Search

Objective: To investigate the protective effects and mechanisms of salvianolic acid B (Sal B) on hypoxia/reoxygenation H/R-induced renal tubular epithelial cell damage. Methods In vitro experimental cells were divided into the normal control Con groupthe Sal B+Con groupthe H/R groupthe Sal B+H/R group as well as the Con groupthe H/R groupSal B+H/R groupthe H/R+CC group and the H/R+Sal B+CC group. HK-2 cell viability was detected by the CCK-8 method. Cell lysates were collected to measure the levels of GSH and malondialdehyde MDA using an enzyme-linked immunosorbent assay. The expressions of p-AMPK GPX4 ACSL4 and FSP1 were detected by Western blot. The expression of ferroptosis markers GPX4 and ACSL4 proteins was detected by cell immunofluorescence while mitochondrial membrane potential and cell apoptosis were measured by flow cytometry.Results The results of the in vitro experiments showed that Sal B had no significant toxicity on normal HK-2 cell viability within the concentration range of 20-160 μmol/L P>0.05. Compared with the model group Sal B at concentrations of 20 40 and 80 μmol/L dose-dependently increased the viability of HK-2 cells P<0.01. Compared with the model group MDA content and GSH content of the H/R+Sal B group were decreased p-AMPK GPX4 and FSP1 protein expression levels were increased ACSL4 protein expression was decreased mitochondrial membrane potential was significantly increased and apoptosis rate was significantly decreased P<0.05. Compared with the H/R+Sal B group the FSP1 and GPX4 protein expression level in the H/R+AMPK group was decreased the ACSL4 protein expression level was increased P< 0.05 and the mitochondrial membrane potential was significantly decreased P<0.05 and the addition of Sal B could reverse this situation P<0.05.Conclusion Salvianolic acid B can alleviate I/R-induced AKI and its mechanism may involve the activation of the AMPK pathway to mitigate ferroptosis in renal tubular epithelial cells. [ABSTRACT FROM AUTHOR]

Author(s): Wanyu Wang [sup.1] , Xiaoshuang Zhou [sup.1] , Xinyang Liao [sup.2] , Bin Liu [sup.1] , Hai Yu [sup.1] Author Affiliations: (Aff1) 0000 0004 1770 1022, grid.412901.f, Department of [...], Prophylactic use of levosimendan in cardiac surgery remains controversial and no meta-analysis has been done exclusively about that in patients undergoing coronary artery bypass graft (CABG) surgery. We conducted this systematic review and meta-analysis of levosimendan in CABG using PubMed, Embase, Scopus, and Cochrane Library (till April 20, 2018). Two-hundred and forty manuscripts were identified and 21 randomized trials (1727 patients in total) investigating the effect of levosimendan on the patients undergoing CABG surgery were finally included in this analysis. We found that levosimendan was an effective, well-tolerated inotropic agent in CABG, which was associated with a significantly reduced mortality rate [odds ratio (OR) 0.43, 95% confidence interval (CI) (0.26, 0.71), p = 0.001, I.sup.2 = 0%] and postoperative atrial fibrillation [OR 0.50, 95% CI (0.26, 0.97), p = 0.04, I.sup.2 = 76%], but a higher incidence of hypotension [OR 2.26, 95% CI (1.05, 4.85), p = 0.04, I.sup.2 = 79%]. Subgroup analyses revealed that such a benefit was mainly observed in the isolated CABG, the preoperative administration, with-bolus and on-pump subgroups. More high-quality and well-designed prospective studies are needed to confirm or disprove our findings in future.

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease associated with autoantibody formation. Lupus nephritis (LN) is one of the most severe organ manifestations of SLE. The inflammatory response is a key factor in kidney injury, and the NLRP3 inflammasome is frequently associated with the pathogenesis of LN. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD +)-dependent histone deacetylase, is a promising therapeutic target for preventing renal injury. However, the mechanism of SIRT1 in LN remains unclear. Here, we aimed to investigate the mechanism by which SIRT inhibits the NLRP3 inflammasome to slow the progression of LN. We detected the expression of SIRT1 and the infiltration of macrophages in MRL/lpr mice; the results showed that the expression of SIRT1 was decreased, and the symptoms of lupus nephritis were relieved after the use of resveratrol, which upregulated SIRT1. In vitro studies showed that after lipopolysaccharide (LPS) stimulation, SIRT1 expression decreased, and the NLRP3 inflammasome was activated. Upregulation of SIRT1 inhibits NLRP3 inflammasome activation and assembly by interfering with two signalling pathways. First, SIRT1 affects NF-κB expression, transcription, and inflammatory cytokine expression. Second, SIRT1 modulates calcium influx induced by transient receptor potential channel M2 (TRPM2), which could be partly due to the inhibition of reactive oxygen species (ROS) production. Our findings suggest that upregulated SIRT1 inhibits the NLRP3 inflammasome to slow the progression of lupus nephritis by regulating NF-κB and ROS/TRPM2/Ca2+ channels. This study reveals a new anti-inflammatory mechanism of SIRT1, suggesting that SIRT1 may be a potential therapeutic target for the prevention of LN. [ABSTRACT FROM AUTHOR]