差异有统计学意义(P<0.05);输注XE991高、中、低剂量组的LVEDV、LVESV、血清CK、LDH和MDA水平及心肌组织TNF-α、IL-1β水平均低于模型组,EF、FS和SV及血清SOD水平均高于模型组(P<0.05)。且XE991高剂量组指标均优于中、低剂量组(P<0.05)。结论高频率超声影像可有效评价阻断kv7钾离子通道对感染性休克大鼠左心室功能的改善作用,可能与减轻心肌损伤、氧化应激及炎症反应有关,且该改善作用与XE991剂量有关。
OBJECTIVE To evaluate the effect of Kv7 potassium channel on left ventricular function of septic shock rats by high frequency ultrasound imaging.METHODS The male SD rats weighing between 200 and 250 g were selected to prepare septic shock models by cecal ligation and puncture.After operation,the rats were randomly divided into the model group and the high-,medium-and low-dose of Kv7 potassium channel blocker XE991 groups and were continuously injected 5,10 and 20μmol/kg XE991 via femoral vein after operation.Meanwhile,20 rats that only received laparotomy and were not treated with ligation were chosen as the sham group.The rats in the sham group and model group were continuously transfused normal saline through femoral vein after operation.The left ventricular function indexes were detected by using ultra-high resolution small animal ultrasound imaging system three-dimensional imaging technology after echocardiography for 72 hours;the related kits were employed to measure the levels of serum lactate dehydrogenase(LDH),creatine kinase(CK),malondialdehyde(MDA)and superoxide dismutase(SOD)as well as the levels of tumor necrosis factor-a(TNF-a)and interleukin-1β(IL-1β)in myocardial tissues after the surgery for 72 hours.RESULTS The levels of LVEDV,LVESV,CK,LDH,MDA,TNF-αand IL-1βof the model group were higher than those of the sham surgery group,while the levels of EF,FS,SV and SOD of the model group were lower than those of the sham surgery group,and there were significant differences(P<0.05).The levels of LVEDV,LVESV,CK,LDH,MDA,TNF-αand IL-1βof the high-,medium-and low-dose XE991 groups were significantly lower than those of the model group(P<0.05),and the levels of the above indexes of the high-dose XE991 group were significantly better than those of the medium-and low-dose groups(P <0.05).CONCLUSION The high frequency ultrasound imaging can effectively evaluate the effect of blocking Kv7 potassium channel on improvement of left ventricular function of the septic shock rats,it may be related to the reduction of myocardial injury,oxidative stress and inflammatory response,and the effect of this improvement is related to the dose of XE991.
OBJECTIVE To evaluate the effect of Kv7 potassium channel on left ventricular function of septic shock rats by high frequency ultrasound imaging.METHODS The male SD rats weighing between 200 and 250 g were selected to prepare septic shock models by cecal ligation and puncture.After operation,the rats were randomly divided into the model group and the high-,medium-and low-dose of Kv7 potassium channel blocker XE991 groups and were continuously injected 5,10 and 20μmol/kg XE991 via femoral vein after operation.Meanwhile,20 rats that only received laparotomy and were not treated with ligation were chosen as the sham group.The rats in the sham group and model group were continuously transfused normal saline through femoral vein after operation.The left ventricular function indexes were detected by using ultra-high resolution small animal ultrasound imaging system three-dimensional imaging technology after echocardiography for 72 hours;the related kits were employed to measure the levels of serum lactate dehydrogenase(LDH),creatine kinase(CK),malondialdehyde(MDA)and superoxide dismutase(SOD)as well as the levels of tumor necrosis factor-a(TNF-a)and interleukin-1β(IL-1β)in myocardial tissues after the surgery for 72 hours.RESULTS The levels of LVEDV,LVESV,CK,LDH,MDA,TNF-αand IL-1βof the model group were higher than those of the sham surgery group,while the levels of EF,FS,SV and SOD of the model group were lower than those of the sham surgery group,and there were significant differences(P<0.05).The levels of LVEDV,LVESV,CK,LDH,MDA,TNF-αand IL-1βof the high-,medium-and low-dose XE991 groups were significantly lower than those of the model group(P<0.05),and the levels of the above indexes of the high-dose XE991 group were significantly better than those of the medium-and low-dose groups(P <0.05).CONCLUSION The high frequency ultrasound imaging can effectively evaluate the effect of blocking Kv7 potassium channel on improvement of left ventricular function of the septic shock rats,it may be related to the reduction of myocardial injury,oxidative stress and inflammatory response,and the effect of this improvement is related to the dose of XE991.
引文
[1]马颖,季萍,张朝霞,等.降钙素原与超敏C-反应蛋白和N末端前体脑钠肽对脓毒症预后的评估价值[J].中华医院感染学杂志,2016,26(10):2245-2247.
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[12]Moralescano D,Moreno L,Barreira B,et al.Activation of PPARβ/δprevents hyperglycemia-induced impairment of Kv7channels and cAMP-mediated relaxation in rat coronary arteries[J].Clin Sci(Lond),2016,130(20):1823-1836.
[13]Fosmo AL,Oyvind B.Skraastad.The Kv7channel and cardiovascular risk factors[J].Front Cardiovasc Med,2017,4:75.
[14]Trotta MC,Salerno M,Brigida AL,et al.Inhibition of aldose-reductase-2by a benzofuroxane derivative bf-5mincreases the expression of kcne1,kcnq1in high glucose cultured H9c2cardiac cells and sudden cardiac death[J].Oncotarget,2017,9(25):17257-17269.
[15]Oliveras A,Roura-Ferrer M,Sole L,et al.Functional assembly of Kv7.1/Kv7.5channels with emerging properties on vascular muscle physiology[J].Arterioscler Thromb Vasc Biol,2014,34(7):1522-1530.
[16]Liu H,Jia L,Chen X,et al.The Kv7/KCNQ channel blocker XE991 protects nigral dopaminergic neurons in the 6-hydroxydopamine rat model of Parkinson's disease[J].Brain Res Bull,2018,137:132-139.
[17]Bernardoseisdedos G,Nunez E,Gomisperez C,et al.Structural basis and energy landscape for the Ca2+gating and calmodulation of the Kv7.2K+channel[J].Proc Natl Acad Sci U SA,2018,115(10):2395-2400.
[18]Telezhkin V,Straccia M,Yarova P,et al.Kv7channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons[J].Pflugers Arch,2018,470(9):1-18.
[19]Bodor GS.Biochemical markers of myocardial damage[J].EJIF-CC,2016,27(2):95-111.
[20]Tzour A,Leibovich H,Barkai O,et al.KV7/M channels as targets for lipopolysaccharide‐induced inflammatory neuronal hyperexcitability[J].J Physiol,2016,595(3):713-718.
[2]Kellum JA,Chawla LS,Keener C,et al.The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock[J].Am J Respir Crit Care Med,2016,193(3):281-287.
[3]李江,贾宝辉,宋佳丽.PLB小干扰RNA对感染性休克大鼠左心功能的作用[J].中华医院感染学杂志,2017,27(14):3184-3187.
[4]程火星,谢庆.肌钙蛋白I和脑利钠肽联合检测在感染性休克相关心肌损伤诊治中的应用[J].河北医药,2016,38(7):1013-1015.
[5]Greene DL,Hoshi N.Modulation of Kv7channels and excitability in the brain[J].Cell Mol Life Sci,2016,74(3):1-14.
[6]Testai L,Barrese V,Soldovieri MV,et al.Expression and function of Kv7.4channels in rat cardiac mitochondria:possible targets for cardioprotection[J].Cardiovasc Res,2016,110(1):40-50.
[7]Hedegaard ER,Johnsen J,Povlsen JA,et al.Inhibition of KV7channels protects the rat heart against myocardial ischemia and reperfusion injury[J].J Pharmacol Exp Ther,2016,357(1):94-102.
[8]Stott JB,Barrese V,Greenwood IA.Kv7channel activation underpins EPAC-dependent relaxations of rat arteries[J].Arterioscler Thromb Vasc Biol,2016,36(12):2404-2411.
[9]Irani SR,Vincent A.Voltage-gated potassium channel-complex autoimmunity and associated clinical syndromes[J].Handb Clin Neurol,2016,133:185-197.
[10]Wagner J,Schoenebake JC,Witt JA,et al.Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis[J].Epilepsia,2016,57(3):475-483.
[11]Lombardo J,Harrington MA.Non-reciprocal mechanisms of up-and down-regulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels[J].J Neurophysiol,2016,116(5):2114-2124.
[12]Moralescano D,Moreno L,Barreira B,et al.Activation of PPARβ/δprevents hyperglycemia-induced impairment of Kv7channels and cAMP-mediated relaxation in rat coronary arteries[J].Clin Sci(Lond),2016,130(20):1823-1836.
[13]Fosmo AL,Oyvind B.Skraastad.The Kv7channel and cardiovascular risk factors[J].Front Cardiovasc Med,2017,4:75.
[14]Trotta MC,Salerno M,Brigida AL,et al.Inhibition of aldose-reductase-2by a benzofuroxane derivative bf-5mincreases the expression of kcne1,kcnq1in high glucose cultured H9c2cardiac cells and sudden cardiac death[J].Oncotarget,2017,9(25):17257-17269.
[15]Oliveras A,Roura-Ferrer M,Sole L,et al.Functional assembly of Kv7.1/Kv7.5channels with emerging properties on vascular muscle physiology[J].Arterioscler Thromb Vasc Biol,2014,34(7):1522-1530.
[16]Liu H,Jia L,Chen X,et al.The Kv7/KCNQ channel blocker XE991 protects nigral dopaminergic neurons in the 6-hydroxydopamine rat model of Parkinson's disease[J].Brain Res Bull,2018,137:132-139.
[17]Bernardoseisdedos G,Nunez E,Gomisperez C,et al.Structural basis and energy landscape for the Ca2+gating and calmodulation of the Kv7.2K+channel[J].Proc Natl Acad Sci U SA,2018,115(10):2395-2400.
[18]Telezhkin V,Straccia M,Yarova P,et al.Kv7channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons[J].Pflugers Arch,2018,470(9):1-18.
[19]Bodor GS.Biochemical markers of myocardial damage[J].EJIF-CC,2016,27(2):95-111.
[20]Tzour A,Leibovich H,Barkai O,et al.KV7/M channels as targets for lipopolysaccharide‐induced inflammatory neuronal hyperexcitability[J].J Physiol,2016,595(3):713-718.