Resveratrol promotes macrophage M2 polarization and alleviates acute gouty arthritis in mice / 第二军医大学学报

ObjectiveTo investigate the preventive effect of resveratrol against acute gouty arthritis in mice and whether M2 polarization of macrophage mediates the effect. Methods Eighteen C57BL/6 mice were randomly divided into three groups (n=6): Sham group, model+solvent control group, and model+resveratrol group. The right hind limb ankle joint of mice in the sham group were treated with sterile normal saline. The right hind limb ankle joint of mice in the model+ solvent control group were treated with DMSO in advance and then with monosodium urate (MSU) crystals to establish acute gouty arthritis model. Mice in the model+resveratrol group were treated with resveratrol dissolved in DMSO in advance and then with MSU crystals to establish acute gouty arthritis model. The bilateral paw thickness of mice in each group was measured and H-E staining was used to observe the inflammation of synovial tissue of feet and metacarpal joints of mice in each group. The primary macrophages from abdominal cavity of normal mice were extracted, treated with resveratrol, and then stimulated with MSU crystals. The expression of M1-polarized macrophage markers inducible nitric oxide synthase (iNOS) protein and the inflammatory indexes tumor necrosis factor α (TNF-α) mRNA and interleukin 1β (IL-1β) mRNA were detected by Western blotting or qPCR. The expression of M2-polarized macrophage markers F4/80 and CD163 were detected by flow cytometry. Results Acute gouty arthritis model of mice was successfully established. The right hind limb thickness of mice in the model+resveratrol group was significantly lower than that in the model+solvent control group ([1.98±0.02] mm vs [2.49±0.12] mm, P?0.01). The infiltration area of neutrophils in synovial tissue of feet and metacarpal joints in mice of model+resveratrol group were also significantly reduced. In vitro, resveratrol significantly inhibited the expression of iNOS protein, TNF-α mRNA and IL-1β mRNA in primary peritoneal macrophages ( all P?0.01) and increased the percentage of F4/80+CD163+ in macrophages (P?0.01). Conclusion Resveratrol may effectively alleviate acute gouty arthritis in mice by promoting M2 polarization of macrophages and inhibiting the expression of inflammatory factors.

Adiponectin receptor agonist AdipoRon relieves endotoxin-induced acute hepatitis in mice / 中华医学杂志(英文版)

BACKGROUND@#Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored.@*METHODS@#BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups.@*RESULTS@#AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01; from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced.@*CONCLUSIONS@#These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis.

Adiponectin receptor agonist AdipoRon relieves endotoxin-induced acute hepatitis in mice / 中华医学杂志(英文版)

Background@#Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored.@*Methods@#BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups.@*Results@#AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01; from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced.@*Conclusions@#These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis.

Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats / 生理学报

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated. In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 μg/kg), Exenatide (10 μg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities.

Which is the best peri-operative anti-coagulative therapy of transverse sinus stenting for refractory idiopathic intracranial hypertension? / 中华医学杂志(英文版)

Treatment of refractory idiopathic intracranial hypertension (IIH) is a challenging problem. We reported a refractory IIH patient who manifested with typical intracranial hypertensive symptoms successfully treated with endovascular stent implantation. Pre-operative cerebrospinal fluid (CSF) opening pressure is 36 cmH2O. Cerebral angiography demonstrated a stenotic lesion located at the right transverse sinus (TS). The stenotic TS returned to its normal caliber and the pressure gradient deceased from 36 mmHg to 4 mmHg after the stent placement. The intracranial hypertensive symptoms resolved and one month later, the CSF opening pressure decreased to 14 cmH2O.

The quality of life and its influential factors in patients with 3 major rheumatic diseases / 中华物理医学与康复杂志

Objective To explore the quality of life (QOL) and its influential factors among patients with 3 major rheumatic diseases. Methods A total of 216 patients with rheumatic diseases (84 patients with systemic lu- pus erythematosus, SLE, 83 with rheumatoid arthritis, RA, and 49 with ankylosing spondylitis, AS) were recruited. The information with regard to their quality of life, sociopsychological factors and the evaluation of disease activity were obtained by using the medical outcomes study short form-36 (SF-36) and clinic documents. Results Patients with rheumatic diseases scored significantly lower with each subscale of SF-36 as compared to those of a healthy popu- lation in China (P