Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung inju...Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.展开更多
目的:观察耳甲区电针对脂多糖致内毒素血症模型大鼠血清炎性反应因子水平与肺组织核因子κB(NF-κB)表达的影响,探讨耳甲刺激对炎性反应的保护作用机制。方法:SD大鼠随机分为正常对照组、模型组、单纯耳甲电针组、耳甲电针组、迷走神经...目的:观察耳甲区电针对脂多糖致内毒素血症模型大鼠血清炎性反应因子水平与肺组织核因子κB(NF-κB)表达的影响,探讨耳甲刺激对炎性反应的保护作用机制。方法:SD大鼠随机分为正常对照组、模型组、单纯耳甲电针组、耳甲电针组、迷走神经刺激组、后三里组,每组12只。尾静脉注射脂多糖(5 mg/kg)复制内毒素血症模型。耳甲电针取双侧耳甲区,迷走神经刺激给予左侧颈部迷走神经电刺激,后三里组行双侧"后三里"电针,均为20 min。采用酶联免疫吸附法测定各组大鼠血清肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)水平,采用免疫印迹法测定各组肺组织NF-κB p 65蛋白表达。结果:与正常对照组相比,模型组TNF-α、IL-6水平明显升高(P<0.01),NF-κB p 65表达明显上调(P<0.01);单纯耳甲电针组NF-κB p 65表达明显上调(P<0.01)。与模型组相比,耳甲电针组和迷走神经刺激组TNF-α、IL-6水平明显下降(P<0.01),NF-κB p65表达明显下调(P<0.01);后三里组TNF-α水平明显下降(P<0.05)。与迷走神经刺激组相比,耳甲电针组IL-6水平显著升高(P<0.01),后三里组TNF-α、IL-6水平、NF-κB p 65表达显著升高(P<0.05,P<0.01)。与耳甲电针组相比,后三里组NF-κB p65表达显著升高(P<0.05)。结论:耳甲刺激能降低内毒素血症模型大鼠致炎因子水平,下调NF-κB蛋白表达,其效应与直接刺激迷走神经相似,说明耳甲刺激可能激活了胆碱能抗炎通路,从而启动抗炎效应。展开更多
The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of dige...The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.展开更多
为了研究miR-155在内毒素血症幼鼠肝损伤中的作用,将60只幼年Wistar鼠随机分为内毒素模型组、miR-155抑制组和空白组。模型组幼鼠通过腹腔内一次性注射LPS(20mg/kg)构建内毒素血症模型。miR-155抑制组幼鼠在腹腔内注射LPS后,再经尾静脉...为了研究miR-155在内毒素血症幼鼠肝损伤中的作用,将60只幼年Wistar鼠随机分为内毒素模型组、miR-155抑制组和空白组。模型组幼鼠通过腹腔内一次性注射LPS(20mg/kg)构建内毒素血症模型。miR-155抑制组幼鼠在腹腔内注射LPS后,再经尾静脉注射miR-155抑制剂(80mg/kg)。空白组幼鼠腹腔内注射等量生理盐水。各组建模2d后,进行肝脏生化指标、肝组织病理学、肝细胞凋亡、炎症蛋白、通路蛋白等项目的检测。实验结果表明,模型组幼鼠血液内miR-155的表达量、丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平显著高于空白组,miR-155抑制组ALT和AST水平显著低于模型组(P<0.05);模型组幼鼠肝细胞肥大且不规则,细胞排列紊乱,胞浆空泡增多;空白组幼鼠肝细胞排列整齐,仅少量肝细胞颗粒变性;miR-155抑制组肝细胞病理变化较少,细胞结构较完整;模型组细胞凋亡指数(apoptosis index,AI)、TNF-α和IL-10水平显著高于miR-155抑制组(P<0.05)和空白组(P<0.05);模型组Bcl-2/Bax显著低于空白组(P<0.05)和miR-155抑制组(P<0.05);模型组Ras同源基因A蛋白(Ras homolog gene family member A,RhoA)、Rho相关螺旋卷曲蛋白激酶1(Rho-associated coiled coil-forming protein kinase 1,ROCK1)和Rho相关螺旋卷曲蛋白激酶2(Rho-associated coiled coil-forming protein kinase 2,ROCK2)水平明显升高,而miR-155抑制组3种蛋白水平均显著下降。以上发现提示,miR-155可能通过调控Rho/ROCK通路参与内毒素血症幼鼠的肝损伤。展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30571787）.
文摘Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.
文摘目的:观察耳甲区电针对脂多糖致内毒素血症模型大鼠血清炎性反应因子水平与肺组织核因子κB(NF-κB)表达的影响,探讨耳甲刺激对炎性反应的保护作用机制。方法:SD大鼠随机分为正常对照组、模型组、单纯耳甲电针组、耳甲电针组、迷走神经刺激组、后三里组,每组12只。尾静脉注射脂多糖(5 mg/kg)复制内毒素血症模型。耳甲电针取双侧耳甲区,迷走神经刺激给予左侧颈部迷走神经电刺激,后三里组行双侧"后三里"电针,均为20 min。采用酶联免疫吸附法测定各组大鼠血清肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)水平,采用免疫印迹法测定各组肺组织NF-κB p 65蛋白表达。结果:与正常对照组相比,模型组TNF-α、IL-6水平明显升高(P<0.01),NF-κB p 65表达明显上调(P<0.01);单纯耳甲电针组NF-κB p 65表达明显上调(P<0.01)。与模型组相比,耳甲电针组和迷走神经刺激组TNF-α、IL-6水平明显下降(P<0.01),NF-κB p65表达明显下调(P<0.01);后三里组TNF-α水平明显下降(P<0.05)。与迷走神经刺激组相比,耳甲电针组IL-6水平显著升高(P<0.01),后三里组TNF-α、IL-6水平、NF-κB p 65表达显著升高(P<0.05,P<0.01)。与耳甲电针组相比,后三里组NF-κB p65表达显著升高(P<0.05)。结论:耳甲刺激能降低内毒素血症模型大鼠致炎因子水平,下调NF-κB蛋白表达,其效应与直接刺激迷走神经相似,说明耳甲刺激可能激活了胆碱能抗炎通路,从而启动抗炎效应。
文摘The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.
文摘为了研究miR-155在内毒素血症幼鼠肝损伤中的作用,将60只幼年Wistar鼠随机分为内毒素模型组、miR-155抑制组和空白组。模型组幼鼠通过腹腔内一次性注射LPS(20mg/kg)构建内毒素血症模型。miR-155抑制组幼鼠在腹腔内注射LPS后,再经尾静脉注射miR-155抑制剂(80mg/kg)。空白组幼鼠腹腔内注射等量生理盐水。各组建模2d后,进行肝脏生化指标、肝组织病理学、肝细胞凋亡、炎症蛋白、通路蛋白等项目的检测。实验结果表明,模型组幼鼠血液内miR-155的表达量、丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平显著高于空白组,miR-155抑制组ALT和AST水平显著低于模型组(P<0.05);模型组幼鼠肝细胞肥大且不规则,细胞排列紊乱,胞浆空泡增多;空白组幼鼠肝细胞排列整齐,仅少量肝细胞颗粒变性;miR-155抑制组肝细胞病理变化较少,细胞结构较完整;模型组细胞凋亡指数(apoptosis index,AI)、TNF-α和IL-10水平显著高于miR-155抑制组(P<0.05)和空白组(P<0.05);模型组Bcl-2/Bax显著低于空白组(P<0.05)和miR-155抑制组(P<0.05);模型组Ras同源基因A蛋白(Ras homolog gene family member A,RhoA)、Rho相关螺旋卷曲蛋白激酶1(Rho-associated coiled coil-forming protein kinase 1,ROCK1)和Rho相关螺旋卷曲蛋白激酶2(Rho-associated coiled coil-forming protein kinase 2,ROCK2)水平明显升高,而miR-155抑制组3种蛋白水平均显著下降。以上发现提示,miR-155可能通过调控Rho/ROCK通路参与内毒素血症幼鼠的肝损伤。
