右美托咪定复合舒芬太尼对大鼠肺缺血再灌注损伤的作用探究

Effect of dexmedetomidine combined with sufentanil on pulmonary ischemia-reperfusion injury in rats

目的探讨右美托咪定复合舒芬太尼对大鼠肺缺血再灌注损伤(LIRI)的影响。方法将SD大鼠随机分为假手术组、模型组、舒芬太尼治疗组、右美托咪定治疗组和舒芬太尼+右美托咪定治疗组。除假手术组外,其余4组大鼠分别给予20μg/kg舒芬太尼、25.2μg/kg右美托咪定和20μg/kg舒芬太尼+25.2μg/kg右美托咪定,然后建立LIRI模型。试验结束后,通过HE染色、TUNEL染色观察肺组织结构,电镜观察肺细胞线粒体损伤,ELISA检测肺组织SOD、MDA水平,Western blot检测肺组织中LC3B、Beclin1、ATG5、HO-1和Nrf-2蛋白水平。结果20μg/kg舒芬太尼和25.2μg/kg右美托咪定及其联合使用均改善了LIRI大鼠肺组织损伤,降低了肺细胞凋亡,减轻了肺细胞线粒体肿胀,并降低了SOD、MDA表达,此外还降低了LC3B-Ⅱ、Beclin1、ATG5蛋白表达以及LC3B-Ⅱ/LC3B-Ⅰ比值,提高了LC3B-Ⅰ、Nrf-2、HO-1蛋白表达,其中20μg/kg舒芬太尼复合25.2μg/kg右美托咪定在3个治疗组中表现最好。结论右美托咪定、舒芬太尼及其联合使用均有效保护大鼠LIRI,右美托咪定与舒芬太尼对改善大鼠LIRI有协同作用,其机制可能与激活Nrf-2/HO-1抗氧化应激通路以及抑制过度自噬有关。

Objective To investigate the effects of dexmedetomidine combined with sufentanil on lung ischemia-reperfusion injury(LIRI)in rats.Methods SD rats were randomly divided into the sham operation group,model group,sufentanil group,dexmedetomidine group and sufentanil+dexmedetomidine group(n=6 mice per group),and rats in these groups were given 20μg/kg sufentanil,25.2μg/kg dexmedetomidine and 20μg/kg sufentanil+25.2μg/kg dexmedetomidine,respectively.The LIRI model was then established.The lung tissue structure was observed by HE staining and TUNEL staining,and the mitochondrial damage of lung cells was observed by electron microscopy.The levels of SOD and MDA in lung tissues were detected by ELISA,and the protein levels of LC3 B,Beclin1,ATG5,HO-1 and Nrf-2 in lung tissues were detected by Western blot.Results Sufentanil and dexmedetomidine alone or together improved lung tissue damage,reduced lung cell apoptosis,alleviated mitochondrial swelling of lung cells and decreased the expression of SOD and MDA in LIRI rats.The three treatments also decreased the protein expressions of LC3 B-Ⅱ,Beclin1 and ATG5 and the ratio of LC3 B-Ⅱ/LC3 B-Ⅰand increased the protein expressions of LC3 B-Ⅰ,Nrf-2 and HO-1 in LIRI rats.Among the three treatments,the combination of sufentanil and dexmedetomidine had the best performance.Conclusions Dexmedetomidine,sufentanil and the combination effectively improved LIRI in rats.Dexmedetomidine and sufentanil have a synergistic effect on improving LIRI in rats,and the mechanism might be related to the activation of the NRF-2/HO-1 antioxidant stress pathway and inhibition of excessive autophagy.