To investigate the changes of tyrosine kinase Src and tyrosine phosphatase SHP-2 and their significance in sepsis-associated encephalopathy.

Eighty-eight Wistar rats were randomly divided into septic group (n=80) and control group (n=60); intraperitoneal injection of 10 mg/kg of lipopolysaccharide (LPS) was given to induce sepsis-associated encephalopathy models in the septic group; and 10 mg/kg 0.9% normal saline was given to the rats in the control group. Animals were sacrificed and brain tissues were quickly removed at the indicated time points (0 h for control group and 6, 12, 24 and 48 h after injections for septic group). Western blotting, real time quantitative-PCR and immunofluorescence were used to analyze the protein and mRNA alterations of Src and SHP-2. Activities of mitochondrial oxidative phosphorylation complexes I-V were measured by enzyme assay kits, and enzyme activities with or without pretreatment of mitochondrial proteins with active Src or SHP-2 were analyzed.

Western blotting and real time-PCR indicated that Src levels in the septic group were obviously decreased at the 6 h and till the 48 h, with significant differences as compared with those in the control group (P<0.05); however, the opposite trend was noted in the SHP-2 levels. Immunofluorescence showed the same results of Western blotting. Pretreatment of mitochondrial proteins with active Src significantly enhanced complex I, II and III activities in vitro, while pretreatment of active SHP-2 produced opposite effects; significant difference was noted between the two (P<0.05).

Brain mitochondrial dysfunction of septic rat is partly affected due to a decrease in mitochondria proteins tyrosine phosphorylation by Src and SHP-2.

Sepsis-associated encephalopathy; Mitochondrial dysfunction; Tyrosine kinase; Tyrosine phosphatase