MedElevator
Войти в исследования Journal of inflammation (London, England) · 2025
In-depth investigation of the mechanism in rats with alcoholic acute pancreatitis via DNA methylation, intestinal flora, and fecal metabolomics.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Dong Haicheng, Ying Weixing, Zhu Shifeng
Аннотация
BACKGROUND: Alcohol consumption is the main cause of acute pancreatitis (AP). Alcohol combined with cerulein (CI) exerts direct damage to pancreas, with its mechanism undefined.
METHODS: Rats were randomly divided into three subgroups, with subgroup I including Control and Alcohol groups at weeks 6, 8, and 10, subgroup II including Control and Alcohol groups administered CI (12.5, 25, and 50 µg/kg), and subgroup III including Control and Alcohol groups administered CI (50 µg/kg). Following measurement of liver and kidney function indicators, pathological damage of liver, kidney, lung, and intestine was detected using HE staining. Methylation-Specific PCR, Sequenom MassARRAY methylation, ELISA, Western blot, and correlation analysis of 16S rRNA sequencing and metabolomics were performed.
RESULTS: Compared to Control group, Alcohol + CI group increased pathological damage, serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, blood urea nitrogen, alkaline phosphatase, amylase, lipase, TNF-α, IL-6, and IL-1β levels (P < 0.01). Meanwhile, p-mTOR/mTOR, hypoxia-inducible factor 1 alpha (HIF-1α), and vascular endothelial growth factor were enhanced, with lower creatinine and HIF-1α DNA methylation (P < 0.01). Alcohol at week 8 caused higher HIF-1α-25_CpG_35 methylation (P = 0.0222), which were reduced by further CI (50 µg/kg, P = 0.0034). Moreover, strong correlation was reported between key flora (Methanobrevibacter_A, Ruminococcus_C_59129, Lactobacillus, Eubacterium_Q, and Phascolarctobacterium_A) and metabolites (Homocysteine, Aspartic acid, Agmatine, 6-Ketoprostaglandin e1, Stearic acid, and Palmitic acid).
CONCLUSION: HIF-1α-25_CpG_35 methylation, intestinal flora, and metabolites involved in regulating AP pathogenesis. Methanobrevibacter_A, Ruminococcus_C_59129, Lactobacillus, Eubacterium_Q, Phascolarctobacterium_A, Homocysteine, Aspartic acid, Agmatine, 6-Ketoprostaglandin e1, Stearic acid, and Palmitic acid were the potential biomarkers, offering new insights into the pathogenesis of AP.
METHODS: Rats were randomly divided into three subgroups, with subgroup I including Control and Alcohol groups at weeks 6, 8, and 10, subgroup II including Control and Alcohol groups administered CI (12.5, 25, and 50 µg/kg), and subgroup III including Control and Alcohol groups administered CI (50 µg/kg). Following measurement of liver and kidney function indicators, pathological damage of liver, kidney, lung, and intestine was detected using HE staining. Methylation-Specific PCR, Sequenom MassARRAY methylation, ELISA, Western blot, and correlation analysis of 16S rRNA sequencing and metabolomics were performed.
RESULTS: Compared to Control group, Alcohol + CI group increased pathological damage, serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, blood urea nitrogen, alkaline phosphatase, amylase, lipase, TNF-α, IL-6, and IL-1β levels (P < 0.01). Meanwhile, p-mTOR/mTOR, hypoxia-inducible factor 1 alpha (HIF-1α), and vascular endothelial growth factor were enhanced, with lower creatinine and HIF-1α DNA methylation (P < 0.01). Alcohol at week 8 caused higher HIF-1α-25_CpG_35 methylation (P = 0.0222), which were reduced by further CI (50 µg/kg, P = 0.0034). Moreover, strong correlation was reported between key flora (Methanobrevibacter_A, Ruminococcus_C_59129, Lactobacillus, Eubacterium_Q, and Phascolarctobacterium_A) and metabolites (Homocysteine, Aspartic acid, Agmatine, 6-Ketoprostaglandin e1, Stearic acid, and Palmitic acid).
CONCLUSION: HIF-1α-25_CpG_35 methylation, intestinal flora, and metabolites involved in regulating AP pathogenesis. Methanobrevibacter_A, Ruminococcus_C_59129, Lactobacillus, Eubacterium_Q, Phascolarctobacterium_A, Homocysteine, Aspartic acid, Agmatine, 6-Ketoprostaglandin e1, Stearic acid, and Palmitic acid were the potential biomarkers, offering new insights into the pathogenesis of AP.