摘要
目的探讨右美托咪定(dexmedetomidine,Dex)减轻大鼠肾缺血再灌注的机制及致肝损伤中的作用研究。方法将60只雄性SD大鼠依据随机数字法分为3组:假手术组(Sham组)、肾缺血再灌注损伤(renal ischemia-reperfusion injury,RIRI)组和使用Dex预处理组,按照Dex剂量高低又分为低剂量组(12.5μg/kg),中剂量组(25μg/kg)和高剂量组(50μg/kg),每组12只。Sham组大鼠与RIRI组大鼠进行相同的手术,但不进行肾蒂封闭处理。RIRI组大鼠使用非创伤性血管钳封闭双肾蒂,导致其缺血,封闭45 min后开放肾蒂。Dex预处理各剂量组大鼠在手术前30 min分别腹腔注射12.5、25、50μg/kg的Dex。手术后取血离心,随后处死大鼠,并取出肝脏和肾脏,使用全自动生化仪检测各组大鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,Elisa法检测血清和肝组织中白细胞介素(IL)-6和8、和肿瘤坏死因子-α(TNF-α)水平,Western Blot法检测肾组织中HMGB1、TLR4和NF-κB蛋白表达水平。所有实验数据中,组间计量资料比较采用配对t检验或方差分析,计数资料比较采用χ^(2)检验,以P<0.05为差异有统计学意义。结果(1)与Sham组相比,RIRI组和Dex预处理各剂量组大鼠血清BUN、SCr及UA水平显著增高(P<0.01);(2)TNF-α、IL6、IL8在肝组织的表达水平,相较于Sham组,在RIRI组和Dex预处理剂量组中显著增高(P<0.01)。与RIRI组大鼠相比,Dex预处理组随着Dex剂量的增高IL-6、IL-8和TNF-α逐渐下降,其中低剂量组IL-6和TNF-α下降不明显,差异无统计学意义(P>0.01),而低剂量组的IL-8及中、高剂量组的明显下降,差异有统计学意义,IL-6、IL-8和TNF-α明显下降,差异具有统计学意义(P<0.01);与Sham组相比,RIRI组和Dex预处理各剂量组大鼠血清IL-6、IL-8和TNF-α水平显著调高(P<0.01),差异有统计学意义。与RIRI组大鼠相比,Dex预处理组随着Dex剂量的增高IL-6、IL-8和TNF-α逐渐下降,差异均具有统计学意义(P<0.01);(3)TLR-4,HMGB1,NF-κB在大鼠肾组织的表达水平,相较于Sham组,在RIRI组和Dex预处理组中明显升高(P<0.01),差异有统计学意义。与RIRI组相比,在Dex预处理组,TLR-4、HMGB1、NF-κB的表达水平随着Dex剂量的升高而逐渐降低,降低水平变化都有统计学意义(P<0.01)。结论右美托咪定可减轻大鼠肾缺血再灌注所致的肝损伤,其机制可能与HMGB1/TLR4/NF-κB信号通路有关。
Objective To investigate the mechanism of dexmedetomidine(Dex)in reducing renal ischemia and liver injury.Methods 60 male SD rats were divided into three groups according to random number method:Sham group,renal ischemia-reperfusion injury(RIRI)group and Dex pretreatment group.According to Dex dose,the rats were divided into low-dose group(12.5μg/kg),medium-dose group(25μg/kg)and high-dose group(50μg/kg),with 12 rats in each group.Rats in the Sham group underwent the same operation as rats in the RIRI group,but renal pedicle closure was not performed.In the RIRI group,non-invasive vascular forceps were used to block both renal pedicles,resulting in ischemia,and the renal pedicles were opened after 45 minutes of occlusion.Dex pretreatment:Rats in each dose group were intraperitoneally injected with 12.5,25 and 50μg/kg Dex 30 min before surgery.After surgery,blood was taken for centrifugation,then the rats were sacrificed,liver and kidney were taken out,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were detected by automatic biochemical analyzer,and interleukin(IL-6),interleukin(IL-8)and tumor necrosis factor-α(TNF-α)levels in serum and liver tissues were detected by Elisa.The expression levels of HMGB1,TLR4 and NF-κB protein in renal tissues were detected by Western Blot.In all experimental data,measurement data between groups were compared using paired t test or analysis of variance.χ2 test was used for comparison of count data,and there was statistically significant(P<0.05).Results(1)BUN,SCr and UA levels were significantly higher in RIRI and Dex pretreatment group compared with Sham group(P<0.01);(2)the expression levels of TNF-α,IL6 and IL8 in liver tissue were significantly increased in RIRI group and Dex pretreatment dose group compared with Sham group(P<0.01).Compared with the RIRI group,IL-6,IL-8 and TNF-αdecreased gradually in the Dex pretreatment group with the increase of Dex dose,while the IL-6 and TNF-αdecreased,not significantly in the low-dose group,and the difference was not statistically significant(P>0.01),while the IL-8 decreased significantly in the low-dose group,medium and high-dose groups,and the difference was statistically significant.Il-6,IL-8 and TNF-αdecreased significantly,with statistical significance(P<0.01);compared with Sham group,serum LEVELS of IL-6,IL-8 and TNF-αin RIRI group and Dex pretreatment groups were significantly increased(P<0.01),and the differences were statistically significant.Compared with RIRI group,IL-6,IL-8 and TNF-αin Dex pretreatment group decreased gradually with the increase of Dex dose,with statistically significant differences(P<0.01);(3)the expression levels of TLR-4,HMGB1 and NF-κB in renal tissues of rats were significantly increased in the RIRI group and the Dex pretreatment group compared with the Sham group(P<0.01),and the differences were statistically significant.Compared with RIRI group,the expression levels of TLR-4,HMGB1 and NF-κB in Dex pretreatment group decreased gradually with the increase of Dex dose,and the changes of the decreased levels were significant(P<0.01).Conclusion Dexmedetomidine can reduce hepatic injury induced by renal ischemia-reperfusion in rats,and the mechanism may be related to HMGB1/TLR4/NF-κB signaling pathway.
作者
鹿文琪
李小绪
Lu Wenqi;Li Xiaoxu(Department of Anesthesiology,the First Affiliated Hospital of Bengbu Medical College;Department of Neurosurgery,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233000 China)
出处
《锦州医科大学学报》
2022年第3期18-23,共6页
Journal of Jinzhou Medical University
