白头翁汤对炎症性肠病中促炎细胞因子表达的影响

目的：探讨白头翁汤治疗炎症性肠病的分子机制。方法：40只Wistar雄性大鼠随机分为5组（n=8）：正常对照组、模型组、模型＋阳性药物对照组（美沙拉嗪）、模型＋白头翁中、高剂量治疗组。阳性对照组、中药治疗组分别灌胃给药。疗程结束后取大鼠结肠组织提取RNA,利用realtimePCR的方法检测白介素-1β（IL-1β）、白介素-6（IL-6）YL肿瘤坏死因子-α（TNF-α）在各组中的表达变化。结果：相对于模型组,阳性药物及白头翁汤治疗组尤其是高剂量组可有效抑制IL-1β、IL-6及TNF-α的表达。结论：白头翁汤可通过抑制促炎因子的表达从而发挥了在炎症性肠病中的治疗作用。     

Trim22对脂多糖诱导的巨噬样细胞促炎细胞因子的负向调节作用

目的: 构建人Trim22的重组逆转录病毒载体,观察过表达Trim22对脂多糖(LPS)诱导的巨噬样细胞促炎细胞因子产生的影响。方法: 经PCR法扩增,把Trim22克隆入逆转录病毒载体MSCV2.2 IRES-GFP(MSCV),并对重组载体进行菌落PCR、双酶切及测序鉴定。用Lipofectamine将MSCV、GAG-POL、VSV-G载体共转染至293T包装细胞。用病毒上清感染U937细胞,通过流式细胞仪分选GFP阳性细胞。用佛波酯诱导U937细胞分化为巨噬样细胞,LPS刺激后观察过表达Trim22对促炎细胞因子表达的影响。结果: 经测序等鉴定,成功构建MSCV-Trim22逆转录病毒表达载体。病毒上清感染U937细胞后,经流式细胞仪分选获得稳定表达Trim22的U937细胞。LPS刺激巨噬样细胞后,Trim22过表达组TNFα和IL6的表达水平显著小于对照组(P<0.05)。结论: 成功构建人Trim22的逆转录病毒表达载体,Trim22能抑制LPS诱导的巨噬样细胞TNFα和IL6的产生。     

抗炎合剂对脓毒症小鼠心肌损伤的保护作用及机制

摘要 目的：探讨抗炎合剂对脓毒症致心肌损伤的保护作用及可能机制。方法：将32只体重22～25 g的雄性C57小鼠随机分为4组：正常组、假手术组、模型组（脓毒症模型）、抗炎合剂组。采用盲肠结扎穿孔术（cecal ligation and puncture,CLP）建立脓毒症模型,模型组、抗炎合剂组在造模后分别用生理盐水、抗炎合剂（Anti-inflammation mixture,AIM）对大鼠进行干预。正常组：正常进食饮水;假手术组：假手术前每天给予生理盐水（1.4 mL/100 g）,并腹腔注射生理盐水（5 mg/kg）每日1次,连续3日。第4日行假手术;模型组（CLP组）：CLP术前给予生理盐水（1.4 mL/100 g）,每天1次,并腹腔注射生理盐水（5 mg/kg）每日1次,连续3日。第4日CLP;抗炎合剂组：CLP术前给予中药抗炎合剂（1.4 mL/100 g）,每天1次,并腹腔注射生理盐水（5 mg/kg）每日1次,连续3日。第4日行CLP;各组分别于手术后24小时行标本采集,采用HE染色和TUNEL染色观察小鼠心肌组织损伤情况,同时检测小鼠血清肿瘤坏死因子-α（TNF-α）和炎症因子白细胞介素-1β（IL-1β）水平。结果：与正常对照组或假手术组相比,CLP模型组小鼠的心肌组织出现大量炎性细胞浸润,心肌细胞凋亡率显著升高（P<0.01）;而抗炎合剂组相较于CLP模型组心肌细胞凋亡率显著下降（P<0.01）。与正常对照组或假手术组相比,CLP模型小鼠血清TNF-α、IL-1β水平显著升高（P<0.001）,而中药抗炎合剂组TNF-α、IL-1β水平相较于模型组显著降低（P<0.01）。此外,与正常对照组和假手术组相比,模型组SIRT1 mRNA水平和蛋白表达水平显著降低,抗炎合剂显著提高SIRT1的mRNA和蛋白表达水平。结论：抗炎合剂可能通过提高SIRT1的表达,抑制CLP脓毒症小鼠的炎症反应,进而减轻心肌损伤。     

舒芬太尼复合地佐辛镇痛对中老年胸科手术后胰岛素抵抗及促炎细胞因子的影响

目的:研究舒芬太尼复合地佐辛镇痛对中老年胸科手术后胰岛素抵抗及促炎细胞因子的影响。方法:选取2012年12月到2014年12月我院收治的中老年胸科手术患者80例,按照随机数字表法将患者分为研究组和对照组,每组40例。研究组给予舒芬太尼复合地佐辛镇痛,对照组给予舒芬太尼镇痛,比较两组术后2 h和24 h视觉模拟评分(VAS)和镇静程度评分(Ramsay),比较手术前、术后2 h和24 h两组胰岛素含量、胰岛素敏感性以及肿瘤坏死因子-a(TNF-a)、白介素-6(IL-6)情况。结果:术后2 h和24 h研究组VAS评分均显著低于对照组,Ramsay评分显著高于对照组,两组比较差异具有统计学意义(P0.05);两组术后2 h和24 h胰岛素含量、胰岛素敏感性比较差异具有统计学意义(P0.05);手术前两组TNF-a、IL-6水平比较均无统计学意义(P0.05),术后2 h和24 h研究组TNF-a、IL-6显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论:舒芬太尼复合地佐辛应用于中老年胸科手术具有较好的术后镇痛效果,且具有抑制胰岛素抵抗和促炎细胞因子的作用。     

甲炎康泰颗粒剂对自身免疫性甲状腺炎大鼠免疫相关细胞因子的影响

目的 检测甲炎康泰颗粒剂对自身免疫性甲状腺炎大鼠免疫相关细胞因子的影响,探讨甲炎康泰颗粒剂改善自身免疫性甲状腺炎的作用机制。方法 30只雌性Lewis大鼠随机选取正常组10只,其余20只采用皮下注射甲状腺球蛋白结合口服碘水造模共7周。造模成功大鼠随机分为模型组10只、给药组10只。甲炎康泰颗粒剂连续干预8周后,ELISA法检测甲状腺抗体水平;HE染色观察甲状腺病理改变;qPCR法检测靶点因子基因表达;抗体芯片法检测靶点蛋白表达并绘制聚类热图。结果 模型组TPOAb、TGAb较正常组显著升高,给药组TPOAb、TGAb较模型组显著降低。模型组甲状腺滤泡细胞破坏、大量淋巴细胞浸润,给药组甲状腺病理改变较模型组缓解。模型组IFN-γ、TNF-α、IL-17、CCL3、CX3CL1基因表达量较正常组升高,给药组IL-4、IFN-γ、TNF-α、IL-17、CCL3、CX3CL1较模型组降低。各组间细胞因子聚类较好,模型组IL-17、CCL3、CX3CL1蛋白表达量较正常组升高,给药组IL-4、IFN-γ、TNF-α、CCL3、CX3CL1较模型组降低。结论 甲炎康泰颗粒剂可调节免疫相关细胞因子...     

复合应激型ED大鼠模型促炎细胞因子IL-6、TNF-α和TGF-β1水平的研究

目的:探讨环境雌激素样饲料联合冷刺激诱导的ED大鼠血清与阴茎组织中促炎因子IL-6、TNF-α和TGF-β1的变化及其对ED大鼠阴茎组织纤维化的影响.方法:取100只SD雄性大鼠,20只为正常组(N),其余120只为建模组,以环境雌激素样饲料联合冷刺激予以复合干预,24周后通过APO阴茎勃起实验和交配实验筛选ED大鼠,...     

高压氧疗法对创伤性脑损伤大鼠氧化应激指标及促／抗炎细胞因子水平的影响

目的：研究高压氧（HBO）疗法对创伤性脑损伤（TBI）大鼠氧化应激指标及促／抗炎细胞因子水平的影响方法：SD雄性大鼠18只,随机分为3组（n=6）：假手术组、损伤对照组和HBO治疗组采用Feency法建立大鼠TBI模型,假手术组只开放骨面,不予打击HBO治疗组大鼠于脑损伤后6h采用动物高压舱,以3ATA压力纯氧治疗60min。所有动物于手术后24h处死,分离脑组织,取伤侧脑半球行组织匀浆,分别测定匀浆上清液中超氧化物歧化酶（SOD）、丙二醛（MDA）、NO的含量以及促炎细胞因子TNF-α、IL-6、IL-1β及抗炎细胞因子IL-10的水平,结果：与损伤对照组相比,HBO治疗使SOD、NO以及IL-10水平升高,同时降低脑内MDA及TNF-α、IL-6、IL-1β的含量结论：HBO治疗可抑制TBI后自由基的生成,从而减轻脂质过氧化反应;同时,HBO治疗可减少促炎细胞因子的生成,促进抗炎细胞因子的产生,从而可减轻损伤脑组织的炎症反应,有助于减轻TBI后脑组织的继发性损伤.     

脓毒症分子机制及miRNA在脓毒症中的作用

脓毒症是外科重症监护病房(ICU)的主要死亡原因。近年来其发病呈上升趋势,且住院费用极昂贵,并缺乏有效的救治手段,已成为重症医学研究的重点。目前,关于脓毒症的发病机制并不清楚。研究表明,细胞内及细胞间多种信号通路如核因子κB(NF-κB)通路、丝裂原激活的蛋白激酶(MAPK)通路、JAK激酶/信号转导和转录激活子(JAK/STAT)通路、磷脂酰肌醇3激酶(PI3K/Akt)通路、胆碱能抗炎通路等及其下游的分子都参与脓毒症的发生发展。微小RNA(miRNA)作为小分子非编码RNA,通过转录后水平抑制靶基因的表达而参与细胞的多种过程。miRNA可以调控免疫细胞的分化及免疫反应,其不仅可以直接调控炎症因子的表达,还可作用于炎症信号传导通路的其他关键分子而间接调控脓毒症的发生发展。因此深入研究miRNA在脓毒症中的调节作用,可能为脓毒症的预防和治疗开拓新的思路。本文就参与脓毒症的信号通路及其下游分子以及miRNA进行总结,以利于进一步阐明脓毒症的病理生理机制,为脓毒症的预防和治疗找到合理有效的切入点。     

脓毒症早期胰岛素强化治疗对血清促炎症因子/抗炎症因子水平的影响及疗效观察

目的探讨脓毒症早期胰岛素强化治疗对血清促炎症因子/抗炎症因子水平的影响及疗效观察。方法选取住院治疗的脓毒症患者64例,采用随机数字表将其分为研究组和对照组,每组32例。两组患者入院后立即予以抗感染、营养支持、维持水电解质酸碱平衡及治疗基础疾病等常规治疗。研究组在此治疗基础上按Hirsch推荐方法予以胰岛素持续泵入治疗,在24 h内使血糖维持在4.4~6.1 mmol/L;常规组患者在此治疗基础上予以常规使用胰岛素治疗,在24 h内使血糖维持在10.0~11.1 mmol/L。观察两组患者治疗前和治疗4 d后血清IL-1、IL-6和IL-10水平的变化,并比较其抗生素使用时间、住院时间、MODS发病率及病死率。结果治疗4 d后,两组患者血清IL-1和IL-6水平较前明显下降,血清IL-10水平较前明显上升(P0.01或P0.05),且研究组下降或上升值较常规组更明显(P0.05);同时研究组患者抗生素使用时间、住院时间和MODS发病率明显少于常规组(P0.05),两组患者的病死率比较差异无统计学意义(P0.05)。结论脓毒症患者早期胰岛素强化治疗的疗效明显优于传统的常规使用胰岛素治疗,能缩短抗生素使用时间和住院时间,降低MODS发病率,改善其预后,作用可能与其能降低血清促炎症因子IL-1和IL-6水平,提高抗炎症因子IL-10水平,纠正血清促炎症因子/抗炎症因子比例失调密切相关。     

取样方式对大鼠皮瓣缺血再灌注损伤模型细胞因子测定的影响

目标:利用大鼠腹岛状皮瓣构建缺血再灌注损伤模型,评价距血管夹闭点近、中、远不同距离的位置取样是否会影响细胞因子的检测,为该模型实验确立一种合理的取样方式。方法:对术后5天的大鼠成活皮瓣按照近、中、远三个位置进行取样,分别测定各样品的4种细胞因子IL-1β,IL-6,TNF-α和EPO的表达量,并用配对T检验分析评价三种取样方式。结果:样品中IL-1β,IL-6,TNF-α和EPO在缺血再灌注组的表达水平较假手术组显著上调;同一细胞因子在同一皮瓣不同取样位置的表达量在统计学上无显著性差异。结论:取样位置并不影响细胞因子的测定,即可以从成活皮瓣的任意位置取样测定相应细胞因子,但是在同一批实验中不同皮瓣取样位置须一致。     

胰岛素对糖尿病大鼠肝细胞氧化损伤的影响

利用四氧嘧啶建立糖尿病大鼠模型 ,研究了胰岛素对糖尿病大鼠肝细胞及线粒体氧化损伤的保护作用。结果表明 ,胰岛素 1U kg皮下注射 9d ,能明显降低肝组织谷丙转氨酶、谷草转氨酶、乳酸脱氢酶、黄嘌呤氧化酶的活性 ,显著提高肝组织丙二醛的含量及肝线粒体O· -2 (活性氧自由基 )的生成量 ,显著提高抗氧化酶谷胱甘肽过氧化物酶、超氧化物歧化酶的活性 ,提高肝线粒体H+ ATPase的合成活力 ,从而使受损的肝细胞功能得到改善     

银杏内酯B 对星形胶质细胞氧化损伤的保护作用

目的:探讨银杏内酯B对过氧化氢(H_2O_2)诱导的星形胶质细胞损伤的保护作用及可能机制。方法:星形胶质细胞传代培养,分为阴性对照组(以正常培养液培养),氧化损伤组(100μmol·L~(-1)的H_2O_2作用12 h),银杏内酯B低剂量组(1×10~(-6) mol·L~(-1)银杏内酯B孵育24 h后,加入H_2O_2作用12 h)和银杏内酯B高剂量组(1×10~(-4) mol·L~(-1)银杏内酯B孵育24 h后,加入H_2O_2作用12 h),MTT比色法检测细胞存活率,流式细胞仪检测细胞活性氧(ROS)水平,分光光度计检测上清液中超氧化物歧化酶(SOD)、如谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)的含量。结果:银杏内酯B能抑制氧化损伤引起的细胞活性的下降,降低星形胶质细胞内ROS的生成,促进SOD、GSH-Px水平的升高及MDA水平的下降。结论:银杏内酯B通过提高细胞内SOD、GSH-Px含量,降低细胞内MDA含量发挥其较强的抗氧化作用,从而为其用于治疗神经系统疾病提供可靠的实验依据。     

脓毒症患者血清氧化应激因子、炎症因子水平与APACHE Ⅱ评分及预后的关系研究

目的:探讨脓毒症患者血清氧化应激因子、炎症因子水平与急性生理学与慢性健康状况Ⅱ(APACHE Ⅱ)评分及预后的关系.方法:选择2016年1月-2019年10月我院收治的脓毒症患者76例作为研究组,同期收治的相同基础疾病非脓毒症患者60例作为对照组,比较两组血清氧化应激因子[丙二醛(MDA)、超氧化物歧化酶(SOD)、一...     

Protective Effects of Antioxidants Against Cadmium-induced Oxidative Damage in Rat Testes

The protective effects of melatonin, vitamin E, and selenium alone or in combination were tested against cadmium-induced oxidative damage in rat testes. A total of 60 male rats were equally divided into five study groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the fourth group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and the testes were excised for histological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of the enzyme (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to the nontreated animals (p < 0.05) and an increase in the superoxide dismutase activity that was almost the same as the controls. The combination of melatonin, vitamin E, and selenium appears to have the more profound effect against cadmium-induced testicular injury.     

Effects of Selenium with Vitamin E and Melatonin on Cadmium-Induced Oxidative Damage in Rat Liver and Kidneys

The present study was performed to determine the protective effects of melatonin alone and vitamin E with selenium combination against cadmium-induced oxidative damage in rat liver. A total of 60 male rats were equally divided into five groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the four group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and liver and kidneys were excised for histopathological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of superoxide dismutase (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to nontreated animals (p < 0.05) and increase in the enzyme activity that was almost the same as the controls. The pathological findings were also in parallel with the results of the biochemical analysis. In conclusion, all the agents tested had protective effects against cadmium-induced oxidative damage.     

低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响

Nrf2可调节多种抗氧化酶的表达,Nrf2的缺失可能影响机体的运动能力,而低氧可提高机体的抗氧化能力并改善运动能力。为了考察低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响,本研究分别在常氧和低氧环境(12%氧浓度)中对野生型大鼠和Nrf2敲除大鼠进行4周的跑台运动。研究显示,低氧运动可提高野生型大鼠的跑台运动力竭时间,Nrf2敲除可缩短大鼠的力竭时间;低氧运动可上调大鼠的Nrf2 m RNA表达量;Nrf2敲除明显抑制HIF-1α蛋白表达,而低氧运动可上调野生型和Nrf2敲除大鼠的HIF-1α蛋白表达;Nrf2敲除大鼠的骨骼肌ROS水平明显升高,并且低氧均可降低野生型和Nrf2敲除大鼠骨骼肌ROS水平。低氧运动可上调Nrf2敲除大鼠的CAT和GSH-PX蛋白表达。苏木精和伊红(HE)染色显示,Nrf2敲除大鼠在力竭跑台运动完成后出现更严重的骨骼肌病理改变,而低氧运动可减轻骨骼肌损伤。本研究认为,Nrf2敲除导致了大鼠骨骼肌中抗氧化酶的抑制及ROS的过量累积,从而造成了骨骼肌损伤并降低了运动能力。此外,低氧可通过上调Nrf2的表达,进而激活HIF-1α及抗氧化酶活性,从而提高运动能力,并防止骨骼肌损伤。     

Copper Intoxication; Antioxidant Defenses and Oxidative Damage in Rat Brain

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Even though Cu is essential to life, it can become toxic to cells, at elevated tissue concentrations. Oxidative damage due to Cu has been reported in recent studies in various tissues. In this study, we aimed to determine the effect of excess Cu on oxidative and anti-oxidative substances in brain tissue in a rat model. Sixteen male Wistar albino rats were divided into two groups: the control group, which was given normal tap water, and the experimental group, which received water containing Cu in a dose of 1 g/l. All rats were sacrificed at the end of 4 wk, under ether anesthesia. Cu concentration in the liver and in plasma alanine aminotransferase (ALT) and aspartate transaminase (AST) activities were determined. There were multiparameter changes with significant ALT and AST activity elevation and increased liver Cu concentration. In brain tissue, Cu concentration, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and glutathione (GSH) concentrations were determined. Brain Cu concentration was significantly higher in rats receiving excess Cu, compared with control rats (p < 0.05). Our results showed that SOD activities and GSH levels in brain tissue of the Cu-intoxicated animals were significantly lower than in the control group (p < 0.01 and p < 0,001, respectively). The brain MDA levels were found to be significantly higher in the experimental group than in the control group (p < 0.001). The present results indicate that excessive Cu accumulation in the brain depressed SOD activities and GSH levels and resulted in high MDA levels in brain homogenate due to the lipid peroxidation induced by the Cu overload.     

Repair of Oxidative DNA Damage in Saccharomyces cerevisiae

Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomolecules including DNA and consequently activates various DNA repair pathways. The nature of DNA damage and the cell cycle stage at which DNA damage occurs determine the appropriate repair pathway to rectify the damage. Oxidized DNA bases are primarily repaired by base excision repair and nucleotide incision repair. Nucleotide excision repair acts on lesions that distort DNA helix, mismatch repair on mispaired bases, and homologous recombination and non-homologous end joining on double stranded breaks. Post-replication repair that overcomes replication blocks caused by DNA damage also plays a crucial role in protecting the cell from the deleterious effects of oxidative DNA damage. Mitochondrial DNA is also prone to oxidative damage and is efficiently repaired by the cellular DNA repair machinery. In this review, we discuss the DNA repair pathways in relation to the nature of oxidative DNA damage in Saccharomyces cerevisiae.     

茶多酚对NASH 大鼠肝脏组织VEGF 及氧化应激的影响

目的:茶多酚对NASH大鼠肝脏组织VEGF及氧化应激的影响。方法:雄性SD大鼠30只,随机分为3组,正常对照组、模型组、茶多酚治疗组。正常组普通饲料喂养,模型组喂高脂饮食,茶多酚治疗组在高脂饮食12周后茶多酚(150mg(/kg.d)灌胃治疗,16周末处死各组大鼠,留取肝脏组织,观察各组大鼠肝组织病理改变,测定其肝脏丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及血管内皮生长因子(VEGF)、Ⅰ、Ⅲ型胶原的表达。结果:模型组大鼠肝组织中SOD活性降低而MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达均明显高于正常组。茶多酚治疗可减轻肝纤维化程度,显著升高肝组织中SOD活性、降低MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达水平。结论:茶多酚可通过抑制肝纤维化组织VEGF表达,降低肝组织氧化应激水平而发挥抗肝纤维化作用。     

Coexistence of Aflatoxicosis with Protein Malnutrition Worsens Hepatic Oxidative Damage in Rats

To investigate the effects of the coexistence of aflatoxin B1 (AFB1) and protein malnutrition in rat liver, weanling rats were fed either normal protein diet (20% protein), low‐protein (PEM) diet (5%), normal protein diet + 40 ppb AFB1, or low‐protein diet + 40 ppb AFB1. After 8 weeks, biomarkers of hepatic functions and oxidative stress, caspase‐3 activity, and tumor suppressor protein 53 (p53) were determined spectrophotometrically. Randomly amplified polymorphic DNA polymerase chain reaction (RAPD‐PCR) was employed to determine genomic alterations among the groups. Coexistence of aflatoxicosis and PEM significantly decreased glutathione, glutathione‐S‐transferase, glutathione peroxidase, and superoxide dismutase, while it increased peroxidase and catalase. RAPD‐PCR showed genomic alterations that were associated with significant increases in p53 level and caspase‐3 activity in rats fed PEM diet + AFB1. In conclusion, the coexistence of aflatoxicosis and protein malnutrition induced oxidative stress with concomitant genomic alterations in the liver of weanling rats.