褪黑素对内毒素血症山羊肝细胞线粒体呼吸功能的影响

将48只健康山羊随机分为4组：对照组（A组）、内毒素（LPS）组（B组）、内毒素＋褪黑素（LPS＋MT）组（C组）、褪黑素（MT）组（D组）,在处理后第3 h和6 h提取肝细胞线粒体,采用Clark氧电极技术测定线粒体呼吸控制率（RCR）、磷氧比值（P/O）、氧化磷酸化效率（OPR）的变化,探讨了MT对LPS诱导的山羊内毒素血症机体线粒体呼吸功能的影响。结果显示,内毒素组山羊在第3 h和6 h的RCR、P/O、OPR显著低于对照组（P〈0.05）;应用褪黑素后,即内毒素＋褪黑素组第3 h的肝细胞线粒体RCR、P/O、OPR明显升高（P〈0.05）;褪黑素组第3 h的RCR明显高于对照组（P〈0.05）,而褪黑素组第3 h的P/O、OPR与对照组差异不显著（P〉0.05）。证实,山羊内毒素血症时线粒体的呼吸功能明显下降,褪黑素对肝细胞线粒体呼吸功能具有一定的保护作用。     

Expression of tissue factor in experimental bovine pneumonic pasteurellosis and endotoxemia

Tissue factor (TF), a cell surface-associated cofactor and activator of coagulation factor VII, has been implicated in the local and systemic activation of coagulation associated with sepsis. This study describes the pattern of TF expression in experimental bovine pneumonic pasteurellosis and endotoxemia. Immunohistochemical techniques were used to localize TF antigen in tissue sections. Tissue factor expression was not observed in tissues from control animals. In response to Pasteurella haemolytica challenge, TF was expressed within alveolar walls, by mononuclear inflammatory cells within alveoli, and in walls of arteries, arterioles, bronchi, and bronchioles. Tissue factor was not detected in unaffected lung, liver, spleen, lymph node or kidney tissue. Administration of Escherichia coli endotoxin intravenously resulted in tissue factor expression in lung, spleen, and lymph node tissue. Results of this study indicate that TF is expressed locally at sites of inflammation and systemically in endotoxemia. Therefore, TF may be involved in coagulation events associated with pneumonic pasteurellosis.     

Effects of glycine on insulin resistance and cognitive impairment induced by high-fructose diet

AIM: To investigate the role of intestinal endotoxemia (IETM) in insulin resistance (IR) and cognitive impairment, and to explore the protective mechanisms of glycine in rats with high-fructose diet. METHODS: The rats in model group were fed with 8% fructose water, and the rats in intervention group were fed with water containing 8% fructose and 1% glycine. The body weight and systolic pressure were measured monthly. After 8 months, plasma glucose, plasma lipids, glucose tolerance and plasma endotoxin (LPS) were detected. Plasma insulin, pro-inflammatory cytokines in plasma and cerebral cortex were determined by ELISA, and HOMA-IR was also calculated. The molecules of insulin signaling pathway in cerebral cortex were determined by Western blotting. The cognitive functions of the rats were tested by Morris water maze. RESULTS: The weight gain in model group was increased from the 3rd month to the 6th month, and systolic pressure was increased after the 3rd month as compared with control group. Glycine significantly reduced the weight gain in the 4th month and the 6th month, and significantly reduced the systolic pressure from the 4th month to the 6th month. Meanwhile, glycine partly attenuated dyslipidemia and glucose intolerance, and lowered the levels of plasma LPS, plasma insulin, HOMA-IR and pro-inflammatory cytokines in plasma and cortex. Furthermore, glycine attenuated the abnormal expression of insulin signaling proteins and cognitive impairment. CONCLUSION: Long-term fructose diet induces the rats to peripheral and neuronal IR, which accompanies IETM and low-grade inflammation. Glycine attenuates IR and cognitive impairment by lowering IETM.     

卫气营血阶段性与内毒素血症兔不同时相 症状、体征的相关性研究

〔摘要〕目的观察内毒素血症兔不同时相的症状、体征动态变化,探讨其与卫气营血阶段性辨证及传变的相似 性〔方法将22只新西兰大耳白兔随机分成空白组8只和模型组14只,采用静脉注射大肠杆菌内毒素(LPS)的方法 建立内毒素血症模型,空白组注入等量无菌生理盐水,观察内毒素血症兔不同时相症状和体征动态变化,不同阶段 发热净增值的平均值(4T)〔结果(1)1阶段(注入大肠杆菌内毒素2 h),模型兔出现耸毛、发抖、喷嚏、流涕等症状〔 心率略增快,发热净增值(4T)比空白组升高,差异有统计学意义(P< 0.01)〔 (2)2阶段(攻毒后2-6 h),模型兔小便 黄、呼吸明显增快增粗、心率增快,耳廓发热、充血明显以及结膜充血,4T比前一阶段升高,差异有统计学意义(尸< 0.01)〔 (3)3阶段(攻毒后6-36 h),模型兔精神萎靡,活动度和灵敏度h降,出现便血、耳廓发凉、结膜充血明显,II 周青紫、耳廓青紫或有疲点疲斑、眼球突出、鼻哑 ,嗜睡、全身瘫软无力、角弓反张、抽搐和死亡,4T比前一阶段降 低,高于空白组,差异有统计学意义(P < 0.01)〔结论内毒素血症兔的症状、体征出现有规律性的阶段性表现,1阶段 (攻毒后2 h)与温病卫分证相关,2阶段(攻毒后2-6 h)与气分证相关,3阶段攻毒后6-36 h与营、血分证相关〔     

基于“肝脾理论”探讨肠源性内毒素血症致继发性肝损伤

运用中医肝脾理论相关内容剖析肠源性内毒素血症致继发性肝损伤的发生机制及其治疗思路,并从该角度阐述中西医理论内在联系,认为与肠源性内毒素血症致继发性肝损伤相联系,肠道黏膜屏障功能（intestinal barrier function,IBF）、胆汁酸的肠肝循环、肝与肠道免疫功能相互依赖、IBF障碍与肝损伤的恶性循环、改善肠道功能以保护肝脏的治疗理念均是肝脾理论现代生物学基础的具体体现。     

内毒素对山羊红细胞膜Na~+-K~+-ATP酶活力的影响

为了观察在发生内毒素血症时,山羊红细胞膜上Na+-K+-ATP酶活性以及红细胞内和血清中K+离子浓度的变化,将体重10 kg±1 kg的12只山羊,随机分为内毒素处理组(LPS,1 mg/kg)和生理盐水对照组。每组分别在处理后第0,0.5,1,2,3,4,5小时和第6小时从颈静脉采取血液样品。采血之后,制备红细胞、红细胞膜和血清。检测红细胞膜上Na+-K+-ATP酶活力,红细胞内和血清中K+浓度。结果表明,发生内毒素血症时,红细胞膜上Na+-K+-ATP酶活力和红细胞内K+离子浓度都先升高后降低,血清中K+离子浓度先降低后升高。     

Effects of intravenous administration of peripheral blood‐derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses

BackgroundA systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood‐derived mesenchymal stromal cells (PB‐MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB‐MSC administered IV to horses is well‐tolerated but therapeutic benefits are unknown.HypothesisAfter IV lipopolysaccharide (LPS) infusion, horses treated with PB‐MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo.AnimalsSixteen horses were included in this study.MethodsA randomized placebo‐controlled experimental trial was performed. Sixteen healthy horses were assigned to 1 of 2 treatment groups (1 × 10⁹ PB‐MSC or saline placebo). Treatments were administered 30 minutes after completion of LPS infusion of approximately 30 ng/kg. Clinical signs, clinicopathological variables, inflammatory cytokine gene expression, and oxidative stress markers were assessed at various time points over a 24‐hour period.ResultsA predictable response to IV LPS infusion was observed in all horses. At the dose administered, there was no significant effect of PB‐MSC on clinical signs, clinicopathological variables, or inflammatory cytokine gene expression at any time point. Antioxidant potential was not different between treatment groups, but intracellular ROS increased over time in the placebo group. Other variables that changed over time were likely due to effects of IV LPS infusion.Conclusions and Clinical ImportanceAdministration of allogeneic PB‐MSC did not cause clinically detectable adverse effects in healthy horses. The dose of PB‐MSC used here is unlikely to exert a beneficial effect in endotoxemic horses.     

Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep

The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the , AUC_0–∞, Cl_T, and V_dss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr⁻¹ kg⁻¹, and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the Cl_T of marbofloxacin decreased, AUC_0–∞ increased, and and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 µg/ml for E. coli, 0.016 to >16 µg/ml for M. haemolytica, 0.016–1 µg/ml for P. multocida, 0.016–0.25 µg/ml for K. pneumoniae, 0.031–0.063 µg/ml for Salmonella spp., and 0.031–1 µg/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.