Role of microRNA-133a-5p and its mechanism of action in prevention and treatment of hepatic ischemia-reperfusion injury in rats with propofol
Objective To observe the role of microRNA-133a-5p(miR-133a-5p)in the prevention and treatment of hepatic ischemia/reperfusion(I/R)injury in rats with propofol and to investigate its mechanism.Methods ① Effects of propofol on liver function and mRNA expression of miR-133a-5p and mitogen-activated protein kinase 6(MAPK6)in I/R rats:18 rats were divided into the propofol group,model group,and control group,with 6 rats in each group.Rats in the propofol group and the model group were subjected to I/R of liver tissues,and meanwhile,rats in the propofol group were injected with 0.6 mg/(kg·min)propofol.At the end of reperfusion,4 mL of blood was collected from the inferior vena ca-va of rats in each group,and the serum liver function indexes of aspartate aminotransferase(AST)and alanine aminotrans-ferase(ALT)were detected using an automatic biochemical analyzer.Liver tissues were separated from rats in each group by executing the rats after the collection of blood,and miR-133a-5p,and MAPK6 mRNAs of the liver tissues of the rats were detected using qRT-PCR.② Effects of miR-133a-5p inhibitor combined with propofol on liver function and expres-sion of miR-133a-5p and MAPK6 mRNA in liver tissues of I/R rats:another 24 rats were taken and divided into groups A,B,C,and D,with 6 rats in each group.Rats in all four groups were subjected to I/R operation on liver tissues,rats in the group A were injected with 0.6 mg/(kg·min)propofol and miR-133a-5p inhibitor at the same time during the I/R opera-tion,and meanwhile,rats in the groups B and C were injected with 0.6 mg/(kg·min)propofol,and equal volume of nor-mal saline,and rats in the group D did not receive any treatment.At the end of reperfusion,4 mL of blood was collected from the inferior vena cava of rats in each group,and serum ALT and AST were detected using an automatic biochemical analyzer.Liver tissues were separated from rats in each group by executing them after blood collection,and miR-133a-5p and MAPK6 mRNA were detected in liver tissues of the four groups by qRT-PCR.Results Compared with the control group,rats in the model group had increased serum AST and ALT activity,decreased relative expression of miR-133a-5p and increased relative expression of MAPK6 mRNA in the liver tissues(all P<0.01);compared with the model group,rats in the propofol group had decreased serum AST and ALT levels and increased expression of miR-133a-5p in the liver tissues,and decreased MAPK6 mRNA expression(all P<0.05).Compared with group B,rats in group A had higher se-rum ALT and AST levels and higher relative expression of MAPK6 mRNA in the liver tissues(all P<0.01);compared with groups B and C,rats in the group D had increased serum ALT and AST levels and higher relative expression of MAPK6 mRNA in the liver tissues(all P<0.01).Conclusions The degree of liver injury is reduced in hepatic I/R rats after pro-pofol injection,and miR-133a-5p expression increases and MAPK6 mRNA expression decreases in the liver tissues.Inhi-bition of miR-133a-5p expression reverses the preventive effect of propofol on hepatic I/R injury in rats.Propofol may at-tenuate hepatic I/R injury in rats by promoting miR-133a-5p expression and inhibiting MAPK6 mRNA expression in the liver tissues.
propofolischemia-reperfusionischemia-reperfusion injuryaspartate aminotransferasealanine ami-notransferase microRNAmicroRNA-133a-5pmitogen-activated protein kinase 6