妊娠期糖尿病孕妇血清脂肪因子Chemerin及白介素-6的表达

目的 探讨血清脂肪因子Chemerin及白介素-6(IL-6)与妊娠期糖尿病发生、发展的关系及相互作用.方法 选取2014年6月-2015年6月济宁医学院附属医院50例正常孕妇(正常组)及50例妊娠期糖尿病(GDM)孕妇(GDM组),采用酶联免疫吸附法(ELISA)检测终止妊娠前母体外周血中Chemerin及IL-6水平,行组间分析,分析其与临床相关特征的关系.结果 ①GDM组Chemerin的表达明显高于正常对照组,差异有统计学意义(p＜0.01);GDM组IL-6的表达高于正常对照组,差异有统计学意义(P＜0.05).②相关性分析表明,GDM组血Chemerin水平与IL-6呈显著正相关(r =0.756,P＜0.01).结论 GDM患者血清Chemerin及IL-6水平升高,可能参与了妊娠期糖尿病孕妇糖代谢紊乱,且IL-6对Chemerin的分泌可能具有一定的调节作用.

雷公藤内酯醇对内毒素激活小鼠腹腔巨噬细胞分泌促炎症介质NO和IL-6的影响

Objective Tripterygium wilfordii Hook. f. has been used for centuries in traditional Chinese medicine to treat autoimmune disease associated with increased production of the pro-inflammatory cytokine. Triptolide( TP) is a compound originally purified from T. wilfordii Hook f. and it has potent anti- inflammatory and immunosuppressant activities. In this study, we investigated the effect of TP on secretion of NO and IL-6 in celiac macrophages ( MΦ) activated by lipopolysaccharide ( LPS) in Kunming mice. Methods Celiac MΦ of mice were separated, purified, and activated by LPS, then cultured in vitro with TP of different concentrations. The level of NO in cellular supematants was determined by Griess reagent, and that of IL-6 was determined by ELISA. Results We found that pro-inflammatory cytokine NO activity in MΦ induced by LPS was significantly inhibited by TP ( 10-3-10 μg/ml) from 4-24 h in a time and dose- dependent manner (P < 0. 01). The level of IL-6 in MΦ was significantly inhibited by TP (10-3-10 μg/ml) at 12 h in a dose-dependent manner (P <0. 01). Conclusions We demonstrated that TP can inhibit levels of NO and IL-6 in celiac MΦ of Kunming mice activated by LPS.

Amentoflavone is a natural biflavone compound with many biological properties, including anti-inlfammatory, antioxidative, and neuroprotective effects. We presumed that amentolfavone exerts a neuroprotective effect in epilepsy models. Prior to model establishment, mice were intragastrically administered 25 mg/kg amentoflavone for 3 consecutive days. Amentoflavone effectively prevented pilocarpine-induced epilepsy in a mouse kindling model, suppressed nu-clear factor-κB activation and expression, inhibited excessive discharge of hippocampal neurons resulting in a reduction in epileptic seizures, shortened attack time, and diminished loss and apoptosis of hippocampal neurons. Results suggested that amentolfavone protected hippocampal neurons in epilepsy micevia anti-inlfammation, antioxidation, and antiapoptosis, and then ef-fectively prevented the occurrence of seizures.

孕激素在子痫前期患者TLR4-MyD88依赖的信号通路中的作用

目的 研究孕激素在子痫前期(preeclampsia,PE)孕妇Toll样受体4(toll-like receptor4,TLR4)-髓样细胞分化蛋白88(myeloid differentiation factor 88,MyD88)依赖的信号通路中的作用.方法 原代培养子痫前期孕妇外周血单个核细胞(peripheral blood mononuclear cell,PBMC),以不同浓度孕激素(0 mol/L、10-8 mol/L、10-6mol/L、 10-4mol/L)处理,实时定量聚合酶联反应(Real-time polymerase Chain reaction,real-time PCR)检测TLR4 mRNA、MyD88 mRNA、核转录因子-κB (nuclear factor κB,NF-κB) mRNA的表达;免疫印迹法Western blot检测IκB-α蛋白的表达,用凝胶图像处理系统分析各条目标带灰度值酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)检测细胞上清液中肿瘤坏死因子-α (tumor necrosis factors,TNF-α)及白介素-6(interleukin-6,IL-6)的表达.结果 随着孕酮浓度的增加,各组TLR4 mRNA、MyD88 mRNA及NF-κB mRNA的相对表达量2-△△Ct均逐渐降低,IκB-α蛋白的表达逐渐增加,差异均有统计学意义(均P<0.05);同时,细胞上清液中细胞因子TNF-α及IL-6的表达均逐渐减少,差异均有统计学意义(P<0.05).结论 孕激素可显著抑制TLR4-MyD88依赖的信号传导通路,对子痫前期患者具有保护作用.

目的：探讨血清中白细胞介素-6(IL-6)水平与宫内节育器(IUD)存在的关系。方法：采用酶联免疫吸附试验测定64例置器妇女(试验组，试验组又分为置器出血组和无出血组)，以及60例健康妇女(对照组)血清中IL-6水平，同时测定两组血清中C-反应蛋白(CRP)水平。结果：试验组64例中有31例血中IL-6水平升高，与对照组相比差异显著(P＜0．001)。但其中置器出血组与不出血组中IL-6水平无统计学差异(P＞0．05)。试验组及对照组血清中CRP检验结果均为阴性。结论：宫内节育器引起子宫内膜无菌性炎症反应，导致部分妇女血清中IL-6水平升高。IL-6可能在宫内节育器的避孕机理中起重要作用。

Objective :To develop an agent that is more active against receptor-bearing target cells without increasing the toxic effect on non-target cells. Methods :By the use of molecular biology techniques,we designed and constructed a fusion protein 5＇IL6-TNF△ by connecting the human interleukin-6 (hIL-6) gene and a human tumor necrosis factor α derivative (TNF△) gene througha synthetic linker sequence followed by subsequent expression in E. Coli. Results: In cytotoxicity assay with myeloma cell line U266, the normal type of 5＇ IL6-TNF△ showed an antitumor activity 3 times higher than that of TNF△;and the antitumor activity of 5＇IL6-TNF△ blocked by IL-6Rwas only 1/30 of that of normal type of 5＇ IL6-TNF△. Meanwhile,the 5＇IL6-TNF△ blocked by an ti-TNF antibody did not show any cytotoxicity to U266 cells. In activity assay with L929 cells ,the toxic effect of the fusion protein was found 1/22 of that of TNF△. Conclusion: The 5＇IL6-TNF△fusion protein might be a useful cytotoxic agent in cancer treatment.

精子脂质过氧化反应与致炎细胞因子

Aim:To investigate if interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-gamma (IFN-γ) or tumor necrosis factor-alpha (TNF-α) are able to stimulate the level of lipid peroxidation of sperm membranes, either alone or in the presence of leukocytes. Methods: Semen samples from normozoospermic donors were prepared by density gradient. The sperms were exposed to the indicated cytokines, at physiological and infection-inflammation concentrations, in the absence or presence of leukocytes. Lipid peroxidation of the sperm membranes was determined by measuring malondialdehyde (MDA) and 4-hydroxialkenals (HAE) formation. Results: TNF-α, IL-8 and IFN-γ increased the level of sperm membrane lipid peroxidation when tested at physiological concentrations. At infectioninflammation concentrations, only IL-8 was able to produce a higher effect. When assayed in the presence of leucocytes,IL-8 and TNF-α showed a higher effect at infection-inflammation concentrations than at physiological concentrations.Finally, IL-8 showed a higher effect in the presence of leukocytes than in their absence at both physiological and infection-inflammation concentrations. TNF-α also showed a higher effect when assayed in the presence of leukocytes than in their absence, but only at infection-inflammation concentrations. There was no effect of IL-6 or IL- 10 in any of the tested conditions. Conclusion: Several pro-inflammatory cytokines at physiological concentrations increase the level of lipid peroxidation of sperm membranes, which could be important for the sperm fecundation process. However, infection-inflammation concentrations of some cytokines, such as IL-8 and TNF-α, either alone or in the presence of leukocytes, could drive the lipid peroxidation of the spermatozoa plasma membrane to levels that can affect the sperm fertility capacity.

Objective:To investigate the effect of IL-6 gene transfer into human cord blood hematopoietic stem cells on the production of megakaryocytic progenitors. Methods: IL-6 gene was transfected into human cord blood CD34 + cells using a retrovirus vector with the aid of recombinant fibronectin fragments in the presence of a cocktail of cytokines (SCF, IL-6, sIL-6R, FL, and TPO). Colony-forming units-megakaryocyte (CFU-MK) assays were perfonned as IL-6 gene transduced CD34 + cells were incubated alone or in combination with IL-3 or sIL-6R, controlled with neoR gene transduced CD34 + cells. Results: IL-6 alone or sIL-6R alone stimulated few CFU-MK colonies, the addition of sIL-6R to IL-6 gene transduced CD34 + cells significantly enhanced the production of CFU-MK colonies. IL-6 gene transduced CD34 + cells showed a modest synergistic effect with IL-3. Conclusion: These results suggest that IL-6 gene transfer may protect patients from chemotherapy-induced thrombocytopenia.

let-7/miR-98家族对IL-6的调节作用

目的 探索微小RNA对IL-6的调节作用.方法 通过生物信息学预测发现let-7/miR-98家族可以调控IL-6基因,采用聚合酶链反应(RT-PCR)和酶联免疫法检测其对IL-6基因表达的影响,采用定点突变和双荧光报告基因系统来验证let-7/miR-98家族对IL-6基因的直接调节作用.结果 miR-98可以抑制IL-6蛋白的表达,miR-98对IL-6 mRNA也有抑制作用,let-7/miR-98可直接调节IL-6基因3'UTR.结论 let-7/miR-98家族可以直接调节IL-6基因的表达,提示let-7/miR-98家族可能成为干预IL-6参与的相关疾病的一种新药物.