Outcome Improvement for Hypothermic Machine Perfusion Versus Cold Storage for Kidneys From Cardiac Death Donors.

Organ shortage has led to an increased use of kidneys from cardiac death donors (DCDs), but controversies about the methods of organ preservation still exist. This study aims to compare the effect of machine perfusion (MP) and cold storage (CS) in protecting kidneys harvested from DCDs. 141 kidney pairs from DCDs between July 2010 and July 2015 were included in this randomized controlled study. One kidney from each donor was randomly assigned to MP and the contralateral kidney was assigned to CS. Delayed graft function (DGF) rate, resistance index of renal arteries, early renal function, and survival rates were used to estimate the effect of preservation. The results showed that MP decreased the rate of DGF from 33.3 to 22.0% (P = 0.033). Ultrasound of the kidneys within 48 h after transplantation showed that the resistance index of renal main artery (0.673 ± 0.063 vs. 0.793 ± 0.124, P < 0.001), sub segmental artery (0.66 ± 0.062 vs. 0.764 ± 0.077, P < 0.001) and interlobular artery (0.648 ± 0.056 vs. 0.745 ± 0.111, P = 0.023) were all significantly lower in the MP group than those in the CS group. Furthermore, compared to the CS group, in the first 7 days following transplantation, the median urine volume was significantly higher (4080 mL vs. 3000 mL, P = 0.047) in kidneys sustained using MP and the median serum creatinine was remarkably lower (180 µmol/L vs. 390 µmol/L, P = 0.024). More importantly, MP group had higher 1- and 3-year graft survival rates (98% vs. 93%, P = 0.026; 93% vs. 82%, P = 0.036, respectively). Hypothermic MP improved the outcomes of DCD kidney transplantation.

Endoplasmic reticulum stress induces liver cells apoptosis after brain death by suppressing the phosphorylation of protein phosphatase 2A.

The present study aimed to investigate whether brain death (BD) induces the activation of endoplasmic reticulum stress (ERS) and protein phosphatase 2A (PP2A), and reveal the possible association with BD­induced liver cell apoptosis. A total of 30 healthy adult male Sprague­Dawley rats were randomized into three groups: Sham­operated group (S), BD group and 4­phenylbutyric acid group (BD + 4­PBA), with 10 rats in each group. All rats were anesthetized. The model of BD was established by inflating a balloon catheter that was placed into the extradural space after anesthesia. 4­PBA was administered via an intraperitoneal injection when the BD model was established. Anesthesia of the S group of rats was maintained for 6 h. Liver tissues were harvested after 6 h of BD. HE staining was used to evaluate the damage of liver. Terminal deoxynucleotidyl transferase­mediated 2'­deoxyuridine 5'­triphosphate nick­end labeling staining was used to observe the apoptosis of liver cells. Activation of ERS and PP2A was examined by western blotting and immunohistochemical staining. We reported that the apoptosis of liver cells after BD was significantly promoted than in the S group. Activation of ERS and PP2A was induced in the BD group when compared with S group. Phosphorylation of PP2A was suppressed in BD group. Application of 4­PBA decreased the activation of ERS and apoptosis rate compared with the BD group. In addition, activation of PP2A in the BD + 4­PBA group was decreased due to the reduction of PP2A phosphorylation compared with the BD group, but the levels were higher than in the S group. (P<0.05). In summary, our results indicated that BD induced ERS, then activated PP2A by suppressing the phosphorylation of PP2A, resulting in the apoptosis of liver cells.

Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3ß/Nrf2 Pathway in Mice.

AIMS: Ischemic postconditioning (IPO) has a strong protective effect against intestinal ischemia-reperfusion (IIR) injury that is partly related to autophagy. However, the precise mechanisms involved are unknown. METHODS: C57BL/6J mice were subjected to unilateral IIR with or without IPO. After 45 min ischemia and 120 min reperfusion, intestinal tissues and blood were collected for examination. HE staining and Chiu's score were used to evaluate pathologic injury. We test markers of intestinal barrier function and oxidative stress. Finally, we used WB to detect the expression of key proteins of autophagy and the Akt/GSK-3ß/Nrf2 pathway. RESULTS: IPO significantly attenuated IIR injury. Expression levels of LC3 II/I, Beclin-1, and p62 were altered during IIR, indicating that IPO enhanced autophagy. IPO also activated Akt, inhibited GSK-3ß/Nrf2 pathway. CONCLUSION: Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3ß, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury.ß/Nrf2 pathway.