胰腺癌细胞通过高表达核因子E2相关因子2促进巨噬细胞血管内皮生长因子表达的实验研究

目的:探讨胰腺癌细胞对巨噬细胞血管内皮生长因子(VEGF)表达的影响及核因子E2相关因子2(Nrf2)在其中的作用。方法:检测单一人胰腺癌细胞(PANC-1)培养组、单一巨噬细胞培养组、肿瘤细胞和巨噬细胞共培养组中各细胞VEGF表达。利用野生组、Nrf2过表达组、Nrf2敲减组中PANC-1的条件培养基刺激巨噬细胞,检...     

毛木耳多糖对小鼠腹腔巨噬细胞蛋白激酶A活性的影响

目的：观察毛木耳多糖（APSP）体外对小鼠腹腔巨噬细胞（MΦ）蛋白激酶A（PKA）活性的影响。方法：采用反相离子对高效液相色谱法,测定MΦ中PKA活力。结果：毛木耳多糖（80mg.L^-1)能引起小鼠腹腔MΦA中PKA活性明显升高,8min表峰值,20min恢复到基础水平,8min毛木耳多糖与PKA活性担效关系具有一定的浓度依赖性。结论：毛木耳多糖的免疫增强作用与其增强MΦ中PKA活性有关。     

抗巨噬细胞移动抑制因子单抗对溃疡性结肠炎小鼠治疗效果及炎症因子水平的影响

目的 探讨抗巨噬细胞移动抑制因子(MIF)单抗对溃疡性结肠炎(UC)小鼠治疗效果及炎症因子水平的影响.方法 选取30只雄性BALB/c小鼠,分为正常对照组、UC模型组、抗MIF单抗组各10只,以5％葡聚糖硫酸钠诱导建立小鼠UC模型,建模后抗MIF单抗组采用抗MIF单抗腹腔注射给药.给药期间观察各组小鼠一般情况并进行疾病活动指数(DAI)评分、大肠大体损伤评分及组织学评分.建模后第8天检测血清MIF、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)浓度.结果 与正常对照组比较,UC模型组及抗MIF单抗组小鼠DAI评分、大肠大体损伤评分及组织学评分均明显增高(P＜0.05);与UC模型组比较,抗MIF单抗组DAI评分、大肠大体损伤评分及组织学评分均明显下降(P＜0.05);与正常对照组相比,UC模型组及抗MIF单抗组MIF、TNF-α和IL-6浓度显著升高(P＜0.05);与UC模型组相比,抗MIF单抗组MIF、TNF-α和IL-6浓度降低(P＜0.05).结论 抗MIF单抗能有效地抑制UC小鼠血清炎症因子的水平,对UC的治疗有一定的效果.     

靶向抑制巨噬细胞Act1表达对溃疡性结肠炎的作用

目的 探讨巨噬细胞NF-κB活化因子1（nuclear factor kappa B activator 1,Act1）在炎症性肠病中的作用。方法 以巨噬细胞Act1表达被靶向抑制的小鼠（anti-Act1）为研究对象,利用葡聚糖硫酸钠（dextran sodium sulfate,DSS）诱导溃疡性结肠炎模型,通过检测小鼠体重变化、便血情况、粪便黏稠度等进行疾病活动指数评分,对结直肠组织进行HE染色评价炎症严重程度,免疫组化方法分析白细胞和巨噬细胞等的浸润情况并用RT-qPCR法检测相关细胞因子的表达变化。结果 在DSS诱导7 d后与C57小鼠相比,anti-Act1小鼠结直肠炎症指标评分较低,巨噬细胞等浸润数量较少,TNF-α、IL-1β和IL-6 mRNA表达较低。结论 靶向抑制巨噬细胞Act1表达能够减轻DSS诱导的溃疡性结肠炎。     

Neutrophils infiltrating ultraviolet B-irradiated normal human skin display high IL-10 expression

Exposure to an erythemal dose of ultraviolet B (UVB) is known to induce interleukin (IL-10) expression in human skin. It is generally believed that this IL-10 is predominantly expressed by CD11b⁺HLA-DR⁺ macrophages that infiltrate the UVB-exposed skin. This cytokine is presumed to contribute to the immunosuppressive effects of UVB by inhibiting cell-mediated immune responses. We recently demonstrated that neutrophils, which also invade UVB-irradiated skin, express CD11b and HLA-DR as well. In addition, we showed that the presence of these neutrophils affects T-cell responses in primary T-cell cultures derived from UVB-exposed skin. Since neutrophils invade UVB-exposed skin and, like macrophages, express CD11b and HLA-DR, we sought to determine whether neutrophils represent another source of IL-10. Skin biopsies were obtained from four healthy volunteers before and 2 days after exposure to four minimal erythema doses of UVB. A series of immunohistochemical double-staining procedures using the following markers was performed: IL-10, CD11b, HLA-DR, CD36, neutrophil elastase, and CD66b. As expected IL-10 could be detected in CD11b⁺HLA-DR⁺CD36⁺ macrophages in the epidermis and dermis of UVB-exposed skin. Surprisingly, the majority of the abundant IL-10 expression was found in CD11b⁺HLA-DR⁺elastase⁺CD66b⁺ neutrophils. Cytospin preparations from dermal cell suspensions confirmed the IL-10 expression by neutrophils displaying characteristic multilobular nuclei. Thus, neutrophils in UVB-exposed skin express IL-10 and should be recognized as active coplayers in the creation of the UVB-induced immunosuppressive microenvironment.     

前列腺素E对氧化和糖基化低密度脂蛋白影响的比较研究

应用生物化学，组织化学和形态计量学等技术对低密度脂蛋白的氧化和糖基化损伤进行了比较研究，同时观察了前列腺素Ｅ类药物的影响。结果显示：与对照组相比，氧化低密度脂蛋白组的抗氧化酶活性明显低落，过氧化脂质含量显著升高，但前列腺素Ｅ类药物却明显提高抗氧化酶活性，抑制过氧化脂质生成。巨噬细胞含脂的形态计量学分析表明前列腺素Ｅ，尤以前列腺素Ｅ２明显抑制泡沫细胞形成。糖基化修饰低密度脂蛋白机理较为复杂，其两酶活     

橙皮素抗apoE-/-小鼠动脉粥样硬化作用及其机制

目的探讨橙皮素抗apoE-/-小鼠动脉粥样硬化作用及其机制。方法40只8周龄apoE-/-小鼠随机分为4组,即普通饮食组(NC)、动脉粥样硬化高脂饮食组(WD)、橙皮素高剂量(100 mg/kg)组(H-HES)、橙皮素低剂量(50 mg/kg)组(L-HES),各10只。采用灌胃方式给予橙皮素,根据每只小鼠体质量给予不同的剂量,12周后处死小鼠前眶静脉采血,全自动生化分析仪检测血清三酰甘油、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇浓度,并采用ELISA试剂盒检测apoE-/-小鼠血清中肿瘤坏死因子(TNF-α)和单核细胞趋化蛋白-1(MCP-1)的浓度,麻醉小鼠后左心室灌注多聚甲醛固定,主动脉树油红O染色观察斑块百分比,同时取材主动脉窦采用免疫荧光技术观察斑块巨噬细胞的浸润情况。结果与NC组比较,WD组、H-HES组及L-HES组apoE-/-小鼠血清TC、TG、LDL-C浓度显著升高,HDL-C显著降低(P<0.05),且H-HES及L-HES组TC、TG、LDL-C的水平显著低于WD组(P<0.05)。高脂高胆固醇饲料喂养12周后,WD组的主动脉树动脉粥样硬化病变非常显著,其主动脉树的AS斑块面积百分比为(0.1430±0.0604),而H-HES组、L-HES组的主动脉树AS的面积百分比分别为(0.0404±0.0175)、(0.0252±0.0195),与WD组相比,H-HES组、L-HES组主动脉树AS病变显著减轻,差异有统计学意义(P<0.05)。WD组的主动脉窦动脉粥样硬化斑块部位巨噬细胞浸润增加,经过橙皮素12周治疗后,H-HES和L-HES组主动脉窦斑块部位CD68巨噬细胞浸润减少(P<0.05)。WD组apoE-/-小鼠血清MCP-1和TNF-α的浓度分别为(807.33±122.46)、(9.87±1.75)μg/L高于H-HES及L-HES组的(365.83±66.31)、(6.34±0.65)μg/L及(405.74±46.21)、(9.48±0.82)μg/L,差异有统计学意义(P<0.05)。结论橙皮素有明显的调脂降血脂作用,同时具有抗动脉粥样硬化效果,其主要通过抗炎发挥药理作用。     

Effect of IgE-stimulated alveolar macrophages on tracheal epithelial bioelectric properties in dogs

To investigate a possible interaction between pulmonary alveolar macrophages (AMs) and airway epithelial cells in patients with allergic conditions, we studied the effect of AMs on bioelectric properties of canine tracheal epithelium under short-circuited conditions in vitro. Mucosal addition of the supernatants from AMs stimulated with monoclonal antidinitrophenyl (DNP) IgE antibody and DNP-human serum albumin (DNP-HSA) increased short-circuit current (Isc) of cultured epithelium in a dose-dependent manner. The maximal increase from the baseline value and the EC₅₀ were 10.2±2.0μA/cm² (mean ± SE, p<0.01) and 3×10⁵ AMs/ml, respectively. This effect was accompanied by the release of prostaglandin E₂ and F_2α from AMs. In contrast, AMs incubated with anti-DNP IgE antibody alone or DNP-HSA alone had no effect. The AM-induced increase in Isc was attenuated by diphenylamine-2-carboxylate and Cl-free medium but not by amiloride. Pretreatment of AMs with indomethacin or piroxicam inhibited the effect of AMs on epithelial Isc. These results suggest that AMs may stimulate Cl secretion across the airway mucosa through an IgE-dependent release of prostaglandins.