Molecular mechanism of propofol reducing hepatic ischemia reperfusion cell apoptosis via miR-378
NIU Zhengrong
YANG Fei
SU Tao
JI Xiang
LI Xuebin
XU Guiping
Abstract：Objective To investigate the mechanism of propofol induced miR-378 reduce apoptosis and then prevent liver from ischemia reperfusion injury. Methods Forty five healthy adult SD rats were randomly divided into 3 groups:sham group, IR group and IR group treated with propofol and then surgically treated. The ischemia reperfusion injury of the liver was performed 60 minutes for ischemia and 120 minutes for reperfusion. Serum levels of alanine aminotransferase ( ALT) , as-partate aminotransferase ( AST) and lactate dehydrogenase ( LDH) were measured by automated biochemical analyzer to assess the degree of ischemia reperfusion injury. TUNEL assay was used to detect the apoptosis of liver tissue in three groups of rats. Western blot and QPCR were used to detect the expression of miR-378 and apoptosis related genes. Synthetic miR-378 mim-ics,site directed mutagenesis and dual luciferase reporter system were used to identify the target genes associated with apopto-sis downstream of miR 378. Results The levels of ALT, AST and LDH in IR group were significantly increased compared with sham group(t=17. 236, t=16. 527, t=14. 349,P<0. 01),whereas levels of ALT,AST and LDH in IR + propofol group were significantly lower than those in IR group(t=15. 626, t=14. 995, t=11. 376,P<0. 01). Compared with the sham group,the expressions of miR 378,Bcl-2 and Bcl-xl decreased in IR group(t=6. 921, t=11. 381, t=11. 467, P<0. 01). whereas the expression of Cytochrome c, Bax, Bak, caspase 9 and caspase 3 increased(t=14. 486, t=12. 653, t=11. 434, t=15. 712, t=15. 934,P=0. 000, P= <0. 01). Propofol treated IR reversed this expression pattern of IR group, made it more consistent with the sham group. TUNEL assay showed that the apoptotic rate in IR group was higher than sham group( t=22. 546,P=0. 000), and the apoptosis rate in propofol group decreased significantly(t=9. 765, P=0. 000). In human nor-mal hepatocytes QSG 7701 transfected with miR-378 mimics, the expression of Bcl-2 and Bcl-xl was significantly increased (t=15. 589, t=15. 715,P<0. 01),while the expressions of Cytochrome c,Bax, Bak, caspase 9 and caspase 3 were signifi-cantly decreased(t=12. 574, t=15. 607, t=14. 894, t=18. 828, t=11. 367,P<0. 01). Bak and caspase 3 were identified to be downstream targets of miR-378 via Site directed mutagenesis and dual luciferase reporter system. Conclusion Propofol can protect liver against ischemia reperfusion injury by inducing the expression of miR-378 and mediating apoptotic signals. Therefore,miR-378 may be a new target for the treatment of hepatic ischemia reperfusion injury.
Keywords：LiverIschemia reperfusion injuryApoptoticmiR378PropofolMolecular mechanismRats
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 614-620 )