BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant ...BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed. RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF. CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.展开更多
<em>Markhamia tomentosa</em> (Benth.) K. Schum. (<em>Mt</em>) is a Cameroonian medicinal plant, traditionally used to treat painful and inflammatory illness. This study aimed to examine the eff...<em>Markhamia tomentosa</em> (Benth.) K. Schum. (<em>Mt</em>) is a Cameroonian medicinal plant, traditionally used to treat painful and inflammatory illness. This study aimed to examine the effects of methanol leaves extract (MLE) of <em>Mt</em> in <span style="white-space:nowrap;">D</span>-galactosamine (<span style="white-space:nowrap;">D</span>-GaIN)/lipopolysaccharide (LPS)-induced liver injury. The MLE (100 and 200 mg/kg), Ascorbic acid (10 mg/kg) and distilled water were administered 12 h and 1 h before intraperitoneal injection of <span style="white-space:nowrap;">D</span>-GaIN (10 mg/mouse)/LPS (0.1 <em>μ</em>g/g). Animals were sacrificed 6 h after <span style="white-space:nowrap;">D</span>-GalN/LPS challenge. Liver injury was assessed biochemically by determination of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), superoxide dismutase (SOD) and catalase activities. Malondialdehyde (MDA), reduced glutathione (GSH), nitrites, total protein and bilirubin levels were explored. Histopathological examination of liver tissue was also performed. Liver enzymes (ALAT, ASAT, ALP) activity, nitrites, MDA and bilirubin levels were increased, while protein level, SOD and catalase activities were significantly reduced by <span style="white-space:nowrap;">D</span>-GalN/LPS administration. MLE (100 or 200 mg/kg) protected mice against <span style="white-space:nowrap;">D</span>-GalN/LPS-induced death. In addition, the plant extract significantly reduced ALAT and ALP activity, exhibiting 23.00% and 62.20% protection, respectively. SOD activity and total protein were significantly (p < 0.05) increased by the plant extract. Total bilirubin and MDA levels were reduced (p < 0.01) by 37.75% and 62.79%, respectively in animal treated with MLE. Histological analysis of liver sections showed that MLE (100 or 200 mg/kg) protected mice against <span style="white-space:nowrap;">D</span>-GaIN/LPS-induced liver injury. The obtained results showed that MLE of <em>Mt </em>may possess hepatoprotective effects. Protection afforded by MLE against <span style="white-space:nowrap;">D</span>-GalN/LPS-induced fulminant liver injury may result from reduction of oxidative stress.展开更多
目的肺表面活性物质蛋白D(SP-D)被认为是急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)有价值的生物指标。该研究旨在探讨幼鼠ALI时及地塞米松干预后肺组织SP-D的变化。方法144只SD大鼠被随机分为正常对照组、肺损伤组和地塞米松治疗组。...目的肺表面活性物质蛋白D(SP-D)被认为是急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)有价值的生物指标。该研究旨在探讨幼鼠ALI时及地塞米松干预后肺组织SP-D的变化。方法144只SD大鼠被随机分为正常对照组、肺损伤组和地塞米松治疗组。腹腔内注射脂多糖(LPS,4 mg/kg)建立急性肺损伤模型,正常对照组注射等量生理盐水,治疗组于注射LPS 1小时后注射地塞米松(5 mg/kg)。LPS注射后6,12,24,36,48,72 h每组各处死8只大鼠。用Western blot方法测定肺组织SP-D的相对含量。结果与正常对照组相比,ALI组在注射LPS后36,48,72 h SP-D含量明显下降(P<0.01),在48 hrs达最低点(0.92±0.11 vs 3.27±0.52)。地塞米松治疗组于注射LPS后36,48,72 h SP-D含量明显高于ALI组(P<0.01),6,12,24,36和48 h与对照组相比差异无显著性,72 h差异有显著性(P<0.05)。结论急性肺损伤早期幼鼠肺组织SP-D含量降低。早期应用地塞米松能使ALI肺组织下降的SP-D明显上升。展开更多
基金supported by grants from the 973 Program of China (2007CB512902)the National Natural Science Foundation of China (30972622)the National Science and Technology Major Project of China (2008ZX10002-006)
文摘BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed. RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF. CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.
文摘<em>Markhamia tomentosa</em> (Benth.) K. Schum. (<em>Mt</em>) is a Cameroonian medicinal plant, traditionally used to treat painful and inflammatory illness. This study aimed to examine the effects of methanol leaves extract (MLE) of <em>Mt</em> in <span style="white-space:nowrap;">D</span>-galactosamine (<span style="white-space:nowrap;">D</span>-GaIN)/lipopolysaccharide (LPS)-induced liver injury. The MLE (100 and 200 mg/kg), Ascorbic acid (10 mg/kg) and distilled water were administered 12 h and 1 h before intraperitoneal injection of <span style="white-space:nowrap;">D</span>-GaIN (10 mg/mouse)/LPS (0.1 <em>μ</em>g/g). Animals were sacrificed 6 h after <span style="white-space:nowrap;">D</span>-GalN/LPS challenge. Liver injury was assessed biochemically by determination of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), superoxide dismutase (SOD) and catalase activities. Malondialdehyde (MDA), reduced glutathione (GSH), nitrites, total protein and bilirubin levels were explored. Histopathological examination of liver tissue was also performed. Liver enzymes (ALAT, ASAT, ALP) activity, nitrites, MDA and bilirubin levels were increased, while protein level, SOD and catalase activities were significantly reduced by <span style="white-space:nowrap;">D</span>-GalN/LPS administration. MLE (100 or 200 mg/kg) protected mice against <span style="white-space:nowrap;">D</span>-GalN/LPS-induced death. In addition, the plant extract significantly reduced ALAT and ALP activity, exhibiting 23.00% and 62.20% protection, respectively. SOD activity and total protein were significantly (p < 0.05) increased by the plant extract. Total bilirubin and MDA levels were reduced (p < 0.01) by 37.75% and 62.79%, respectively in animal treated with MLE. Histological analysis of liver sections showed that MLE (100 or 200 mg/kg) protected mice against <span style="white-space:nowrap;">D</span>-GaIN/LPS-induced liver injury. The obtained results showed that MLE of <em>Mt </em>may possess hepatoprotective effects. Protection afforded by MLE against <span style="white-space:nowrap;">D</span>-GalN/LPS-induced fulminant liver injury may result from reduction of oxidative stress.
文摘目的肺表面活性物质蛋白D(SP-D)被认为是急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)有价值的生物指标。该研究旨在探讨幼鼠ALI时及地塞米松干预后肺组织SP-D的变化。方法144只SD大鼠被随机分为正常对照组、肺损伤组和地塞米松治疗组。腹腔内注射脂多糖(LPS,4 mg/kg)建立急性肺损伤模型,正常对照组注射等量生理盐水,治疗组于注射LPS 1小时后注射地塞米松(5 mg/kg)。LPS注射后6,12,24,36,48,72 h每组各处死8只大鼠。用Western blot方法测定肺组织SP-D的相对含量。结果与正常对照组相比,ALI组在注射LPS后36,48,72 h SP-D含量明显下降(P<0.01),在48 hrs达最低点(0.92±0.11 vs 3.27±0.52)。地塞米松治疗组于注射LPS后36,48,72 h SP-D含量明显高于ALI组(P<0.01),6,12,24,36和48 h与对照组相比差异无显著性,72 h差异有显著性(P<0.05)。结论急性肺损伤早期幼鼠肺组织SP-D含量降低。早期应用地塞米松能使ALI肺组织下降的SP-D明显上升。
