非诺贝特干预超氧化物歧化酶 2 转基因 C57BL/6J 小鼠的神经保护机制.

BACKGROUND: Oxidative injury is considered to be one of the important factors of cerebral ischemia-reperfusion injury. Superoxide dismutase 2 (SOD2) is a key mitochondrial antioxidant molecule, and fenofibrate can regulate the expression of SOD2 by activating peroxisome proliferator-activated receptor α.OBJECTIVE: To explore whether the mechanism of fenofibrate in the treatment of cerebral ischemia-reperfusion injury depends on the expression of SOD2. METHODS: The TALENs system was used to construct SOD2 transgenic mice. The transgenic mice were genotyped by PCR and DNA sequencing techniques. The expression of SOD2 protein in transgenic mice was detected by western blot assay. Wild-type and SOD2 transgenic mice were randomly divided into four groups: wild-type control group (n=6), wild-type fenofibrate group (n=6), SOD2 transgenic control group (n=5) and SOD2 transgenic fenofibrate group (n=5). A mouse model of middle cerebral artery occlusion was prepared using the suture-occlusion method. After 90 minutes of ischemia, the thread was removed to reperfuse cerebral blood flow for 30 minutes. A cerebral blood flow monitor was used to monitor local cerebral blood flow. Brain tissue slices were taken for 2,3,5-triphenyltetrazolium chloride staining to analyze the situation of cerebral infarction in each group. RESULTS AND CONCLUSION: After PCR and DNA sequencing analysis, nine SOD2+/+ transgenic mice were successfully constructed. After cerebral ischemiareperfusion, the wild-type fenofibrate group showed partial recovery of cerebral blood flow and significantly reduced cerebral infarction volume compared with the wild-type control group (P < 0.001). There was no significant difference in cerebral blood flow and cerebral infarction volume between the SOD2 transgenic fenofibrate group and the SOD2 transgenic control group. The SOD2 transgenic control was superior to the wild-type control group in terms of improving cerebral blood flow and cerebral infarction (P < 0.001). There were also no significant differences in cerebral blood flow and cerebral infarction volume between the wild-type fenofibrate group and the SOD2 transgenic control group and between the wild-type fenofibrate group and the SOD2 transgenic fenofibrate group. To conclude, the expression of SOD2 is one of the mechanisms of fenofibrate in the treatment of cerebral ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]