Vaspin protects rats against myocardial ischemia/reperfusion injury (MIRI) through the TLR4/NF-κB signaling pathway.

The purpose of our study was to investigate the effect of vaspin on myocardial ischemia reperfusion injury (MIRI) and explore the underlying mechanism. The MIRI model was induced with 30 min of left anterior descending (LAD) occlusion followed by 24 h of reperfusion. In vivo, the rats were randomly divided into five groups: (1) Sham, (2) MIRI, (3) MIRI + vaspin (10 mg/kg), (4) MIRI + vaspin (20 mg/kg) and (5) MIRI + vaspin (40 mg/kg). In vitro, H9C2 cells were assigned to five groups: (1) control, (2) hypoxia-re-oxygenation (H/R), (3) H/R + vaspin (1 µg/ml), (4) H/R + vaspin (2 µg/ml) and (5) H/R + vaspin (4 µg/ml). As a result, vaspin ameliorated MIRI and H/R in a dose-dependent manner, as evidenced by triphenyl tetrazolium chloride (TTC) staining, TUNEL Assay and MTT assay, respectively, meanwhile vaspin decreased the levels of creatine phosphokinase-isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in rat serum, moreover, vaspin could reduce the contents of interleukin-1ß (IL-1ß), IL-18 and tumor necrosis factor alpha (TNF-α) in serum of rats and supernatant of H9C2 cells. Furthermore, vaspin down-regulated the expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor κB (NF-κB) in MIRI rats and H/R-induced H9C2 cells. In addition, patients with acute myocardial infarction (AMI) had lower levels of vaspin than patients without. In conclusion, vaspin might be a useful predictive biomarker in patients with AMI; furthermore, vaspin exhibits cardioprotective effects on MIRI which might act through inhibiting TLR4/NF-κB signaling pathway in vivo and in vitro.

Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K/AKT-Nrf2 pathway.

High altitude cerebral edema (HACE) is a severe type of acute mountain sickness (AMS) that occurs in response to a high altitude hypobaric hypoxic (HH) environment. GM1 monosialoganglioside can alleviate brain injury under adverse conditions including amyloid-ß-peptide, ischemia and trauma. However, its role in HACE-induced brain damage remains poorly elucidated. In this study, GM1 supplementation dose-dependently attenuated increase in rat brain water content (BWC) induced by hypobaric chamber (7600 m) exposurefor 24 h. Compared with the HH-treated group, rats injected with GM1 exhibited less brain vascular leakage, lower aquaporin-4 and higher occludin expression, but they also showed increase in Na+/K+-ATPase pump activities. Importantly, HH-incurred consciousness impairment and coordination loss also were ameliorated following GM1 administration. Furthermore, the increased oxidative stress and decrease in anti-oxidant stress system under the HH condition were also reversely abrogated by GM1 treatment via suppressing accumulation of ROS, MDA and elevating the levels of SOD and GSH. Simultaneously, GM1 administration also counteracted the enhanced inflammation in HH-exposed rats by muting pro-inflammatory cytokines IL-1ß, TNF-α, and IL-6 levels in serum and brain tissues. Subsequently, GM1 potentiated the activation of the PI3K/AKT-Nrf2 pathway. Cessation of this pathway by LY294002 reversed GM1-mediated inhibitory effects on oxidative stress and inflammation, and ultimately abrogated the protective role of GM1 in abating brain edema, cognitive and motor dysfunction. Overall, GM1 may afford a protective intervention in HACE by suppressing oxidative stress and inflammatory response via activating the PI3K/AKT-Nrf2 pathway, implying a promising agent for the treatment of HACE.