The efficacy and mechanism of Jiawei Xuanfu Daizhe decoction in treating esophageal precancerous lesions
SONG Xing-jian,ZHANG Ze,YOU Xu-ying
Abstract:
Objective To investigate the mechanism by which the Jiawei Xuanfu Daizhe decoction (JXDD) inhibits the progression of esophageal precancerous lesions by regulating mitochondrial oxidative phosphorylation function via the TFAM-mtDNA signaling pathway. Methods 100 male SD rats were randomly divided into a normal group, a model group, a western medicine group, a low-dose JXDD group, and a high-dose JXDD group. Except for the normal group, the other groups were used to establish an esophageal precancerous lesion model and were treated with corresponding drugs for 8 weeks. After the last administration, tissue samples were collected. Hematoxylin-eosin (HE) staining was used to observe the pathology of esophageal tissue; Western blot was used to detect the expression of mitochondrial DNA (mtDNA)-encoded proteins COX1 and COX2, as well as mitochondrial transcription factor A (TFAM) in the tissue; enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of TFAM in the cytosolic fraction of the tissue; and quantitative polymerase chain reaction (qPCR) was used to measure the mtDNA copy number. Finally, a cell model was constructed, and Western blot was used to detect the expression of HSP70 and TFAM in the cytosolic and mitochondrial fractions, while qPCR was used to measure the mtDNA copy number for verification. Results Compared with the model group, JXDD treatment alleviated hyperplasia of the esophageal mucosa and inflammatory cell infiltration, and reduced the pathological score (P <0.05). Western blot, ELISA, and qPCR results showed that in the JXDD group, TFAM expression in the mitochondria of esophageal tissue increased (P <0.05), while its expression in the cytosol decreased (P <0.05). The mtDNA copy number and the expression of mtDNA-encoded proteins COX1 and COX2 were also increased (P <0.05). An esophageal precancerous lesion cell model was successfully established, and Western blot and qPCR validated the above findings. Conclusion JXDD inhibits the development of esophageal precancerous lesions by promoting TFAM accumulation in mitochondria, increasing mtDNA copy number and expression, protecting the integrity of the electron transport chain, and ultimately enhancing mitochondrial oxidative phosphorylation function.
