Sodium butyrate ameliorates sepsis-associated lung injury by enhancing gut and lung barrier function in combination with modulation of CD4+Foxp3+ regulatory T cells.

Sepsis-associated lung injury often coexists with intestinal dysfunction. Butyrate, an essential gut microbiota metabolite, participates in gut-lung crosstalk and has immunoregulatory effects. This study aims to investigate the effect and mechanism of sodium butyrate (NaB) on lung injury. Sepsis-associated lung injury was established in mice by cecal ligation and puncture (CLP). Mice in treatment groups received NaB gavage after surgery. The survival rate, the oxygenation index and the lung wet-to-dry weight (W/D) ratio were calculated respectively. Pulmonary and intestinal histologic changes were observed. The total protein concentration in bronchoalveolar lavage fluid (BALF) was measured, and inflammatory factors in serum and BALF were examined. Diamine oxidase (DAO), lipopolysaccharide (LPS), and surfactant-associated protein D (SP-D) levels in serum and amphiregulin in lung tissue were assessed. Intercellular junction protein expression in the lung and intestinal tissues were examined. Changes in immune cells were analyzed. NaB treatment improved the survival rate, the oxygenation index and the histologic changes. NaB decreased the W/D ratio, total protein concentration, and the levels of proinflammatory cytokines, as well as SP-D, DAO and LPS, while increased the levels of anti-inflammatory cytokines and amphiregulin. The intercellular junction protein expression were improved by NaB. Furthermore, the CD4+/CD8+ T-cell ratio and the proportion of CD4+Foxp3+ regulatory T cells (Tregs) were increased by NaB. Our data suggested that NaB gavage effectively improved the survival rate and mitigated lung injury in CLP mice. The possible mechanism was that NaB augmented CD4+Foxp3+ Tregs and enhanced the barrier function of the gut and the lung.

Stellate ganglion block potentially ameliorates postoperative cognitive decline in aged rats by regulating the neuroendocrine response to stress.

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The strong stress response causing by surgical trauma can induce POCD. We hypothesized that stellate ganglion block (SGB) can provide the neuroprotection to POCD by regulating the neuroendocrine response. Methods: Sprague-Dawley male rats, 18-20 months old and weighing 550-650 g were assigned into four groups: sham surgery group (Sham), sham surgery + saline group (Sham + NS), surgery group (Surgery), and surgery + SGB group (Surgery + SGB). The change of body weight, heart rate variability analysis, behavior testing, neuronal damage, inflammatory response, neuroendocrine hormone level were evaluated by their corresponding methods. Results: The results showed that SGB can reduce the number of both types of errors in the postoperative eight-arm maze assay, attenuate neural structural damage, inhibit neuroapoptosis, suppress inflammatory responses, increase the release of neurotrophic factors, accelerate postoperative weight recovery, and promote postoperative recovery in rats. Most importantly, SGB reduced the level of neuroendocrine hormone of TH, Cyp11b1, CRH, and SGB also activated dorsal motor nucleus of vagus (detected by c-fos immunohistochemistry). Conclusions: Our findings indicated that SGB could be a neuroprotective therapy for the cognitive dysfunction induced by exploratory laparotomy model of POCD, which might be attributable for balancing the autonomic nervous system, regulating hypothalamic-pituitary-adrenal (HPA) axis system.

Protection of Myocardial Ischemia-Reperfusion by Therapeutic Hypercapnia: a Mechanism Involving Improvements in Mitochondrial Biogenesis and Function.

Previous studies proposed that acidic reperfusion may be a protective strategy for myocardial ischemia-reperfusion therapy with potential of clinical transformation. In this study, we investigated whether therapeutic hypercapnia could mimic acidosis postconditioning in isolated hearts with a 30-min left coronary artery ligation-reperfusion model in rats. Therapeutic hypercapnia (inhalation 20% CO2 for 10 min) is cardioprotective with a strict therapeutic time window and acidity: it reduced the infarct ratio and serum myocardial enzyme and increased the myocardial ATP content. Furthermore, mitochondrial morphology damage, the loss of mitochondrial membrane potential, and the formation of mitochondrial permeability transition pore were effectively inhibited, indicating the improvements in mitochondrial function. The expression of the mitochondrial biogenesis regulators was upregulated simultaneously. These findings indicated therapeutic hypercapnia in animals can mimic ex vivo acidosis postconditioning to alleviate myocardial ischemia-reperfusion injury. The effect is related to improvement in mitochondrial function and regulation of the mitochondrial biogenesis pathway.