糖尿病因素削弱右美托咪定对肾缺血再灌注后心肌损伤的保护作用

Diabetic factors impair the protective effect of dexmedetomidine on myocardial injury after renal ischemia-reperfusion

目的 探讨糖尿病因素削弱右美托咪定对肾缺血再灌注后心肌损伤的保护作用的机制。方法 30只Wistar大鼠在构建2型糖尿病模型期间有6只大鼠死亡,24只大鼠建模成功,随机分为模型+盐水组(DM-C组)、模型+肾缺血再灌注组(DM-IR组)和模型+右美托咪定预处理组(DM-DP组)。另取24只非2型糖尿病大鼠作为对照并随机分为正常+盐水组(NDM-C组)、正常+肾缺血再灌注组(NDM-IR组)和正常+右美托咪定预处理组(NDM-DP组)。模型+盐水组和正常+盐水组大鼠只开腹;肾缺血再灌注处理:建立肾缺血再灌注(RIR)模型;右美托咪定预处理:肾缺血再灌注组基础上以2μg·kg-1·h-1的速率于缺血前30 min起泵注至再灌注后4 h泵注右美托咪定。实验结束时留取心肌组织和血清标本。采用Western blot法测定心肌组织核因子-κB(NF-κB p65)和p-NF-κB p65,采用ELISA法测定血清肌钙蛋白I(cTnI)、白介素-17a(IL-17a)、白介素-10(IL-10)水平,采用TUNEL染色测定心肌凋亡率。结果 与NDM-C组比较,NDM-IR组cTnI、IL-17a、凋亡率升高,NF-κB p65表达增高,IL-10水平降低(P<0.05),p-NF-κB p65差异无统计学意义(P>0.05);与NDM-IR组比较,NDM-DP组IL-17a、NF-κB p65表达降低、IL-10水平升高(P<0.05),p-NF-κB p65差异无统计学意义(P>0.05);与DM-C组比较,DM-IR组和DM-DP组cTnI、IL-17a、p-NF-κB p65、凋亡率升高,IL-10降低(P<0.05);与DM-IR组比较,DM-DP组cTnI、IL-17a、p-NF-κB p65、凋亡率降低,IL-10升高(P<0.05);与NDM-DP组比较,DM-DP组cTnI、IL-17a、凋亡率、NF-κB p65、p-NF-κB p65升高,IL-10降低(P<0.05)。结论 炎症机制参与了糖尿病因素削弱右美托咪定预处理对RIR后心肌保护作用。

Objective To investigate the mechanism of diabetes impairing the protective effect of dexmedetomidine on myocardial injury after renal ischemia-reperfusion.Methods During the construction of a type 2 diabetes model,6 out of 30 Wistar rats died,and 24 rats were successfully modeled.They were randomly divided into a model+saline group(DM-C group),a model+renal ischemia-reperfusion group(DM-IR group),and a model+dexmedetomidine pretreatment group(DM-DP group).Another 24 non type 2 diabetic rats were selected as controls and randomly divided into a normal+saline group(NDM-C group),a normal+renal ischemia-reperfusion group(NDM-IR group),and a normal+dexmedetomidine pretreatment group(NDM-DP group).The model+saline group and the normal+saline group were only open the abdomen without operation.Renal ischemia reperfusion treatment:RIR model was established.Dexmedetomidine preconditioning treatment:Dexmedetomidine was pumped at a rate of 2μg·kg-1·h-130 minutes before left renal ischemia to 4 hours after reperfusion on the basis of renal ischemia reperfusion group.At the end of the experiment,myocardial tissue and serum samples were taken.The expression of NF-κB p65 and p-NF-κB p65 in myocardial tissue was measured by Western blot.The levels of serum cTnI,IL-17a and IL-10 were measured by ELISA.The apoptosis rate of myocardial cells were determined by TUNEL staining.Results Compared with NDM-C group,in NDM-IR group,cTnI,IL-17a,apoptosis rate was increased,NF-κB p65 expression was increased,IL-10 level was decreased(P<0.05),p-NF-κB p65 expression had no significant difference(P>0.05).Compared with NDM-IR group,the expression of IL-17a and NF-κB p65 in NDM-DP group was decreased,and the level of IL-10 was increased(P<0.05),p-NF-κB p65 expression had no significant difference(P>0.05).Compared with DM-C group,cTnI,IL-17a,p-NF-κB p65 and apoptosis rate in DM-IR group and DM-DP group was increased,while IL-10 was decreased(P<0.05).Compared with DM-IR group,the expression of cTnI,IL-17a,p-NF-κB p65 and apoptosis rate in DM-DP group was decreased,and IL-10 was increased(P<0.05).Compared with NDM-DP group,the expression of cTnI,IL-17a,apoptosis rate,NF-κB p65,p-NF-κB p65 in DM-DP group was increased,and IL-10 was decreased(P<0.05).Conclusion Inflammatory mechanism is involved in diabetes,which weakens the protective effect of dexmedetomidine pretreatment on myocardium after RIR.