RESUMEN
Objective: To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs. Methods: An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-â t test was used for pairwise comparison. Results: ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2(+/+)), heterozygous mutant (ALDH2(+/-)), and homozygous mutant (ALDH2(-/-)), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group (Pâ <â 0.05), while the ALT, AST,ALP, and TBil were all elevated in the APAP experimental group. The levels of ALT (Pâ â =â 0.004), AST (Pâ =â 0.002), and TBil (Pâ =â 0.012) were significantly elevated among the mutant group compared to those in the wild-type group, and the expression levels of these indicators were also significantly elevated among the homozygous mutant group compared to those in the heterozygous mutant group (Pâ =â 0.003, 0â and 0.006). In addition, the ALP levels were higher in the heterozygous mutation group than those in the homozygous mutant group (Pâ =â 0.085) and wild-type group mice, but the difference was only statistically significant compared to wild-type mice (Pâ =â 0.002). HE staining results showed that mice in the APAP experimental group had hepatocyte degeneration, necrosis, and increased inflammatory cell infiltration, which was mostly evident in mutant mice. Simultaneously, the F4/80 immunohistochemical staining results showed that brown granules were visible in the liver tissue of APAP experimental group mice, and its expression levels were significantly enhanced compared to the blank control group. Conclusion: APAP-induced liver function abnormalities were associated with the ALDH2 gene polymorphism. The liver injury symptoms were increased in ALDH2 mutant mice following APAP modeling, and the ALDH2 gene defect may alleviate, to some extent, APAP-induced liver function abnormalities.
Asunto(s)
Aldehído Oxidorreductasas , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Ratones , Acetaminofén/efectos adversos , Acetaminofén/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/patología , Hígado/patología , Ratones Noqueados , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Alanina TransaminasaRESUMEN
As an important medical support component for the army to preserve and enhance combat effectiveness and minimize the reduction rate of combat personnel, war trauma treatment has been highly valued. Modern war puts forward higher requirements for the pertinence, practicality, and efficiency of war trauma treatment training. With the comprehensive development of national defense and military modernization, the contradiction between the increasing demand of modern war medical service and the relatively backward training mode of war trauma treatment becomes more and more prominent. As a new practical technology, virtual reality technology can simulate the elements of war trauma treatment in a panoramic manner, enabling the trainees to have a real sense of the battlefield in the four-dimensional space of high simulation, which has unique advantage in the field of war trauma treatment training. At present, the western developed countries represented by the the United States of America have applied virtual reality technology in the field of war trauma treatment training and achieved gratifying training results through the actual combat tests. This paper reviews the application of virtual reality technology in the field of war trauma treatment training at home and abroad, in order to provide a new idea and method for improving the level of war trauma treatment training in our army.