Butyrate Ameliorates Intestinal Epithelial Barrier Injury Via Enhancing Foxp3+ Regulatory T-Cell Function in Severe Acute Pancreatitis Model.

BACKGROUND: This study aimed to examine the effect of sodium butyrate on severe acute pancreatitis-related gut barrier injury in a rat model and explore its mechanism. METHODS: Male rats randomly fell into 3 groups, that is, the control, the severe acute pancreatitis group, and the severe acute pancreatitis+butyrate group. Rats in the control group received sham operation, while rats in the severe acute pancreatitis group and severe acute pancreatitis+butyrate group received severe acute pancreatitis induction by intraductal infusion of 4% sodium taurocholate. After that, rats in the severe acute pancreatitis+butyrate group were fed with sodium butyrate solution with free access. Intestinal barrier injury was measured based on the expression of tight junction proteins by reverse transcription polymerase chain reaction, Western blotting assay as well as immunohistochemical staining. The variation of Treg cells was measured by reverse transcription polymerase chain reaction, Western blotting assay, immunohistochemical staining, and flow cytometry analysis. RESULTS: Compared to rats in the control, rats in the severe acute pancreatitis group showed significantly higher pathohistological scores (P < .001) in the intestine, as well as decreased expression of occludin and ZO-1. While, rats in the severe acute pancreatitis+butyrate group showed mitigated histologic lesions (P < .05) and increased expressions of occludin and ZO-1. In addition, rats in the severe acute pancreatitis group showed the obvious reduction in the expressions of Foxp3 and GPR109a and the decreased percentage of Treg cells in the intestine (P < .001) compared to rats in the control. However, rats in the severe acute pancreatitis+butyrate group showed markedly increased expressions of Foxp3 and GPR109a and the upregulated percentage of Treg cells (P < .01). CONCLUSION: Butyrate could significantly mitigate the intestinal injury induced by severe acute pancreatitis, probably by inducing the differentiation of Treg cells.

Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery.

BACKGROUND: About 30-50% patients develop acute kidney injury (AKI) after cardiac surgery, which is still diagnosed by serum creatinine on clinic. However, the increase of serum creatinine is insensitive and delayed. The aim of this study is to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are early biomarkers for AKI in patients after cardiac surgery. METHODS: Thirty-three cases undergoing cardiac surgery were classified into an AKI group and non-AKI group, according to the AKI definition (> 26.5 micromol/L increase of serum creatinine, more than or equal to 50% increase of serum creatinine within 48 h, or a reduction in urine output < 0.5 mL/Kg per hour for more than six hours). The concentrations of serum NGAL, urine NGAL, and urine IL-18 at different time-points were measured. RESULTS: Nine cases (27.27%) developed postoperative AKI, but diagnosis with serum creatinine was 12-48 h postoperation. The concentrations of serum NGAL were not significantly increased postoperation. The concentrations of urine NGAL and IL-18 were significantly increased in the AKI group, which reached the peak at 2-4 h postoperation, and a more significant difference could be seen after correction for urine creatinine. The concentrations of urine NGAL and IL-18 2 h postoperation, either corrected for urine creatinine or not, showed good sensitivity and specificity. Increased levels of urine NGAL and IL-18 2 h postoperation were significantly correlated with increased level of serum creatinine 12 h postoperation. Logistic regression analysis showed that urine NGAL corrected for urine creatinine 2 h postoperation and urine IL-18 2 h postoperation emerged as powerful independent predictors of AKI after cardiac surgery. CONCLUSIONS: The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery, especially after correction for urine creatinine.