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Objectives: Abnormal rheological properties induce adverse effects during sepsis. This study sought to investigate the hypothesis that resveratrol (Res) improves blood rheological properties in rats following a lipopolysaccharide (LPS) challenge, and provide a novel approach for treatment of sepsis.Methods: The rats were intraperitoneally or intramuscularly injected with vehicle, LPS (8 mg/kg), Res (30 mg/kg), or both to yield four groups: control, Res, LPS, and LPS + Res. After 6 h of LPS and/or Res injection, the mean arterial pressure (MAP), regional blood flow, erythrocyte and leukocyte parameters, and blood viscosity were observed.Results: LPS administration had no significant effects on the erythrocyte parameters and plasma viscosity. LPS administration reduced the MAP, whole blood viscosity at low and medium shear rates, the blood flow in the spleen and kidney, and the leukocyte content in whole blood when compared to control group, and increased the myeloperoxidase (MPO) activity in lung. Treatment with Res alone had no effects on most of parameters observed except increasing the whole blood relative viscosity. However, Res treatment after LPS resulted in further decrease in whole blood viscosity at high and medium shear rates. Furthermore, Res treatment conversely decreased the red blood cell distribution width-CV, blood flow of stomach, whole blood relative viscosity and MPO activity in lung, and increased the leukocyte content, but did not restore LPS-induced decrease in MAP and the blood flow in the spleen and kidney.Conclusion: The Res treatment partly reduce the whole blood viscosity and regional blood flow, and increase WBC content in peripheral blood following the LPS challenge, suggesting a favorable role in expanding the quasi-sympathetic effects of LPS in blood viscosity at early stages.

Background: Hemorrhagic shock-induced ischemia and hypoxia elicit endoplasmic reticulum stress (ERS) that leads to cell apoptosis, tissue structural damage and organ dysfunction and failure. Stellate ganglion blockade (SGB) has been demonstrated to improve intestinal barrier dysfunction induced by hemorrhagic shock. The present study sought to investigate whether the beneficial effect of SGB on the intestinal mucosal barrier function is via suppression of ERS. Materials and methods: A conscious rat model of hemorrhagic shock (40 ±2 mmHg for 1 hour, followed by resuscitation) was established. The parameters reflecting intestinal morphology and intestinal mucosal barrier function including wet-dry ratio (W/D), intestinal permeability, D-lactic acid (D-LA) and intestinal fatty acid binding protein (I-FABP) in plasma, and expressions of ATF6α, PERK, and IRE1α in intestinal tissues were then observed. Furthermore, the effects of either SGB or ERS inhibitor, 4-phenylbutyric acid (4-PBA), on these parameters in rats with hemorrhagic shock were assessed. The effect of ERS agonist tunicamycin (TM) on the rats subjected with both SGB and hemorrhagic shock was also determined. Results: Either SGB or administration of ERS inhibitor, 4-PBA, alleviated hemorrhagic shock-induced adverse effects such as intestinal mucosal barrier dysfunction and excessive autophagy, which were characterized by damaged intestinal tissue, enhanced intestinal permeability and D-LA and I-FABP levels in plasma, and increased expressions of ATF6α, PERK, IRE1α in intestinal tissue. In contrast, administration of ERS agonist, TM, suppressed the beneficial effects of SGB on intestinal tissue and function during hemorrhagic shock. Conclusion: The SGB repairs intestinal mucosal barrier through suppression of ERS following hemorrhagic shock.

Purpose:To investigate the effect of mesenteric lymph drainage on the spleen injury and the expressions of inflammatory cytokines in splenic tissue in mice following hemorrhagic shock.Methods:Male C57 mice were randomly divided into the sham shock, shock and shock+drainage groups. The mice in both shock and shock+drainage groups suffered femoral artery bleeding, maintained mean arterial pressure (MAP) of 40±2 mmHg for 90 min, and were resuscitated. And mesenteric lymph drainage was performed in the shock+drainage group at the time of resuscitation. After three hours of resuscitation, the splenic tissues were harvested for the histological observation and protein and mRNA expression analysis of cytokines.Results:The spleen in the shock group revealed a significantly structural damage and increased mRNA expressions of MyD88 and TRAF6 and protein expressions of TIPE2, MyD88, TRIF and TRAF3 compared to the sham group. By contrast, the splenic pathological injury in the shock+drainage group was alleviated significantly, and the mRNA and protein expressions of TIPE2, MyD88, TRIF, TRAF3 and TRAF6 were significantly lower than those in the shock group.Conclusion:These results indicate that post-hemorrhagic shock mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and the expressions of inflammatory cytokines.

The aim is to investigate that 17β-estradiol (E2)/estrogen receptors (ERs) activation normalizes splenic CD4 + T lymphocytes proliferation and cytokine production through inhibition of endoplasmic reticulum stress (ERS) following hemorrhage. The results showed that hemorrhagic shock (hemorrhage through femoral artery, 38–42 mmHg for 90 min followed by resuscitation of 30 min and subsequent observation period of 180 min) decreased the CD4+ T lymphocytes proliferation and cytokine production after isolation and incubation with Concanavalin A (5 μg/mL) for 48 h, induced the splenic injury with evidences of missed contours of the white pulp, irregular cellular structure, and typical inflammatory cell infiltration, upregulated the expressions of ERS biomarkers 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6). Either E2, ER-α agonist propyl pyrazole triol (PPT) or ERS inhibitor 4-Phenylbutyric acid administration normalized these parameters, while ER-β agonist diarylpropionitrile administration had no effect. In contrast, administrations of either ERs antagonist ICI 182,780 or G15 abolished the salutary effects of E2. Likewise, ERS inducer tunicamycin induced an adverse effect similarly to that of hemorrhagic shock in sham rats, and aggravated shock-induced effects, also abolished the beneficial effects of E2 and PPT, respectively. Together, the data suggest that E2 produces salutary effects on CD4+ T lymphocytes function, and these effects are mediated by ER-α and GPR30, but not ER-β, and associated with the attenuation of hemorrhagic shock-induced ERS.

Objective: The aim of this study was to clarify the role of autophagy in stellate ganglion block (SGB) reversing posthemorrhagic shock mesenteric lymph (PHSML)-mediated vascular hyporeactivity.Methods: Hemorrhagic shock model in conscious rats was employed to observe the effects of SGB (0.2 ml of 0.25% ropivacaine hydrochloride hydrate) and autophagy inhibitor 3-methyladenine (3-MA; 30 mg/kg) on the vascular reactivity of second-order rat mesenteric arteries in vitro, while the effects of PHSML (1 ml/kg) and autophagy agonist rapamycin (Rapa, 10 mg/kg) on the beneficial effect of SGB were investigated. The cellular viability, contractility, and autophagy-related protein expressions in vascular smooth muscle cells (VSMCs) were detected following treatments of PHSML, PHSML obtained from the rats that underwent hemorrhagic shock plus SGB (PHSML-SGB), and PHSML plus 3-MA (5 mM), respectively.Results: Hemorrhagic shock significantly decreased the vascular reactivity to gradient norepinephrine (NE), which is reversed by the SGB treatment and 3-MA administration. On the contrary, PHSML intravenous infusion and Rapa administration inhibited the vascular contractile responses in rats that underwent hemorrhagic shock plus SGB treatment. PHSML treatment significantly inhibited the cellular viability and contractility in VSMCs, increased the expressions of LC3-II and Beclin 1, and decreased the expression of p62, along with opposite appearances in these indices following PHSML-SGB treatment. In addition, 3-MA counteracted the adverse roles of PHSML in these indices in VSMCs.Conclusion: SGB inhibits PHSML-mediated vascular hyporeactivity by reducing the excessive autophagy in VSMCs.

Vascular hypo-reactivity plays a critical role inducing organ injury during hemorrhagic shock. 17b-estradiol (E2) can induce vasodilation to increase blood flow in various vascular beds. This study observed whether E2 can restore vascular hypo-reactivity induced by hemorrhagic shock, and whether E2 effects are associated with RhoA-Rho kinase (ROCK)-myosin light chain kinase phosphatase (MLCP) pathway. The hemorrhagic shock model (40 AE 2 mm Hg for 1 h, resuscitation for 4 h) was established in ovary intact sham operation (OVI), ovariectomized (OVX), and OVX plus E2 supplement female mice. Intestinal microvascular loop was used to assess blood flow in vivo, mRNA expression and vascular reactivity in vitro. Hemorrhagic shock significantly reduced norepinephrine microvascular reactivity. Decreased microvascular reactivity was exacerbated by OVX and reversed by E2 supplement. U-46619 (RhoA agonist) increased microvascular reactivity, and C3 transferase (an ADP ribosyl transferase that selectively induces RhoA ribosylation) or Y-27632 (ROCK inhibitor) inhibited sham mice microvascular reactivity. Similarly, U-46619 increased microvascular reactivity in OVI and OVX mice following hemorrhagic shock, which was abolished by Y-27632 or concomitant incubation of okadaic acid (OA) (MLCP inhibitor) and Y-27632. In OVX plus E2 supplement mice with hemorrhagic shock, Y-27632 inhibited microvascular reactivity, which was abolished by concomitant U-46619 application. Lastly, hemorrhagic shock remarkably decreased intestinal loop blood flow, RhoA and ROCK mRNA expressions in vascular tissues in OVX females, but not in OVI females, which were reversed by E2 supplement. These results indicate that estrogen improves microvascular reactivity during hemorrhagic shock, and RhoA-ROCK signaling pathway may mediate E2 effects.

Background. Acute renal failure (ARF) is a common critical disorder. To decrease the mortality, it is important to prevent ARF from invading other organs in clinical setting. It is not known whether there is a dysfunction in pancreas during the pathogenesis of ARF. This study aimed to investigate the changes of morphology and function on pancreas in ARF rabbits. Methods. Sixty rabbits were randomly divided into four groups. The ARF model of groups 1 and 2 rabbits was established by hypodermic injection of 1% HgCl 2 (1.3 mL/kg) and intramuscular injection of 50% glyceritum (10 mL/kg), respectively. The control groups 1 and 2 were injected with same volume of normal saline. After 24 hours, urea and creatinine contents and pancreatic amylase (AMY) activities in serum were measured using an automatic biochemical analyzer; the insulin levels were measured with radioimmunoassay method. Moreover, morphological alterations were examined by light microscopy; free radicals, nitric oxide (NO), and nitric oxide synthase (NOS) in pancreas homogenate were determined. Results. Morphological study showed that there were vacuolar degeneration and necrosis in pancreas of ARF for both groups 1 and 2. Compared with corresponding control group, the AMY activity was significantly elevated, whereas the INS values were decreased significantly in ARF groups 1 and 2. Malonaldehyde, NO, and NOS in pancreas homogenate were significantly increased, and superoxide dismutase activity was decreased. Conclusion. These data suggested that there were morphological damage of pancreas and disturbance of pancreatic secretion function in rabbits with ARF. Free radicals-injury and NO excessive release may explain the observed dysfunction.