不同剂量右美托咪定预处理对大鼠局灶性脑缺血再灌注损伤的影响
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摘要
目的:观察不同剂量右美托咪定(dexmedetomidine,DEX)预处理对大鼠局灶性脑缺血再灌注损伤的影响。方法:50只健康雄性SD大鼠,随机分为假手术组(Sham组)、缺血再灌注组(I/R组)、小剂量右美托咪定组(D1组)、中等剂量右美托咪定组(D2组)、较大剂量右美托咪定组(D3组)。Sham组仅行外科操作而不造成缺血,Sham组、I/R组于外科操作前30 min腹腔注射生理盐水1 m L,D1、D2、D3组分别于缺血操作前30 min腹腔注射DEX 50、100、200μg/kg。各组分别于术后24、48 h检测S100β蛋白含量,术后48 h测定Bcl-2、Bax含量及脑梗死体积比。结果:与Sham组相比,D1、D2、D3组S100β、Bax蛋白含量及脑梗死体积比均升高(P<0.05),Bcl-2含量降低(P<0.05);与I/R组相比,D1、D2、D3组S100β、Bax蛋白含量及脑梗死体积比均降低(P<0.05),Bcl-2含量升高(P<0.05);D1、D2、D3组间相比,D3组Bcl-2含量较D1、D2组降低(P<0.05),术后24 h S100β蛋白含量较D1、D2组升高(P<0.05),D1、D2组间差异无统计学意义;D1、D2、D3组间术后48 h S100β、Bax蛋白含量及脑梗死体积比差异无统计学意义。结论:右美托咪定预处理对局灶性脑缺血再灌注损伤大鼠有神经保护作用,其机制可能与抑制细胞凋亡有关,此作用在50和100μg/kg间无明显差异。
Objective:To explore the effects of different doses of dexmedetomidine(DEX)preconditioning on focal in cerebral ischemia reperfusion injury rats. Methods:Fifty healthy male Sprague-Dawley rats were randomly divided into the sham operation group(sham group),the ischemia-reperfusion group(I/R group),the low-dose dexmedetomidine group(D1 group),the medium-dose dexmedetomidine group(D2 group),and the larger-dose dexmedetomidine group(D3 group). The sham group received surgical procedures without causing ischemia. The sham group and the I/R group received 1 m L normal saline intraperitoneally 30 minutes before ischemia,and the D1,D2 and D3 groups were injected with dexmedetomidine in 50 μg/kg,100 μg/kg and 200 μg/kg,respectively. The levels of S100β protein were measured 24 h and 48 h after reperfusion,the contents of Bcl-2,Bax and the volume of cerebral infarction were determined 48 h after reperfusion. Results:Compared with the I/R group,the protein contents of S100β,Bax,and the volume of cerebral infarction in the D1,D2 and D3 groups were lower(P<0.05),but were higher than those in the sham group(P<0.05);the Bcl-2 expression were increased(P<0.05),but were lower than that in the sham group(P<0.05). The content of Bcl-2 was lower and the content of S100β protein at 24 h after surgery was higher in the D3 group than that in the D1 and D2 groups(P<0.05),but were not statistically different between the D1 and D2 groups. The expression level of protein S100β,Bax and the volume of cerebral infarction were not statistically different between the D1,D2 and D3 groups. Conclusion:Dexmedetomidine preconditioning has neuroprotective effect on focal cerebral ischemia reperfusion injury in rats,and the mechanism may be related to the inhibition of apoptosis. The effect of dexmedetomidine has no significant difference between 50 μg/kg and 100 μg/kg.
Objective:To explore the effects of different doses of dexmedetomidine(DEX)preconditioning on focal in cerebral ischemia reperfusion injury rats. Methods:Fifty healthy male Sprague-Dawley rats were randomly divided into the sham operation group(sham group),the ischemia-reperfusion group(I/R group),the low-dose dexmedetomidine group(D1 group),the medium-dose dexmedetomidine group(D2 group),and the larger-dose dexmedetomidine group(D3 group). The sham group received surgical procedures without causing ischemia. The sham group and the I/R group received 1 m L normal saline intraperitoneally 30 minutes before ischemia,and the D1,D2 and D3 groups were injected with dexmedetomidine in 50 μg/kg,100 μg/kg and 200 μg/kg,respectively. The levels of S100β protein were measured 24 h and 48 h after reperfusion,the contents of Bcl-2,Bax and the volume of cerebral infarction were determined 48 h after reperfusion. Results:Compared with the I/R group,the protein contents of S100β,Bax,and the volume of cerebral infarction in the D1,D2 and D3 groups were lower(P<0.05),but were higher than those in the sham group(P<0.05);the Bcl-2 expression were increased(P<0.05),but were lower than that in the sham group(P<0.05). The content of Bcl-2 was lower and the content of S100β protein at 24 h after surgery was higher in the D3 group than that in the D1 and D2 groups(P<0.05),but were not statistically different between the D1 and D2 groups. The expression level of protein S100β,Bax and the volume of cerebral infarction were not statistically different between the D1,D2 and D3 groups. Conclusion:Dexmedetomidine preconditioning has neuroprotective effect on focal cerebral ischemia reperfusion injury in rats,and the mechanism may be related to the inhibition of apoptosis. The effect of dexmedetomidine has no significant difference between 50 μg/kg and 100 μg/kg.
引文
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[10]郭淑娟,王琮民.性别因素对局灶脑缺血再灌注损伤大鼠脑梗死体积及脑血流的影响[J].山东医药,2016,56(4):29-31
[11]Wang Y,Han R.Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signalregulated kinase in rats with subarachnoid haemorrhage[J].Br J Anaesth,2016,116(3):384-392
[12]Miller DL,Dou C,Dong Z.The influence of dexmedetomidine on ultrasound-induced pulmonary capillary hemorrhage in rats[J].Ultrasound Med Biol,2016,42(4):964-970
[13]Liu G,Song H,Qiu L,et al.Dexmedetomidine preconditioning inhibits the long term inflammation induced by renal ischemia/reperfusion injury in rats[J].Acta Cir Bras,2016,31(1):8-14
[14]Jiang D,Wang Y,Zang Y,et al.Neuroprotective effects of rh GLP-1 in diabetic rats with cerebral ischemia/reperfusion injury[J].Drug Dev Res,2016,77(3):124-133
[15]Yan X,Cheng X,Zhou L,et al.Dexmedetomidine alleviates lipopolysaccharide-induced lung injury in Wistar rats[J].Oncotarget,2017,8(27):44410-44417
[2]Xiang YC,Xiao YG,Qin G,et al.Effects of dexmedetomidine postconditioning on myocardial ischemia and the role of the PI3K/Akt-dependent signaling pathway in reperfusion injury[J].Mol Med Rep,2016,14(1):797-803
[3]Li T,Qin JJ,Yang X,et al.The ubiquitin E3 ligase TRAF6 exacerbates ischemic stroke by ubiquitinating and activating Rac1[J].J Neurosci,2017,37(50):12123-12140
[4]Akp?nar H,Naz?rogˇlu M,?vey I·S,et al.The neuroprotective action of dexmedetomidine on apoptosis,calcium entry and oxidative stress in cerebral ischemia-induced rats:Contribution of TRPM2 and TRPV1 channels[J].Sci Rep,2016,6:37196
[5]Liu JR,Yuki K,Baek C,et al.Dexmedetomidine-induced neuroapoptosis is dependent on its cumulative dose[J].Anesth Analg,2016,123(4):1008-1017
[6]郑羡河,胡双燕,张昌锋,等.右美托咪啶对重度颅脑损伤患者术后颅内压的影响[J].中华麻醉学杂志,2012,32(2):148-151
[7]马燕,于湘友.不同剂量右美托咪定对脓毒症大鼠早期免疫调节的影响[J].中华急诊医学杂志,2016,25(9):1149-1153
[8]Ma XD,Hang LH,Shao DH,et al.TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats[J].Exp Neurol,2017,293:115-123
[9]Liu S,Zhu S,Zou Y,et al.Knockdown of IL-1βimproves hypoxia-ischemia brain associated with IL-6 up-regulation in cell and animal models[J].Mol Neurobiol,2015,51(2):743-752
[10]郭淑娟,王琮民.性别因素对局灶脑缺血再灌注损伤大鼠脑梗死体积及脑血流的影响[J].山东医药,2016,56(4):29-31
[11]Wang Y,Han R.Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signalregulated kinase in rats with subarachnoid haemorrhage[J].Br J Anaesth,2016,116(3):384-392
[12]Miller DL,Dou C,Dong Z.The influence of dexmedetomidine on ultrasound-induced pulmonary capillary hemorrhage in rats[J].Ultrasound Med Biol,2016,42(4):964-970
[13]Liu G,Song H,Qiu L,et al.Dexmedetomidine preconditioning inhibits the long term inflammation induced by renal ischemia/reperfusion injury in rats[J].Acta Cir Bras,2016,31(1):8-14
[14]Jiang D,Wang Y,Zang Y,et al.Neuroprotective effects of rh GLP-1 in diabetic rats with cerebral ischemia/reperfusion injury[J].Drug Dev Res,2016,77(3):124-133
[15]Yan X,Cheng X,Zhou L,et al.Dexmedetomidine alleviates lipopolysaccharide-induced lung injury in Wistar rats[J].Oncotarget,2017,8(27):44410-44417