Sirtuin 3 (SIRT3) improves sevoflurane-induced postoperative cognitive impairment by regulating mitochondrial oxidative stress.

One of the most prevalent co-operative disorders is postoperative cognitive dysfunction (POCD), however, its pathogenesis remains unclear. Thus, the aim of this work was to evaluate SIRT3's impact on cognitive decline in aged mice under anesthesia. Adeno-associated virus SIRT3 vector (AAV-SIRT3) or empty vector (AAV-VEH) was injected into the hippocampal region of aged mice after sevoflurane induction in order to upregulate the expression of SIRT3. The expression levels of SIRT3, pro-inflammatory cytokines, and apoptotic factors in hippocampus tissues were identified by PCR, Western blotting, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA), and the cognitive function of mice was assessed. The SIRT3 expression was down-regulated in the hippocampal tissue of anesthetized mice. SIRT3 overexpression can improve the learning and memory ability, reduce the escape latency, and increase the residence time in the platform and platform crossing ability of mice. The overexpression of SIRT3 in hippocampus can reduce the oxidative stress response and inflammatory response induced by anesthesia in mice, increase the superoxide dismutase (SOD) expression level, and decrease the expression level of MDA and inflammatory factors in hippocampus. In addition, SIRT3 overexpression can also reduce anesthetic-induced hippocampal cell apoptosis. By reducing the hippocampus mitochondrial oxidative stress response, SIRT3 plays a significant role in the pathophysiology of POCD in mice and is a potential target for POCD treatment and diagnosis.

Synthetic LXR agonist T0901317 attenuates lipopolysaccharide-induced acute lung injury in rats.

OBJECTIVE: To investigate the potential role of synthetic liver X receptors (LXRs) agonists T0901317 in lung of rats with acute lung injury induced by lipopolysaccharide (LPS). METHODS: Rats infused with LPS served as acute lung injury (ALI) models. Specific mRNA was quantified by semi-quantitative reverse transcription polymerase (RT-PCR) and protein expression by western blotting. Inflammatory cytokine and MPO activity assays were studied by ELISA. Histopathology analysis was evaluated by hematoxylin and eosin. RESULTS: The expressions of LXRα and LXRß were gradually decreased after LPS challenge. T0901317 pretreatment efficiently reduced the production of TNF-α, IL-1ß, and IL-6, while elevated the level of IL-10 in BALF of rats with ALI. T0901317 also decreased the number of inflammatory cells and the concentration of total proteins in the BALF. Compared with the LPS group, rats with ALI which were pretreated with T0901317 had lower pulmonary tissue MPO activity and lightened histopathologic changes of lung. Furthermore, the expressions of NF-κB and ICAM-1 were markedly reduced after T0901317 administration. CONCLUSION: The expressions of LXRs were significantly decreased and synthetic agonist T0901317 suppresses lung inflammatory responses and lightened histopathologic changes of lung in rats with ALI. The mechanisms of this action for T0901317 may associate with the inhibition of NF-κB activation and downregulation of adhesion molecules ICAM-1 gene.