Identical MicroRNAs Regulate Liver Protection during Anaesthetic and Ischemic Preconditioning in Rats: An animal study

<div><p>Anaesthetic preconditioning (APC) and ischemic preconditioning (IPC) ameliorate liver ischemia–reperfusion (I/R) injury and are important for regulating hepatic I/R injury. MicroRNAs (miRNAs) are short, noncoding RNA molecules of 21–23 nucleotides in length, and are currently under intensive investigation regarding their ability to regulate gene expression in a wide range of species. miRNA activity is involved in controlling a wide range of biological functions and processes. We evaluated whether APC and IPC are mediated by the same miRNAs by performing comprehensive miRNA screening experiments in a rat model of hepatic I/R injury. Twenty-one rats were randomly divided into three groups (n = 7/group): control (mock preconditioning), APC, and IPC. Control rats were subjected to 60 min of hepatic ischemia followed by 4 h of reperfusion, whereas the APC and IPC groups were preconditioned with 2% sevoflurane and hepatic ischemia for 10 min prior to ischemia-reperfusion, respectively. Liver samples were collected to measure miRNA levels after 3 h of reperfusion, and gene networks and canonical pathways were identified using Ingenuity Pathway Analysis (IPA). Blood samples were collected to measure the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Although haemodynamic parameters did not vary among the groups, AST and ALT levels were significantly higher in the control group than in the APC and IPC groups. Comprehensive miRNA screening experiments revealed that most miRNAs altered in the APC group were common to those in the IPC group. IPA identified five miRNAs related to the Akt–glycogen synthase kinase-3β (GSK-3β)–cyclin D1 pathway that were significantly affected by both preconditioning strategies. The application of either APC or IPC to ameliorate hepatic I/R injury results in expression of several common miRNAs that are related to the Akt–GSK–cyclin D1 pathway.</p></div

Functional network of down-regulated (green) microRNAs in the APC and IPC groups.

<p>All the miRs, except miR-17, repress Akt activation. miR-1, miR-17, and miR-133 suppress cyclin D expression. The image was created using the Ingenuity Pathway Analysis software. Solid lines represent direct interactions, and dashed lines represent indirect interactions.APC, anaesthetic preconditioning; IPC, ischemic preconditioning</p

Diagram of the experimental protocol.

<p>Black areas represent the periods of hepatic ischemia. All animals were subjected to 60 min of ischemia and 180 min of reperfusion. A minimal alveolar dose of sevoflurane was administered for 10 min followed by a 10 min washout period in the APC group.APC, anaesthetic preconditioning; IPC, ischemic preconditioning</p

Systemic haemodynamic parameters.

<p>Data are presented as means±SD.</p><p>APC, anaesthetic preconditioning; IPC, ischaemic preconditioning</p><p>Systemic haemodynamic parameters.</p