Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus

BackgroundIncreasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats.MethodsWe examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins.ResultsOur study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones.ConclusionOur study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.     

Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.     

Toll-like receptor 3 dynamics in female C57BL/6J mice: Regulation of alcohol intake

Although there are sex differences in the effects of alcohol on immune responses, it is unclear if sex differences in immune response can influence drinking behavior. Activation of toll-like receptor 3 (TLR3) by polyinosinic:polycytidylic acid (poly(I:C)) produced a rapid proinflammatory response in males that increased alcohol intake over time (Warden et al., 2019). Poly(I:C) produced a delayed and prolonged innate immune response in females. We hypothesized that the timecourse of innate immune activation could regulate drinking behavior in females. Therefore, we chose to test the effect of two time points in the innate immune activation timecourse on every-other-day two-bottle-choice drinking: (1) peak activation; (2) descending limb of activation. Poly(I:C) reduced ethanol consumption when alcohol access occurred during peak activation. Poly(I:C) did not change ethanol consumption when alcohol access occurred on the descending limb of activation. Decreased levels of MyD88-dependent pathway correlated with decreased alcohol intake and increased levels of TRIF-dependent pathway correlated with increased alcohol intake in females. To validate the effects of poly(I:C) were mediated through MyD88, we tested female mice lacking Myd88. Poly(I:C) did not change alcohol intake in Myd88 knockouts, indicating that poly(I:C)-induced changes in alcohol intake are dependent on MyD88 in females. We next determined if the innate immune timecourse also regulated drinking behavior in males. Poly(I:C) reduced ethanol consumption in males when alcohol was presented at peak activation. Therefore, the timecourse of innate immune activation regulates drinking behavior and sex-specific dynamics of innate immune response must be considered when designing therapeutics to treat excessive drinking.     

不同浓度罗哌卡因复合舒芬太尼分娩镇痛对产妇产间发热的影响

目的研究不同浓度罗哌卡因复合舒芬太尼硬膜外注射用于分娩镇痛对产妇产间发热及致热因子的影响。方法适合阴道分娩、自愿要求分娩镇痛的初产妇120例,孕37～41周,年龄20～35岁,ASA I或Ⅱ级,随机分为三组:0.075%罗哌卡因组(A组)、0.1%罗哌卡因组(B组)和0.125%罗哌卡因组(C组),每组40例。宫口扩张至3 cm时实施硬膜外分娩镇痛,A组0.075%罗哌卡因+舒芬太尼0.5μg/ml;B组0.1%罗哌卡因+舒芬太尼0.5μg/ml;C组0.125%罗哌卡因+舒芬太尼0.5μg/ml。记录镇痛后1、2、3、4和5 h、胎儿娩出即刻、分娩后2 h产妇鼓膜温度;分别在镇痛前、胎儿娩出即刻及分娩后2 h采集产妇静脉血,测定血清IL-1β、IL-6、TNF-α浓度;记录产程时间;采用改良Bromage法评定三组产妇在镇痛后1 h及胎儿娩出即刻的运动神经阻滞程度。结果与镇痛前比较,镇痛后5 h及胎儿娩出即刻三组鼓膜温度明显升高,C组发热率明显高于A组和B组(P0.05)。与镇痛前比较,胎儿娩出即刻三组血清IL-1β、IL-6、TNF-α浓度明显升高(P0.05)。C组第二产程和镇痛时间明显长于A组和B组,B组第二产程和镇痛时间明显长于A组(P0.05)。三组运动神经阻滞程度差异无统计学意义。结论不同浓度罗哌卡因复合舒芬太尼硬膜外注射用于分娩镇痛均能产生良好的镇痛效果,低浓度罗哌卡因分娩镇痛产妇发热率低,产妇分娩期间发热与致热因子水平升高相关。     

Peritoneal dialysis improves lung function in rats with lung injury induced by shock wave

Objective To prove the efficacy of peritoneal dialysis on shock wave-induced acute lung injury of rats, and analyze its mechanisms. Methods Forty-five adult Sprague-Dawley rats were randomly divided into three groups: control group, sham operation (Sham) group and peritoneal dialysis (PD) group. Sham group and PD group did abdominal catheterization before blast injury. The 55 kg shock wave (bst-I) was used to induce lung blast injury. After one hour of blast injury, PD group was given 2.5% peritoneal dialysate 20 ml to stay abdomen, which was released 30 min posted, repeated 12 cycles. After 6 hours of peritoneal dialysis, all of the rats were sacrificed. Partial damaged tissues in lung were used to evaluate the pathomorphologic changes by HE staining, and the remnants were used to measure the lung water content. Lung function was detected by blood gas analyzer and small animal detector from the arterial blood gas. The levels of serum inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) were tested by ELISA. Results The relative integrity of alveolar structure, interstitial edema and inflammatory cell infiltration in PD group were significantly improved than those in control group. The lung water content of PD group was significantly lower than that of control group (P＜0.05). The levels of TNF-α, IL-1β, IL-6 and MCP-1 in serum of PD group were significantly lower than those in control group (all P＜0.05). The blood oxygen saturation, oxygen partial pressure, oxygenation index, vital capacity, functional residual volume and maximum mid-expiratory flow rate in PD group were significantly higher than those in control group (all P＜0.05). Conclusions Through reducing pulmonary edema and inflammatory factors, peritoneal dialysis can improve lung function in shock wave -induced acute lung injury of rats.     

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

BACKGROUND Acute pancreatitis(AP) is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs. Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity. Polyethylene glycols(PEGs) are nonimmunogenic, non-toxic water-soluble polymers widely used in biological, chemical, clinical and pharmaceutical settings.AIM To evaluate the protective effect of a 35-k Da molecular weight PEG(PEG35) on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.METHODS Wistar rats were assigned at random to a control group, a cerulein–induced AP group and a PEG35 treatment group. AP was induced by five hourly intraperitoneal injections of cerulein(50 μg/kg/bw), while the control animals received saline solution. PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42 J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α(TNFα), staurosporine or cerulein. The severity of AP wasdetermined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42 J-treated cells. Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage.RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats. The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas. In contrast, pancreatic tissue m RNA expression of interleukin 10 was markedly increased. PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats. Furthermore, the activation of pro-inflammatory markers and inflammationinduced cell death in pancreatic acinar cells treated with TNFα, cerulein or staurosporine was significantly reduced by PEG35 treatment, in a dose-dependent manner.CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42 J-treated cells through the attenuation of the inflammatory response and associated cell death. PEG35 may be a valuable option in the management of AP.     

会阴侧切切口感染危险因素及对患者Th1/Th2细胞因子水平的影响

目的探究会阴侧切切口感染危险因素及对患者Th1/Th2细胞因子水平的影响。方法从2018年1月-2019年1月于乳山市人民医院足月分娩行会阴侧切的产妇中随机抽样150例作为研究对象,根据是否继发切口感染,分为感染组52例和未感染组98例;制定调查表格,收集患者的临床资料,分析感染影响因素。所有受检对象均抽取外周静脉血3 ml,采用流式细胞分选技术(fluorescence-activated cell sorting,FACS)检测Th1、Th2细胞水平,计算Th1/Th2比值,采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)法检测γ-干扰素(Interferon-γ,IFN-γ)、白细胞介素-4(interleukin 4,IL-4)水平,计算两者比值。结果单因素分析显示:体质量指数、产程、妊娠期糖尿病、贫血、羊水污染及感染前住院时间是产妇会阴侧切术后切口感染的影响因素(P<0.05);多因素回归显示:体质量指数≥25 kg/m^2、产程≥8 h、合并妊娠期糖尿病、贫血、羊水污染及感染前住院时间≥72 h是产妇会阴侧切术后切口感染的危险因素(P<0.05);感染组的Th1细胞(15.29±4.52)、Th2细胞(7.13±2.89)高于非感染组,而Th1/Th2比值(2.47±0.86)低于非感染组(P<0.05);感染组的血清IFN-γ(31.46±4.19)pg/ml、IL-4(23.42±2.87)pg/ml高于非感染组,而IFN-γ/IL-4(1.25±0.13)低于非感染组(P<0.05)。结论产妇会阴侧切术后切口感染的影响因素较多,应采取针对性的干预措施,降低感染发生率。侧切切口感染产妇体内存在Th细胞亚群失衡现象,炎症因子水平紊乱。