KUN XIE1, JINGUI YU2, GUOYONG SUN1, CHUANGANG LI1, HUI WANG3, XIAO LIU1, QING WEN3, SHUQIN WANG2
1Department of Anesthesiology, The Second Hospital of Shandong University, Jinan, Shandong, China - 2Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China - 3Blood Purification Center, The Second Hospital of Shandong University, Jinan, Shandong, China
Objective: To investigate the neuroprotective effect of mild hypothermia (MH) combined with n-Butylphthalide (NBP) on rats ischemia-reperfusion injury model. Methods Rats were divided into Sham group, MH group, Model group, NBP group and MH+NBP group. Rats in NBP and MH+NBP group were treated with NBT for 7 days before surgery, and solvent was used in other groups. Rat global cerebral ischemia-reperfusion model was constructed using Pulsinelli four-vessel occlusion method. Content of oxidative damage and inflammation related factors were measured using corresponding kit. Neuronal cell damage was detected by Nissl staining. Western blot was used to detect expression of Bcl-2, Bax, mTOR and NF-κB proteins.
Results: MDA, NO, NOS, IL-6 and IL-1β contents and levels of Bax, p-mTOR and p-NF-κB proteins were significantly increased and SOD content and expression level of Bcl-2 were significantly decreased in Model group compared with Sham group (p<0.05), while MH, NBP, and MH+NBP significantly inhibited those changes (p<0.05) and the inhibition effect of MH+NBP was the strongest. Numbers of neurons in MH, NBP, and MH+NBP were all increased compared with Model group, while this number was highest in MH+NBP group and showed no significant difference to that of Sham group.
Conclusion: MH+NBP played a better role in inhibiting oxidation damage and inflammatory response induced by cerebral ischemia-reperfusion than MH and NBP alone. The mechanism is possibly related to the inhibited phosphorylation of mTOR and NF-κB proteins, increase in expression level of anti-apoptotic proteins and decrease in expression level of pro-apoptotic proteins.
mild hypothermia, n-Butylphthalide, cerebral ischemia-reperfusion injury, neuroprotection, mTOR