Wang Chaoyu, Huang Yaqian, Gong Yating, Wu Muyao, Jiang Lei, Dang Baoqi
Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
These authors contributed eqully to this work.
Iran J Basic Med Sci. 2024;27(3):352-359. doi: 10.22038/IJBMS.2023.72947.15862.
Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage and mutation is widely accepted as one of the pathological processes of neurodegenerative diseases. As an mtDNA binding protein, mitochondrial transcription factor A (TFAM) maintains the integrity of mtDNA through transcription, replication, nucleoid formation, damage perception, and DNA repair. In recent works, the overexpression of TFAM increased the mtDNA copy count, promoted mitochondrial function, and improved the neurological dysfunction of neurodegenerative diseases. The role of TFAM in neurodegenerative diseases has been well explained. However, the role of TFAM after surgical brain injury (SBI) has not been studied. In this work, we aimed to study the role of TFAM in the brain after SBI and its mechanism of action.
One hour after the occurrence of SBI, tetramethylpyrazine (TMP) was injected into the abdominal cavity of rats, and the brain was collected 48 hr later for testing. The evaluation included neurobehavioral function test, brain water content measurement, immunofluorescence, western blot, TUNEL staining, FJC staining, ROS test, and ATP test.
After SBI, the content of TFAM on the ipsilateral side increased and reached a peak at about 48 hr. After intraperitoneal injection of TMP in rats, 48 hr after SBI, the concentration of TFAM, Bcl-2, and adenosine triphosphate (ATP) increased; the content of caspase-3, reactive oxygen species (ROS), and cerebral edema decreased; and the nerve function significantly improved.
TMP inhibited cell apoptosis after SBI in rats by up-regulating TFAM and protecting brain tissues.
线粒体DNA（mtDNA）损伤和突变导致的线粒体功能障碍被广泛认为是神经退行性疾病的病理过程之一。作为一种mtDNA结合蛋白，线粒体转录因子A（TFAM）通过转录、复制、类核形成、损伤感知和DNA修复来维持mtDNA的完整性。在最近的研究中，TFAM的过表达增加了mtDNA拷贝数，促进了线粒体功能，并改善了神经退行性疾病的神经功能障碍。TFAM在神经退行性疾病中的作用已得到很好的解释。然而，TFAM在脑外科损伤（SBI）后的作用尚未得到研究。在这项研究中，我们旨在研究TFAM在SBI后脑内的作用及其作用机制。
SBI发生1小时后，将川芎嗪（TMP）注入大鼠腹腔，48小时后取脑进行检测。评估包括神经行为功能测试、脑含水量测量、免疫荧光、蛋白质免疫印迹法、TUNEL染色、FJC染色、活性氧测试和ATP测试。
SBI后，同侧TFAM含量增加，约48小时达到峰值。大鼠SBI后48小时腹腔注射TMP后，TFAM、Bcl-2和三磷酸腺苷（ATP）浓度升高；半胱天冬酶-3、活性氧（ROS）含量和脑水肿减轻；神经功能明显改善。
TMP通过上调TFAM保护脑组织，抑制大鼠SBI后的细胞凋亡。
