BackgroundIschemia/reperfusion injury plays a crucial role in renal transplantation, and represents a significant risk factor for acute renal failure and delayed graft function. The pathophysiological contribution of endoplasmic reticulum and mitochondria stress to ischemia/reperfusion injury has also been highlighted. Berberine (BBR) has been showed to attenuate ischemia/reperfusion injury by inhibiting oxidative stress. The study was carried out to investigate whether the pretreatment of BBR could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting mitochondria stress and endoplasmic reticulum stress pathways.MethodsThe cultured human renal proximal tubular cell line HK-2 cells were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 3 h reoxygenation (5% CO2, 21% O2, 74% N2). And BBR was added to the culture medium 2h prior to the treatment. Then the cell viability, oxidative stress level, morphological change of apoptosis and apoptotic rate were determined. In addition, Western blot analysis was performed to identify the expression of apoptotic pathway parameters, including Bcl-2, Bax and cytochrome C involved in mitochondrial-dependent pathway and ER stress hallmarks such as glucose-regulated protein 78 and CCAAT/enhancer binding protein homologous protein.ResultsH/R produced dramatic injuries in HK-2 cells. The cell viability and the oxidative stress level in group H/R was significantly decreased. The classical morphological change of apoptosis was found, while the apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased (p<0.05). Administration of BBR significantly inhibited these H/R induced changes (p<0.05).ConclusionThis study revealed that BBR pretreatment serves a protective role against H/R induced apoptosis of human renal proximal tubular cells, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress pathways.
Background High mobility group box 1 (HMGB1) protein is one of the main risk factors for pediatric acute respiratory distress syndrome (PARDS) after living donor liver transplantation (LDLT). However, studies of the relationship between HMGB1 and PARDS are lacking. We evaluated the link between anomalies of intraoperative serum HMGB1 and PARDS in pediatric LDLT recipients with biliary atresia during the first week after transplant. Methods Data for 210 pediatric patients with biliary atresia who underwent LDLT between January 2018 and December 2021 were reviewed retrospectively. The main measure was serum HMGB1 levels 30 min after reperfusion, while the outcome was early PARDS after LDLT. Data including pretransplant conditions, laboratory indexes, variables of intraoperation, clinical complications, and outcomes after LDLT were analyzed for each patient. Univariate analysis of PARDS and multivariate logistic regression analyses of serum HMGB1 levels at 30 min in the neohepatic phase in the presence of PARDS were conducted to examine the potential associations. Subgroup interaction analyses and linear relationships between intraoperative serum HMGB1 levels and PARDS were also performed. Results Among the participants, 55 had PARDS during 7 days after LDLT, including four in the first HMGB1 tertile (4.3–8.1 pg/mL), 18 in the second tertile (8.2–10.6 pg/mL), and 33 in the third tertile (10.6–18.8 pg/mL). The nonadjusted association between intraoperative HMGB1 levels and PARDS was positive (odds ratio 1.41, 95% confidence intervals 1.24–1.61, P < 0.0001). The association remained unchanged after adjustment for age, weight, pretransplant total bilirubin, albumin, graft cold ischemia time, and intraoperative blood loss volume (odds ratio 1.28, 95% confidence interval 1.10–1.49, P = 0.0017). After controlling for potential confounders, the association between intraoperative HMGB1 levels and PARDS remained positive, as well as in the subgroup analyses. Conclusions Serum HMGB1 levels at 30 min after reperfusion were positively associated with early PARDS among pediatric patients with biliary atresia who had undergone LDLT. Identifying such patients early may increase the efficacy of perioperative respiratory management.
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