小鼠急性酒精性肝损伤模型的建立

目的:建立一次性暴饮小鼠急性酒精性肝损伤模型,并动态研究肝脏病理形态学、氧化应激因子、炎症因子的变化.方法:将48只ICR小鼠随机分成2组,空白对照组一次性给予等热量、等体积的糖水6 g/kg灌胃,模型组一次性给予50%乙醇(6 g/kg)体质量灌胃,分别于灌胃后1.5、3、6、12 h动态监测小鼠血清谷丙转氨酶(alanine aminotransferase,ALT)、甘油三酯(triglyceride,TG),肝组织匀浆丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(reduced glulathione hormone(GSH)、超氧化物歧化酶(superoxide dismutase,SOD),及肝组织白介素-1β(interleukin 1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达;肝组织HE染色、苏丹Ⅲ染色观察肝组织形态学、脂肪变性程度.结果:成功复制了一次性暴饮50%乙醇(6 g/kg)的小鼠急性肝损伤模型,小鼠无死亡,出现翻正反射消失、嗜睡等醉酒状态.模型组小鼠血清ALT、TG水平随时间逐渐升高,6 h达峰值,12 h略下降;肝匀浆GSH含量6 h降至最低;造模后1.5 h肝脏SOD含量下降最为显著,下降约24%;1.5 h肝脏MDA含量上升最为显著,上升至正常组的2.2倍;肝脏IL-1β、TNF-α水平升高,12 h达峰值;HE染色结果示,造模后12 h可见中央静脉及小叶间经脉周围出现肝细胞肿胀、水样变性等病理改变;苏丹Ⅲ染色结果显示随着造模时间延长肝脂肪变性程度加重.结论:此模型造模周期短、易复制、稳定性好,是研究急性酒精性肝损伤发病机制和筛选药物的理想模型.     

Resolution of acute lung injury and inflammation: a translational mouse model

Previous animal models of acute lung injury (ALI) are limited as they only reproduce part of the complex pathobiology of clinical ALI. Here we develop a translational mouse model of ALI, which not only reflects the major clinical and pathological features but also enables investigation into ALI resolution. Anaesthetised mice underwent orotracheal instillation of hydrochloric acid. During the immediate period after instillation, mice were carefully maintained with supplemental oxygen to avoid mortality. At specified time-points, lung injury was assessed by analysis of blood gases, respiratory mechanics, bronchoalveolar lavage fluid, alveolar fluid clearance and lung histology. Animals exhibited significant weight loss, decreased oxygenation, increased respiratory elastance and pulmonary inflammation (intra-alveolar leukocyte influx/cytokine levels and histological injury scores). Moreover, mice displayed alveolar-capillary barrier dysfunction/epithelial injury as reflected by increased alveolar protein, lung wet/dry weight ratio and soluble receptor for advanced glycation end-products, as well as reduced alveolar fluid clearance. These injury parameters peaked between days 1 and 3, followed by almost complete recovery over days 5-10. Histology showed evidence of fibrosis on day 10. The results indicate that this resolving model of acid aspiration represents a powerful experimental tool to investigate the injurious, inflammatory, fibrotic, and resolving and reparative processes of ALI.     

Coping styles in fibromyalgia: effect of co-morbid posttraumatic stress disorder

To analyze coping styles of fibromyalgia (FM) patients with specific emphasis on differences in coping styles between fibromyalgia patients with and without post traumatic stress disorder (PTSD). Seventy-seven consecutive patients (40 women and 37 men) who fulfilled ACR criteria for FM, and 48 healthy controls, completed questionnaires measuring prevalence and severity of PTSD symptoms, including the structured clinical interview for DSM-III-R—non-patient edition (SCID-NP) and the clinician administered PTSD scale (CAPS). Subjects were divided into two groups based on the presence or absence of PTSD symptoms. Subsequently, coping styles were measured using the Albert Einstein College of Medicine (AECOM) Coping Style Questionnaire. Student t tests were used to compare the means of quantitative variables, and proportions were compared by Chi square tests. Analysis of variance (ANOVA) was used to compare the scores of the FM patients with and without PTSD, as well as to estimate the effect of gender on psychiatric variables. FM patients exhibit significantly higher levels of suppression (P < 0.00001), help-seeking (P < 0.007), replacement (P < 0.003), substitution (P < 0.002), and reversal (P < 0.004) compared with healthy controls. FM patients with PTSD and without PTSD differed significantly only on the suppression subscale (P < 0.02). FM patients that have PTSD presented higher suppression scores compared to FM patients without PTSD. No significant difference was noted on scales of minimization, help-seeking, replacement, blame, substitution, mapping, and reversal. Our results have delineated coping patterns of FM patients, identifying suppression, help-seeking, replacement, substitution and replacement as strategies more common among these patients. We further identified suppression as the only coping style significantly more common among FM patients with co-morbid PTSD then among FM patients without such a diagnosis. Our results may serve to further characterize cognitive and behavioral aspects of FM patients and subsequently guide therapeutic interventions.     

Genetic dissection of the biotic stress response using a genome-scale gene network for rice

Rice is a staple food for one-half the world's population and a model for other monocotyledonous species. Thus, efficient approaches for identifying key genes controlling simple or complex traits in rice have important biological, agricultural, and economic consequences. Here, we report on the construction of RiceNet, an experimentally tested genome-scale gene network for a monocotyledonous species. Many different datasets, derived from five different organisms including plants, animals, yeast, and humans, were evaluated, and 24 of the most useful were integrated into a statistical framework that allowed for the prediction of functional linkages between pairs of genes. Genes could be linked to traits by using guilt-by-association, predicting gene attributes on the basis of network neighbors. We applied RiceNet to an important agronomic trait, the biotic stress response. Using network guilt-by-association followed by focused protein-protein interaction assays, we identified and validated, in planta, two positive regulators, LOC_Os01g70580 (now Regulator of XA21; ROX1) and LOC_Os02g21510 (ROX2), and one negative regulator, LOC_Os06g12530 (ROX3). These proteins control resistance mediated by rice XA21, a pattern recognition receptor. We also showed that RiceNet can accurately predict gene function in another major monocotyledonous crop species, maize. RiceNet thus enables the identification of genes regulating important crop traits, facilitating engineering of pathways critical to crop productivity.     

The protective effect of ticagrelor on renal function in a mouse model of sepsis-induced acute kidney injury

Platelets are traditionally considered to be essential components of primary hemostasis. Recent investigations have revealed that platelets can be activated in patients with sepsis and are implicated in the development of sepsis and sepsis-induced-acute kidney injury (SAKI). In the present study, ticagrelor was used to induce a mouse model of SAKI by cecal ligation and puncture. It was found that ticagrelor could inhibit platelet activity, decrease the levels of interleukin-1β and serum creatinine, reduce infiltration of neutrophils in renal tissue, and attenuate cell apoptosis in the kidney. The results suggested that ticagrelor could protect renal function by inhibiting inflammation, recruitment of neutrophils into the kidney, and cell apoptosis in renal tissue. Thus, the findings might provide new strategies for preventing SAKI.     

Role of neutrophils in a mouse model of halothane-induced liver injury

Drug-induced liver injury (DILI) is a major safety concern in drug development. Its prediction and prevention have been hindered by limited knowledge of the underlying mechanisms, in part the result of a lack of animal models. We developed a mouse model of halothane-induced liver injury and characterized the mechanisms accounting for tissue damage. Female and male Balb/c, DBA/1, and C57BL/6J mice were injected intraperitoneally with halothane. Serum levels of alanine aminotransferase and histology were evaluated to determine liver injury. Balb/c mice were found to be the most susceptible strain, followed by DBA/1, with no significant hepatotoxicity observed in C57BL/6J mice. Female Balb/c and DBA/1 mice developed more severe liver damage compared with their male counterparts. Bioactivation of halothane occurred similarly in all three strains based on detection of liver proteins adducted by the reactive metabolite. Mechanistic investigations revealed that hepatic message levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta); IL-6, and IL-8 were significantly higher in halothane-treated Balb/c mice compared to DBA/1 and C57BL/6J mice. Moreover, a higher number of neutrophils were recruited into the liver of Balb/c mice upon halothane treatment compared with DBA/1, with no obvious neutrophil infiltration detected in C57BL/6J mice. Neutrophil depletion experiments demonstrated a crucial role for these cells in the development of halothane-induced liver injury. The halothane-initiated hepatotoxicity and innate immune response-mediated escalation of tissue damage are consistent with events that occur in many cases of DILI. In conclusion, our model provides a platform for elucidating strain-based and gender-based susceptibility factors in DILI development.     

Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing pancreatitis

INTRODUCTIONAcute pancreatitis complicated by multiple organ dysfunctions is still a life-threatening disease[1,2], although the precise mechanism by which such local inflammation in the pancreas progresses to systemic illness is still unclear. Recently, …     

Ligustrazine alleviates acute lung injury in a rat model of acute necrotizing pancreatitis

Introduction Acute pancreatitis is often complicated by lung injury. However, its pathogenesis remains unclear. It is known that AP involves a complex array of mediators that can initiate and amplify the systemic inflammatory response. This can lead to the failure of distant organ systems, such as the lungs, heart and kidneys,[1-3] among which, pulmonary failure is the most common.[4-7] Recent studies have indicated that during the pathogenesis of acute necrotizing pancreatitis (ANP), chang…     

大鼠急性肠道损伤动物模型的建立

目的:用三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)复制大鼠急性肠道损伤的动物模型.方法:SD大鼠64只随机分为制模组、制模对照组及正常对照组,分别用TNBS(乙醇稀释)、500 mL/L乙醇及生理水灌肠;观察各组大鼠制模后的粪便、精神状态、进食及存活情况;分别在第1、3、5、7及10天处死大鼠,取结肠组织,进一步观察肠道的大体病理变化和组织病理变化;再结合病理评分,总结大鼠TNBS制模后肠道病理改变的规律,评价该模型用于实验性肠道损伤研究的可行性.结果:TNBS制模组在制模后第1天即表现出明显的肠道稀便和血便,持续至实验结束;进食减少、懒动、畏寒,持续7-10 d后缓解;4只在制模后第7-9天死亡(4/34);制模后第1天即出现肠道病理改变,第5天出现急性肠道损伤,第7天病理改变最严重.制模对照组大鼠在制模后第1天部分出现稀便,持续1-2 d后消失;制模后第1天肠道出现轻度病理改变,3 d后病变减退;正常对照组大鼠未见异常,各组大鼠肠道病理评分与病变程度一致.结论:大鼠TNBS制模后早期即表现出肠道损伤,制模后第7天病理改变达到高峰,此后向慢性炎症转化:TNBS制模后5 d内可用于急性肠道损伤的实验性研究.     

The impact of posttraumatic stress disorder on upper gastrointestinal investigations in Australian Defence Force veterans: a retrospective review

Veterans with posttraumatic stress disorder (PTSD) commonly exhibit associated gastrointestinal (GI) symptoms. We compared upper GI endoscopy and abdominal ultrasound rates in veterans with and without PTSD. Veterans with PTSD were 77–81% more likely to undergo these procedures than those without PTSD. PTSD symptomatology influences GI investigation rate and more emphasis on clinician and patient education is recommended regarding stress-related gut symptoms.     

The effect of pre-existing alcohol use disorder on the risk of developing posttraumatic stress disorder: results from a longitudinal national representative sample

ABSTRACT

Background: There is inconsistent evidence in the literature as to whether or not Alcohol Use Disorder (AUD) is a risk factor for Post-Traumatic Stress Disorder (PTSD).

Objectives: We evaluated the risk of developing PTSD after trauma exposure in individuals with AUD. As a secondary analysis, we also tested if alcohol dependence or alcohol abuse separately increased the risk of PTSD development. We also explored the effect of AUD on exposure to various traumas.

Methods: Longitudinal data was obtained from 30,180 individuals with and without AUD from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) waves I and II. Using propensity score methods, we matched individuals with AUD (alcohol abuse and/or dependence using DSM-IV criteria) to those without AUD at baseline on demographic, familial, and clinical factors to estimate the risk of PTSD development after trauma exposure. Data were adjusted for complex survey methods.

Results: Individuals with AUD had an increased risk of being exposed to various traumas between wave I and II (60.6% vs. 48.3% of controls). Among individuals exposed to trauma between the two waves (N = 14,107), AUD had no effect on subsequent PTSD development after matching and controlling for covariates (OR: 1.00; 95%CI: 0.72–1.39; p = .99). However, those with alcohol dependence only did have an effect on subsequent PTSD development (OR: 1.76; 95%CI: 1.05–2.95; p = .03).

Conclusion: In individuals with alcohol dependence the experience of trauma increases the risk of developing PTSD. These findings suggest that prevention methods from PTSD after trauma exposure for individuals with alcohol dependence are needed.