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Objective:To elucidate the effects of andrographolide (AG) against acute pancreatitis (AP)-associated kidney injury and explore the potential mechanism.Methods:Thirty-two C57BL/6 mice were divided into control group, AP group, AG treatment group and AG control group. In AP group, AP model was established by intraperitoneal injection of L-arginine and LPS. AG treatment group was intravenously injected with AG 8 h before the model establishment. The control group was intraperitoneally injected with an equal volume of normal saline. The AG control group was intravenously injected with AG 8 h before the intraperitoneal administration of normal saline. Venous blood of inner canthus in mice was collected, and the levels of amylase, creatinine (Scr) and urea nitrogen (BUN) in serum were detected. Pancreatic and double kidney tissues were also collected. Pancreatic myeloperoxidase (MPO) activity was detected by colorimetry. Histopathological changes of pancreas and kidneys were observed under light microscope and pathological score was evaluated. Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was used to analyze metabonomics in renal tissue.Results:Compared to the control group, the levels of amylase, Scr and BUN in serum and pancreatic MPO activity in the AP group were obviously increased [(13.78±6.01)U/L to (0.23±0.04)U/L, (79.81±24.03)μmol/L to (9.02±2.87)μmol/L, (34.76±14.53)mmol/L to (8.52±2.55)mmol/L, (16.55±4.23)U/g pro to (2.32±0.55)U/g pro]; histopathologic scores of pancreas and kidney in the AP group were also increased (2.70±0.26 to 0.20±0.12, 3.00±0.35 to 0.30±0.12), and the differences were statistically significant (all P<0.05). The levels of amylase, Scr and BUN in serum and pancreatic MPO activity in the AG treatment group were decreased than the AP group [(8.26±3.87)U/L to (13.78±6.01)U/L, (55.42±17.25)μmol/L to (79.81±24.03)μmol/L, (20.66±10.30)mmol/L to (34.76±14.53)mmol/L, (11.51±3.29)U/g pro to (16.55±4.23)U/g pro]; histopathologic scores of pancreas and kidney were also decreased in the AG treatment group than those in the AP group (1.40±0.19 to 2.70±0.26、1.70±0.26 to 3.00±0.35), and the differences were statistically significant (all P<0.05). Metabonomics analysis detected a total of 31 metabolites. Most of metabolites were involved in amino acid and fatty acid metabolism, and a few of them were also involved in glucose, nucleotide, vitamin and bile acid metabolism. Conclusions:AG exerts protective effects on AP-associated kidney injury by altering the levels of multiple metabolites.
RESUMO
Objective To investigate the potential mechanism of Rhizoma Coptidis extracts (RCE) against sepsis associated with acute kidney injury. Methods C57BL/6 mice were divided into sham group, model group and RCE treatment group. The levels of Scr and BUN were measured by test kits. Gas chromatography-mass spectrometry was used to analyze metabolic changes in kidneys. Results The levels of Scr and BUN were increased in the model group than sham, which were reversed by RCE. 16 metabolites related to the progress of sepsis associated with acute kidney injury were detected, which were involved in amino acid metabolism and carbohydrate metabolism. Among these metabolites, the level of 8 metabolites can be reversed with RCE treatment. Conclusion RCE might exert therapeutic effects in sepsis associated with acute kidney injury by altering multiple metabolic pathways.