共激活分子及相关因子对机体抗肿瘤免疫的调节作用

肿瘤在生长过程中,由于细胞转化产生的基因毒性应激和微环境的破坏,可激活具有抗肿瘤能力的效应细胞刺激专职抗原提呈细胞,触发T细胞和B细胞的特异性免疫反应。机体尽管存在免疫监视机制,但肿瘤的存在提示了瘤细胞逃避免疫反应的能力，其中包括各种逃避免疫识别的策略，例如表达死亡配体排除病灶的免疫细胞，通过降低主要组织相容性复合物（MHC）或共激活分子削弱免疫原性，以及干扰自然杀伤细胞（NK）和NKT细胞的识别能力。尽管面临诸如此类的问题，现代免疫治疗在治疗恶性疾病方面仍然显示出发展的前景。

低氧运动对营养性肥胖大鼠骨骼肌PGC-1α及其下游因子的影响

探讨低氧运动对营养性肥胖大鼠骨骼肌PGC-1α及其下游因子的影响。构建7周高脂膳食诱导SD大鼠营养性肥胖模型,建模后随机分为常氧高脂膳食安静组(NHQ)、常氧高脂膳食运动组(NHE)、16.3%低氧高脂膳食安静组(HGQ1)、16.3%低氧高脂膳食运动组(HGE1)、13.3%低氧高脂膳食安静组(HGQ2)、13.3%低氧高脂膳食运动组(HGE2),每组各10只。运动组进行8周耐力训练,即20 m/min、40 min/d,5 d/周。末次运动24 h后处死大鼠并采样,测定血脂4项和血糖(BG),q RT-PCR技术检测PGC-1α及其下游因子的表达(CPT-1、MCAD、PPARγ)。结果显示:1)7周高脂膳食可成功诱导营养性肥胖大鼠模型建立;2)与NHQ和HGQ1组相比,HGE1、HGE2和NHE组体质量下降非常显著或显著(P<0.01或P<0.05);与NHE组相比,HGE1和HGE2组体质量显著性下降(P<0.05);3)与NHQ组相比,NHE组MCAD m RNA表达非常显著性上调(P<0.01);HGE1组PGC-1α、MCAD、PPARγm RNA表达非常显著性增加或显著性增加(P<0.01或P<0.05);HGQ2组PGC-1αm RNA表达非常显著性上调(P<0.01);HGE2组PGC-1α、MCAD、CPT-1、PPARγm RNA表达非常显著性上调或显著性上调(P<0.01或P<0.05)。与NHE组相比,HGE1和HGQ2组PGC-1αm RNA表达显著性增加(P<0.05);HGE2组PGC-1α、MCAD、CPT-1、PPARγm RNA表达非常显著性上调或显著性上调(P<0.01或P<0.05);NHQ、HGQ1和HGQ2组MCAD m RNA表达非常显著性下降或显著性下降(P<0.01或P<0.05)。与HGQ1组相比,HGE1和HGQ2组PGC-1α、MCAD表达非常显著性上调或显著性上调(P<0.01或(P<0.05);HGE2组PGC-1α、MCAD、CPT-1 m RNA表达非常显著性上调(P<0.01);NHE组MCAD、PPARγm RNA表达非常显著性或显著性增加(P<0.01或P<0.05)。结果表明:(1)长期高脂膳食可诱导营养性肥胖发生。(2)低氧和(或)耐力运动可有效控制营养性肥胖大鼠体质量,增加骨骼肌PGC-1α及其下游基因的表达,13.3%低氧浓度下耐力运动效果较佳。

CD40-CD40L与疾病

T淋巴细胞与抗原提呈细胞之间的信号传递调控着免疫系统的发展 ,其中CD4 0与其配体CD4 0L(CD154)的相互作用 ,不仅对T细胞活化和效应功能的表现起重要作用 ,且在抗感染、抗病毒及抗肿瘤和动脉粥样硬化症中扮演重要角色。本文综述了CD4 0 -CD4 0L与人类疾病关系的研究进展。

应用RNA干扰技术阻断LNCap细胞SRC-1基因的表达及意义

目的：利用RNA干扰（RNA i）技术,阻断前列腺癌LNCap细胞中类固醇受体共激活分子（SRC-1）的表达,并研究SRC-1基因沉默后对LNCap细胞的影响。方法：将设计好的siRNA,用脂质体法转染LNCap细胞,通过Q-PCR、蛋白免疫印迹检测SRC-1的表达变化,并用CCK-8法检测细胞生长情况的变化。结果：转染SRC-1siRNA 24 h后的前列腺癌LNCap细胞中SRC-1 mRNA的量与空白对照组相比较下降了约35%,转染48 h后下降了约77%,差异具有统计学意义（P〈0.05）。转染24~48 h后LNCap细胞中SRC-1蛋白的表达量（24 h为0.359±0.034;48 h为0.257±0.065）与阴性对照组（24 h为0.782±0.078;48 h为0.766±0.043）、转染试剂组（24 h为0.840±0.013;48 h为0.786±0.051）和空白对照组（24 h为0.816±0.065;48 h为0.805±0.107）相比较明显减少（P〈0.05）。转染24、48、72、96 h后LNCap细胞的生长抑制率分别为25%、52%、55%和60%。结论：SRC-1与LNCap细胞的生长相关。SRC-1在激素非依赖性前列腺癌中的高表达可能参与了前列腺癌雄激素非依赖性的转变过程。抑制SRC-1的表达可能成为临床治疗激素依赖性前列腺癌的方法之一。

Study on the relationship between relieving energy crisis in myofascial trigger points with An-Pressing manipulation and AMPK/PGC-1α pathway activation

Objective To explore the mechanism of An-Pressing manipulation in relieving energy crisis in chronic myofascial trigger points(MTrPs)by observing the effects of An-Pressing manipulation on adenosine triphosphate(ATP),adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)/peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α)pathway and mitochondrial ultrastructure of skeletal muscle cells in MTrPs rats.Methods Forty-eight male Sprague-Dawley rats were randomly divided into a blank group,a model group,a lidocaine group,and an An-Pressing manipulation group,with 12 rats in each group.The model group,lidocaine group and An-Pressing manipulation group were used to replicate the MTrPs rat model by blunt shock and centrifugal motion method.After modeling,the An-Pressing manipulation group was subjected to 7 times An-Pressing manipulation,once every other day;the lidocaine group was treated with 3 times of injection of lidocaine at the MTrPs,once every 6 d.The blank group and the model group were fed normally without intervention.After the intervention,local muscle tissue was taken to detect the content of ATP and the expression of AMPK,phosphorylated AMPK(phospho-AMPK),PGC-1α,and glucose transporter 4(GluT4),and the ultrastructure of mitochondria was observed under an electron microscope.Results Compared with the blank group,the ATP content in the model group was decreased(P<0.05),the protein expression levels of phospho-AMPK,PGC-1α,and GluT4 and the ratio of phospho-AMPK to AMPK were decreased(P<0.05);under the electron microscope,the number of mitochondria decreased,and they were deformed,small in volume,and had deformed cristae.Compared with the model group,the ATP contents in the An-Pressing manipulation group and the lidocaine group were increased(P<0.05),and the protein expression levels of phospho-AMPK,PGC-1α,and GluT4 and the ratio of phospho-AMPK to AMPK were increased(P<0.05);under the electron microscope,the number of mitochondria increased,the shape and size of the mitochondria were basically normal,and the cristae could be seen.Compared with the lidocaine group,phospho-AMPK and the ratio of phospho-AMPK to AMPK in the An-Pressing manipulation group were increased(P<0.05);under the electron microscope,the numbers of mitochondria were similar,and the shape and size of the mitochondria were basically normal without swelling,and the cristae could be observed.Conclusion An-Pressing manipulation can increase the ATP content in MTrPs tissue,improve the expression levels of PGC-1α and GluT4 proteins and the ratio of phospho-AMPK to AMPK;its mechanism may relate to the activation of AMPK/PGC-1α signaling pathway to promote the repair of mitochondrial damages.