不同强度电针对肥胖大鼠细胞因子信号转导抑制蛋白-3及过氧化物酶体增殖物激活受体-γ mRNA表达的影响

目的:观察不同电针强度对单纯性肥胖大鼠脂肪组织中细胞因子信号转导抑制蛋白-3(SOCS-3),以及过氧化物酶体增殖物激活受体-γ(PPAR-γ)mRNA表达的影响,探讨电针对细胞信号传导通路的调控机制。方法:SD大鼠随机分为普食组、模型组、5mA电针组、1mA电针组,每组10只,喂食高脂饲料造肥胖大鼠模型。电针组针刺双侧"足三里"三阴交",每天治疗1次,每次15min,共治疗2周。观察大鼠治疗前后体质量变化情况,反转录-聚合酶链反应法检测大鼠附睾脂肪组织SOCS-3及PPAR-γmRNA的表达。结果:造模后,各组大鼠体质量及SOCS-3、PPAR-γmRNA表达较普食组均明显升高(P<0.01);治疗后,两电针组体质量及SOCS-3、PPAR-γmRNA表达较模型组均降低(P<0.01),5mA电针较1mA电针效果更明显(P<0.01)。结论:电针"足三里"三阴交"穴对单纯性肥胖大鼠体质量及SOCS-3、PPAR-γ过度表达有良性调节作用,5mA电针比1mA电针效果更好。     

细胞因子在糖尿病视网膜病变中作用的研究进展

糖尿病视网膜病变(diabetic retinopathy,DR)确切的发病机制尚不清楚.有研究认为,细胞因子可增加单核细胞和内皮细胞黏附的过程,进而引起视网膜毛细血管炎症反应,是DR发生发展的关键因素.本文就多种细胞因子,如血管内皮生长因子、肿瘤坏死因子、碱性成纤维细胞生长因子、色素上皮衍生因子等在DR中的作用进行综述.     

疏风解毒胶囊治疗肺炎配伍合理性及其机制研究

目的 对疏风解毒胶囊进行拆方研究,研究清热解毒组分、解表组分及其配伍组合分别对急性肺炎模型大鼠血清细胞因子水平的影响,从而分析疏风解毒胶囊配伍合理性。方法 制备肺炎链球菌致肺炎大鼠模型,分为对照组、模型组、头孢氨苄组、疏风解毒胶囊全方组（全方组）、疏风解毒胶囊解表组（解表组）、疏风解毒胶囊清热解毒组（清热解毒组）,连续给药6 d,检测各组大鼠血清中白细胞介素-1α（IL-1α）、IL-1β、IL-2、IL-4、IL-6、IL-10、肿瘤坏死因子-α（TNF-α）、α干扰素（IFN-α）、IFN-γ水平,评价组方配伍的合理性。结果 疏风解毒胶囊全方、解表组分、清热解毒组分均能显著降低IL-1α、IL-1β、IL-2、IL-4、IL-10水平,全方组大鼠在IL-1β水平上Q值>1;疏风解毒胶囊全方、解表组分、清热解毒组分均能显著降低TNF-α、IFN-γ水平,疏风解毒胶囊全方、解表组分能显著降低IFN-α水平;全方组大鼠在TNF-α、IFN-α水平这2个指标上Q值>1。结论 疏风解毒胶囊有显著的调节免疫功能的作用,解表组分和清热解毒组分有显著的协同作用。     

颈背肌切断复制家兔颈椎病模型颈椎间盘IL-1β、TNF-α含量变化的实验研究

目的通过对家兔颈椎病模型的建立,了解颈椎间盘IL-1β、TNF-α含量的变化及基因治疗对家兔退变椎间盘内细胞因子含量变化的影响。方法选用25只4个月龄新西兰兔,体质量2~3 kg,雌雄不分。随机分为正常对照组、模型浅层组、模型全层组、基因治疗浅层组、基因治疗全层组。建立家兔颈椎动力平衡失调模型,诱导颈椎间盘退变(正常对照组不做处理)。术后7个月,基因治疗组则将带有转化生长因子β1(TGF-β1)基因的重组质粒DNA注入C2—5椎间盘中(每个椎间盘用量为20μL)。8个月后用双抗夹心ELISA法检测各组动物颈椎间盘中IL-1β、TNF-α含量。结果模型组与正常对照组比较,颈椎间盘中IL-1β、TNF-α含量均明显升高(P均<0.01);基因治疗组与模型组比较,IL-1β、TNF-α含量明显降低(P均<0.05)。结论基因治疗能对退变颈椎间盘组织释放的多种细胞因子和炎性递质起明显的抑制作用。     

Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat

Abstract   Tumor necrosis factor alpha (TNF) injected into the sciatic nerve and neutralizing antibodies to its receptor injected around the nerve are respectively associated with inducing and blocking pain behavior beginning 1 to 3 days post-injection. This study examined the acute effects of TNF applied around the nerve trunk on the mechanical threshold (determined with von Frey hairs) and withdrawal latency to radiant heat. TNF (0.9 and 7.7 ng in 90 μL) injected onto the nerve via an indwelling catheter elicited a decrease in mechanical threshold. Following the low dose of TNF, no change in thermal latency was observed; after the 7.7 ng dose, thermal thresholds decreased and returned to baseline multiple times within the 3-hour observation period. Identical doses of TNF injected near, but not on the nerve, 90 ng of TNF injected on the nerve, and vehicle were without effect on either modality. These data indicate that effects of acutely administered TNF to the nerve trunk are capable of producing modality specific pain behavior. These changes may represent a first step in TNF-induced neuropathic pain.     

诱导痰及呼出气一氧化氮检查在支气管扩张症患者中的应用价值

背景　支气管扩张症（简称支扩症）是常见的气道慢性炎症性疾病,但患者存在明显异质性。诱导痰及呼出气一氧化氮（FeNO）检查已广泛应用于哮喘及慢性阻塞性肺疾病的病情评估,但是否有助于评估支扩症患者的气道炎症状态尚缺乏相关临床研究。目的　评估诱导痰及FeNO检查与支扩症患者临床特征、肺功能指标的关系,探讨无创气道炎症检查在支扩症患者中的应用价值。方法　选择2017年1月-2018年12月于沧州市中心医院就诊的稳定期支扩症患者62例为研究对象,记录患者性别、年龄、体质指数（BMI）、吸烟史、病程、急性加重次数、痰量、咯血史、发生支扩症的病因、铜绿假单胞菌定植等情况,并进行胸部高分辨率CT（HRCT）检查,记录HRCT评分;进行肺功能检查,记录第1秒用力呼气末容积占预计值的百分比（FEV1%pred）、用力肺活量占预计值的百分比（FVC%pred）、第1秒用力呼气末容积占用力肺活量的百分比（FEV1/FVC）、应用支气管扩张剂后第1秒用力呼气末容积（FEV1）增加量;进行诱导痰检查,测定白介素（IL）-8、IL-6、IL-13水平,观察细胞分型情况;进行FeNO检查,并记录FeNO。采用Pearson相关性分析探讨诱导痰检查的部分指标与FeNO及肺检查指标的相关性。结果　支扩症患者按照诱导痰细胞学分类可以分为中性粒细胞型（32例）、嗜酸粒细胞型（10例）、混合细胞型（6例）、寡细胞型（14例）。中性粒细胞型患者IL-8、IL-6水平高于嗜酸粒细胞型、寡细胞型患者,IL-13水平、FeNO、应用支气管扩张剂后FEV1增加量低于嗜酸粒细胞型、混合细胞型患者,HRCT评分高于嗜酸粒细胞型、混合细胞型、寡细胞型患者（P<0.05）;嗜酸粒细胞型患者IL-8、IL-6水平低于混合细胞型患者,IL-13水平、FeNO高于寡细胞型患者,应用支气管扩张剂后FEV1增加量高于混合细胞型、寡细胞型患者（P<0.05）;混合细胞型患者应用支气管扩张剂后FEV1增加量、IL-8水平、IL-6水平、IL-13水平、FeNO高于寡细胞型患者（P<0.05）。IL-8水平与HRCT评分（r=0.625）、中性粒细胞百分比（r=0.711）呈正相关,与FEV1%pred（r=-0.327）、FVC%pred（r=-0.401）、FEV1/FVC（r=-0.398）、应用支气管扩张剂后FEV1增加量（r=-0.312）呈负相关（P<0.05）;IL-6水平与HRCT评分（r=0.342）、中性粒细胞百分比（r=0.221）呈正相关（P<0.05）;IL-13水平与应用支气管扩张剂后FEV1增加量（r=0.439）、嗜酸粒细胞百分比（r=0.536）、FeNO（r=0.526）呈正相关（P<0.05）;中性粒细胞百分比与HRCT评分（r=0.548）呈正相关,与FEV1%pred（r=-0.372）、FVC%pred（r=-0.345）、FEV1/FVC（r=-0.253）、应用支气管扩张剂后FEV1增加量（r=-0.346）、嗜酸粒细胞百分比（r=-0.553）呈负相关（P<0.05）;嗜酸粒细胞百分比与应用支气管扩张剂后FEV1增加量（r=0.522）、FeNO（r=0.576）呈正相关（P<0.05）;FeNO与应用支气管扩张剂后FEV1增加量（r=0.423）呈正相关（P<0.05）。结论　诱导痰细胞分类、IL-8、IL-6、IL-13水平及FeNO与支扩症患者临床指标相关,有助于支扩症患者病情的综合评价。     

骨肉瘤分子发瘸学的研究进展

骨肉瘤是儿童及成人中最常见的原发性恶性骨肿瘤，进展迅速，早期即出现转移。近20年来，新辅助化疗／术后辅助化疗联合手术、放疗的应用使骨肉瘤患者的预后有了很大改善。但是那些伴有转移及复发的患者的预后依然较差。这需要进一步从分子生物学层面上认识其病因学。本文对近年来骨肉瘤病因学研究的进展作一阐述，以期为寻找新的治疗靶点提供方向。     

Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966

The formation of metastases in multiple organs and acquired multi-drug resistance (MDR) are the major obstacles for treatment of human small-cell lung cancer (SCLC). To explore the possibility of immunological overcoming of multiple-organ metastases produced by refractory SCLC, we established the MDR variant (SBC-3/DOX), expressing P-glycoprotein, of parental SBC-3 cells by culturing with gradually increasing concentration of adriamycin. Both SBC-3 and SBC-3/DOX cells expressed a high amount of ganglioside GM2, an ideal target of SCLC cells. A mouse-human chimeric anti-GM2 monoclonal antibody (KM966) induced antibody-dependent cellular cytotoxicity (ADCC) mediated by human mononuclear cells (lymphocytes and monocytes) and complement-dependent cytotoxicity (CDC) mediated by human AB serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells. Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype. These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological circumvention of multiple-organ metastases of refractory SCLC. This revised version was published online in July 2006 with corrections to the Cover Date.     

Tanshinone IIA Ameliorates Trinitrobenzene Sulfonic Acid (TNBS)-Induced Murine Colitis

Inflammatory bowel diseases are characterized by proinflammatory cytokines, oxidative stress, and tissue damage. Recently, tanshinone had been shown to act as an antioxidant, and to have anti-inflammatory bioactivity. The study was carried out to investigate the effect of tanshinone IIA on the inflammatory response of experimental colitis. Murine colitis was induced by trinitrobenzene sulfonic acid (TNBS). Ten or 20 mg tanshinone IIA was administrated to mice 4 h before the induction of colitis, and repeated daily until the mice were sacrificed. Colonic inflammation was examined by histological analysis, myeloperoxidase (MPO) activity, and the production of proinflammatory cytokines in colonic tissue. Activation of nuclear factor-kappa B was identified by western blot and immunohistochemistry, and oxidative stress was shown by glutathione (GSH) level in tissue. The mice with colitis treated by tanshinone IIA showed less tissue damage, lower MPO activity, less production of TNF-α and IL-1β, a higher level of GSH in colonic tissue, and downregulated activation of nuclear factor-kappa B in lamina propria mononuclear cells, compared with those of the untreated colitis group. Our data indicates that tanshinone IIA inhibits inflammatory response of colitis by downregulating the production of proinflammatory cytokines, and attenuating oxidative stress, which suggests that tanshinone IIA may be a new potential management for inflammatory bowel diseases.