甜菜碱对大鼠肝纤维化的保护作用研究

目的观察甜菜碱对复合致病因素诱导肝纤维化大鼠的保护作用。方法复合致病因素法诱导制备肝纤维化大鼠模型,观察灌服甜菜碱对肝纤维化大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、内毒素(ET)、同型半胱氨酸(Hcy)、透明质酸(HA)、层粘连蛋白(LN)、IV胶原蛋白(IV-C)、Ⅲ型前胶原蛋白(PC-Ⅲ)及肝组织肿瘤坏死因子α(TNF-α)、一氧化氮(NO)、过氧亚硝酸盐阴离子(ONOO-)、丙二醛(MDA)的变化,并采用HE和VG染色分别观察肝损伤和肝纤维化情况。结果大鼠肝纤维化模型复制成功。给与三个剂量的甜菜碱后,肝组织病理损伤改善。反映大鼠肝功能(ALT、AST)及肝纤维化指标(HA、LN、IV-C)的水平不同程度降低。血清内毒素、肝组织NO、MDA水平亦明显降低。同时Hcy及ONOO-在中、高剂量组明显降低,而TNF-α的降低在高剂量组中也具有明显的统计学差异。结论甜菜碱可抑制复合因素诱导的大鼠肝纤维化,其作用可能是通过降低大鼠体内高同型半胱氨酸、调节炎性细胞因子和氧化应激实现的。     

Postprandial Effect of a High-Fat Meal on Endotoxemia in Arab Women with and without Insulin-Resistance-Related Diseases

This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m²), 24 overweight/obese (referred to as overweight-plus (overweight⁺)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m²) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m²). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12–14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight⁺ and T2DM than the controls (p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.     

High mobility group 1 B-box mediates activation of human endothelium

OBJECTIVES: Severe sepsis and septic shock is a consequence of a generalized inflammatory systemic response because of an invasive infection that may result in acute organ dysfunction. Mortality is high despite access to modern intensive care units. The nuclear DNA binding protein high mobility group 1 (HMGB1) protein has recently been suggested to act as a late mediator of septic shock via its function as a macrophage-derived pro-inflammatory cytokine (J Exp Med 2000; 192: 565, Science1999; 285: 248). We investigated the pro-inflammatory activities of the A-box and the B-box of HMGB1 on human umbilical venular endothelial cells (HUVEC). DESIGN: The HUVEC obtained from healthy donors were used for experiments. Recombinant human full-length HMGB1, A-box and B-box were cloned by polymerase chain reaction (PCR) amplification from a human brain quick-clone cDNA. The activation of HUVEC was studied regarding (i) upregulation of adhesion molecules, (ii) the release of cytokines and chemokines, (iii) the adhesion of neutrophils to HUVEC, (iv) the activation of signalling transduction pathways and (v) the involvement of the receptor for advanced glycation end-products (RAGE). RESULTS: The full-length protein and the B-box of HMGB1 dose-dependently activate HUVEC to upregulate adhesion molecules such as ICAM-1, VCAM-1 and E-selectin and to release IL-8 and G-CSF. The activation of HUVEC could be inhibited to 50% by antibodies directed towards the RAGE. HMGB1-mediated HUVEC stimulation resulted in phosphorylation of the ELK-1 signal transduction protein and a nuclear translocation of p65 plus c-Rel, suggesting that HMGB1 signalling is regulated in endothelial cells through NF-kappaB. CONCLUSIONS: The HMGB1 acts as a potent pro-inflammatory cytokine on HUVEC and the activity is mainly mediated through the B-box of the protein. HMGB1 may be a key factor mediating part of the pro-inflammatory response occurring in septic shock and severe inflammation.     

葛花醒酒养胃颗粒对酒精性肝病内毒素损伤的防治作用

目的探讨葛花醒酒养胃颗粒对酒精性肝病(ALD)内毒素损伤的防治作用.方法Wistar大鼠48只随机分为正常组、模型组、葛花醒酒养胃颗粒治疗组(简称治疗组)和肝泰乐对照组(简称对照组).实验采用梯度酒精定量灌胃法制备酒精性肝病大鼠模型,造模同时治疗组予葛花醒酒养胃颗粒汤150mg·kg-1·d-1,分2次灌胃,对照组予肝泰乐水38mg·kg-1·d-1,分2次灌胃,正常组予同容积生理盐水,每日灌胃2次,连续灌胃8周后采血,检测大鼠血浆内毒素(LPS)、血清酶(ALT、AST、GGT)、血脂(Tch、TG)及血清肿瘤坏死因子(TNF-α)的含量,同时用RT-PCR法测定肝组织中脂多糖结合蛋白(LBP)和脂多糖受体CD14mRNA的表达.结果模型组大鼠血浆内毒素和血清TNF-α水平明显高于对照组(P＜0.05),肝组织中LBP和CD14mRNA的表达明显高于对照组(P＜0.05);同时血清ALT、AST、GGT、TG明显升高(P＜0.05);治疗组血浆内毒素和血清TNF-α水平明显低于模型组(P＜0.05),LBP和CD14mRNA的表达明显低于对照组(P＜0.05),血清ALT、AST、GGT、TG水平明显降低(P＜0.05).结论葛花醒酒养胃颗粒对大鼠酒精性肝损伤有较好的防治作用.     

Polymorphonuclear Leukocytes Released from the Bone Marrow Preferentially Sequester in Lung Microvessels

Objective : A hallmark of the systemic response to an inflammatory stimulus is the release of polymorphonuclear leukocytes (PMNs) from the bone marrow. This study was designed to measure the release of PMNs from the bone marrow and to determine their sequestration in the lung after an intravenous injection of either endotoxin (n = 5) or saline (n = 5). Methods and Results : The thymidine analogue 5′-bromo-2-deoxyuridine (BrdU) was used to pulse label dividing PMNs in the bone marrow of rabbits (n = 13), and immunohistochemistry and morphometry were used to detect the release of BrdU-labeled PMNs into the circulation and to determine their sequestration in the lung. Endotoxin treatment caused a drop in the circulating PMN counts (3.3 ± 0.08 at baseline to 0.12 ± 0.02 × 10⁹/L at 1 hour after endotoxin), which was followed by a neutrophilia at 8 hours (6.3 ± 1.1 × 10⁹/L, p < 0.01), an increase in circulating band cells (0.12 ± 0.01 at baseline to 2.18 ± 0.4 × 1⁹/L at 8 hours, p < 0.001), and an increase in the percentage of BrdU-labeled PMNs (0.01% ± 0.004% at baseline to 26.1% ± 3.2% at 8 hours, p < 0.001). Endotoxemia caused an arteriovenous difference in BrdU-labeled PMNs across the lung (35.9% ± 2.9% versus 26.1% ± 3.1%, mixed venous versus arterial, p < 0.02). Morphometric studies showed that endotoxin caused sequestration of PMNs in the lung (2.2 ± 0.4 versus 1.0 ± 0.2 × 10¹⁰, endotoxin versus saline, p < 0.03) with preferential retention of BrdU-labeled PMNs (0.79 ± 0.21 versus 0.039 ± 0.016 × 10¹⁰, endotoxin versus saline, p < 0.05). The percentage of BrdU-labeled PMNs in the alveolocapillary walls was higher than in circulating blood (64.01% ± 4.3% versus 26.1% ± 3.2%, p < 0.01) in the endotoxin group. In vitro filtration of cells through 5-mm pore size filters showed that circulating BrdU-labeled PMNs, 8 hours after endotoxin, were preferentially retained in the filters (p < 0.01). Conclusions : We conclude that endotoxemia stimulates the bone marrow to release mature and immature PMNs. Compared to PMNs released from the bone marrow during normal turnover, these PMNs are less deformable and preferentially sequester in the lung microvessels.     

超纯水透析液对维持性血液透析病人贫血、血浆内毒素及炎症因子水平的影响

目的:探讨超纯水透析液对维持性血液透析病人贫血、血浆内毒素及炎症因子水平的影响。方法:选取2018年3月—2019年3月维持性血液透析病人86例为研究对象,根据随机数字表法将病人分为观察组与对照组各43例。对照组行常规血液透析治疗,观察组应用超纯水透析液行维持性血液透析治疗,治疗时间均为6个月,比较两组病人贫血情况、血浆内毒素及炎症因子水平。结果:干预后观察组病人血红蛋白(Hb)及红细胞比容(HCT)水平明显高于对照组(P<0.05),每周重组人促红细胞生成素用量少于对照组(P<0.05),血浆内毒素、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)含量低于对照组(P<0.05)。结论:应用超纯水透析液行血液透析治疗能有效降低病人血浆内毒素及炎症因子水平,能明显纠正透析病人贫血,提高病人血液透析效果。     

感染根管细菌内毒素的致病机制与清除策略

细菌内毒素会影响牙髓根尖周疾病的发生发展及其治疗的预后。探究细菌内毒素的致病机制及清除措施对提高根管治疗的成功率及获得远期良好预后均有重要意义。本文就根管内细菌内毒素的产生、分布、致病机制以及清除策略等方面作一综述,为临床及基础研究提供新依据和新思路。     

胃肠道手术患者氧化应激反应对胃肠道功能恢复、切口愈合的影响及相关机制

目的探讨胃肠道手术患者氧化应激反应对胃肠道功能恢复、切口愈合的影响及相关机制。方法选取2018年8月至2019年8月在广西中医药大学第一附属医院外科行胃肠道手术的患者137例为手术组,另选取73例健康体检者为对照组。检测两组血清活性氧自由基(ROS)、D-乳酸、内毒素水平。比较手术组术前与对照组,以及术后不同胃肠道功能评分和切口愈合分级患者的血清ROS、D-乳酸、内毒素水平。分析血清ROS水平与D-乳酸和内毒素水平的相关性。结果手术组术前血清ROS、D-乳酸和内毒素水平均高于对照组,差异均有统计学意义(P<0.05)。随着胃肠道功能评分的增加,患者血清ROS、D-乳酸和内毒素水平逐渐升高,差异均有统计学意义(P<0.05)。与甲级切口愈合患者比较,乙、丙级切口愈合患者的血清ROS、D-乳酸、内毒素水平明显升高,差异均有统计学意义(P<0.05);与乙级切口愈合患者比较,丙级切口愈合患者的血清ROS、D-乳酸、内毒素水平明显升高,差异均有统计学意义(P<0.05)。术后胃肠道功能评分1、2、3分及乙、丙级切口愈合患者的血清ROS水平与D-乳酸、内毒素水平均呈正相关(P<0.05)。结论胃肠道手术患者发生的氧化应激反应会延缓胃肠道功能恢复,影响手术切口愈合。     

酪酸梭菌对非酒精性脂肪性肝病的疗效及对肠屏障的影响

目的探讨酪酸梭菌对非酒精性脂肪性肝病(NAFLD)患者肠屏障的作用及其对NAFLD的疗效和作用机制。方法选择在该院消化科就诊的NAFLD患者100例纳入NAFLD组,另选取50例健康体检者纳入对照组,比较两组的肠屏障功能指标[血清内毒素、二胺氧化酶(DAO)和D-乳酸]。将NAFLD组患者按照随机数字表法又分为A组、B组,两组均予以常规低脂饮食+有氧运动+双环醇1粒tid po,A组在此基础上,予以酪酸梭菌2粒tid po。将NAFLD组根据丙氨酸氨基转移酶(ALT)值分为ALT升高组和ALT正常组,比较两组肠屏障功能障碍发生率及炎性反应指标[白细胞介素(IL)-6、肿瘤坏死因子-α(TNF-α)]水平。分别于给药1个月后复查患者肠屏障功能、血脂[三酰甘油(TG)、总胆固醇(TC)]、肝功能、炎性反应指标等,并对A组与B组患者以上指标进行比较。结果NAFLD组的血清内毒素、DAO、D-乳酸水平均高于对照组,差异有统计学意义(P<0.05)。ALT升高组的TNF-α、IL-6水平明显高于ALT正常组,差异有统计学意义(P<0.05)。用药后A组与B组内毒素、D-乳酸、DAO水平均较用药前下降,A组下降比B组更明显,差异有统计学意义(P<0.05)。用药后A组与B组IL-6、TNF-α、TG水平均较用药前下降,A组下降比B组更明显,差异有统计学意义(P<0.05)。A组的总有效率(86.0%)高于B组(70.0%),差异有统计学意义(P<0.05)。结论NAFLD患者存在肠屏障损伤,可能与炎性反应激活有关。联合酪酸梭菌治疗有助于改善NAFLD患者的肠屏障功能,降低血脂水平,提高疗效。