TFAM Signaling Molecule Alleviates Mitochondrial damage of Cerebral Ischemia-Reperfusion

Objectives: In the present study, we aimed to investigate the antioxidant and therapeutic protective effects of mitochondrial transcription factor A (TFAM) signaling molecules on Mitochondrial damage of cerebral ischemia-reperfusion through. Methods: PC12 cells were stimulated with H ₂ O ₂ in vivo, and healthy SD rats were used to establish MCAO model in vitro. Longa neurological score was used to measure the behavior of SD rats. TTC staining was used to observe the ischemic infarction in the cerebral hemisphere of the lesion area. TEM was used to observe the morphological changes of mitochondria in nerve cells of brain tissue and PC12 cells. ROS/SDO/MDA/ATP detection kit was used to detect the corresponding indicators. RT-qPCR was used to detect the mRNA level of target gene and mtDNA copy number changes. Immunofluorescence and Western blot were used to detect the expression of target protein. Based on the Tfam gene study, we used lentivirus to down-regulate the Tfam gene by brain injection in vitro and by cell transfection in vitro. Results: After oxidative stress in the MCAO model of SD rats, the neurological score increased, the volume of ischemic area of cerebral infarction increased, the morphology of nerve cells in brain tissue and PC12 cells was disordered, the mitochondria appeared vacuolated, the contents of ROS and MDA increased, and the activity of SOD decreased. Oxidative stress causes mitochondrial dysfunction, resulting in the reduction of mtDNA copy number and the decreased expression of Tfam in brain tissue nerve cells and PC12 cells, which in turn affects mitochondrial transcription biogenesis and decreases the expression of Polrmt and Tfb ₂ M molecules. CAA promotes intracellular TFAM expression and activates its antioxidant pathway, thereby protecting mtDNA and alleviating oxidative stress and mitochondrial damage caused by MCAO in vitro and H ₂ O ₂ stimulation in vivo. Lentivirus down-regulates the expression of Tfam , and under its action, the antioxidant and mitochondrial protection effects of CAA are weakened. When Tfam was disrupted, the protective effect of CAA on mitochondria was inhibited. Conclusion: TFAM signaling molecules alleviates CIRI.