Omega-3 polyunsaturated fatty acids alleviates lung injury mediated by post-hemorrhagic shock mesenteric lymph.

Severe hemorrhage-induced acute lung injury (ALI) remains the major contributor to critical patient mortality and is associated with posthemorrhagic shock mesenteric lymph (PHSML) return. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) play overall protection on acute hemorrhage, but a reliable mechanism needs to be identified. The aims of this study were to investigate the role of ω-3 PUFAs in alleviating ALI and whether is related to the endotoxin contained in PHSML. Mesenteric lymph was harvested from rats subjected to hemorrhagic shock (hemorrhage-induced hypotension of 40 ± 2 mmHg for 90 min plus by resuscitation) or sham shock. The effect of ω-3 PUFAs on pulmonary function, water content, morphology, and LBP, CD14, TNF-α, and IL-6 levels were observed in rats subjected to hemorrhagic shock, while the effect of PHSML intravenous infusion on the beneficial effect of ω-3 PUFAs also was investigated. In addition, the effect of ω-3 PUFAs on the endotoxin contents in mesenteric lymph were detected. Hemorrhagic shock-induced ALI was characterized by increased functional residual capacity (FRC), lung resistance (RI), inspiratory capacity (IC), respiratory frequency, water contents and structural damage, along with increases in LBP, IL-6, and TNF-α. ω-3 PUFAs treatment reduced FRC, RI, IC, frequency, water contents, LBP, IL-6, TNF-α, and alleviated morphological damage. In contrast, PHSML infusion abolished the advantageous effects of ω-3 PUFAs on the above indices and CD14. Furthermore, the endotoxin level of PHSML was significantly enhanced, but declined following ω-3 PUFAs administration. These findings together suggested that treatment with ω-3 PUFAs ameliorates hemorrhagic shock-induced ALI, which is associated with reduced endotoxin contained in PHSML.

Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway.

The aim of the present study was to identify whether sepsis-induced vascular hyporeactivity is associated with microcirculation disturbance and multiple organ injuries. The current study assessed the impact of resveratrol (Res) treatment on lipopolysaccharide (LPS) challenge mediated vascular hyporeactivity. Effects of Res treatment (30 mg/kg; i.m.) at 1 h following LPS stimulation (5 mg/kg; i.v.) on the survival time, mean arterial pressure (MAP), and maximal difference of MAP (ΔMAP) to norepinephrine (NE; 4.2 µg/kg) in mice were observed. The reactivity to gradient NE of isolated mesenteric arterioles and the association with the RhoA-RhoA kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway were investigated by myography, and the signaling molecule protein levels were assessed using ELISA. Res treatment prolonged the survival time of mice subjected to LPS challenge, but did not prevent the LPS-induced hypotension and increase in ΔMAP. Res treatment and RhoA agonist U-46619 incubation prevented LPS-induced vascular hyporeactivity ex vivo, which were suppressed by incubation with ROCK inhibitor Y-27632. LPS-induced vascular hyporeactivity was not affected by the MLCP inhibitor okadaic acid incubation, but was further downregulated by the co-incubation of OA plus Y-27632. The inhibiting effect of Y-27632 on Res treatment was eradicated by incubation with U-46619. Furthermore, RhoA inhibitor C3 transferase did not significantly inhibit the enhancing role of Res treatment, which was further increased by U-46619 plus C3 transferase co-incubation. In addition, Res treatment eradicated the LPS-induced decreases in p-RhoA and p-Mypt1 levels and increases in MLCP levels. The results of the present study indicate that post-treatment of Res significantly ameliorates LPS-induced vascular hyporeactivity, which is associated with the activation of the RhoA-ROCK-MLCP pathway.