细胞间黏附分子-1在中枢神经系统疾病中的表达和调控

细胞间黏附分子-1(ICAM-1)分布于体内多种组织细胞表面,是具有广泛生物学活性的一种黏附因子,在炎症与免疫应答、信号转导、组织修复等多种生理与病理过程中起重要作用。现就ICAM-1在体内的表达与调控,以及其在某些中枢神经系统疾病发病中的作用作一综述。     

小分子IGF-1R抑制剂的研究进展

胰岛素样生长因子1受体(IGF-1R)的信号转导途径与肿瘤的发生密切相关。抑制IGF-1R的活性，可以有效控制肿瘤细胞的生长和转移，并增强肿瘤对化疗、放疗的敏感性。以IGF-1R为靶标的治疗方法中，IGF-1R单克隆抗体和小分子激酶抑制剂已进入临床试验阶段。本文对近年来以IGF-1R为靶点的小分子激酶抑制剂的研究进展进行综述。     

基于前药构建混合胶束实现紫杉醇/阿霉素共递送

为了达到靶向递送,实现肿瘤的联合治疗,制备两亲性紫杉醇-聚乙二醇前药以及小分子阿霉素前药,两者共同构成混合胶束实现共递送.合成还原敏感性的聚乙二醇-紫杉醇前体药物(mPEG-SS-PTX)和靶向性叶酸修饰的聚乙二醇-紫杉醇前体药物(FA-PEG-SS-PTX).同时合成pH敏感阿霉素-乌头酸酐(CAD)小分子前药,采用...     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

子宫内膜异位症患者子宫内膜HIF-1α、CD34、CD54的表达及相互关系

目的观察缺氧诱导因子1α(HIF-1α)、CD34、CD54与子宫内膜异位症(EMS)发生的关系,以期探讨EMS的发病机制。方法选取26例EMS手术患者,所有病例均经腹腔镜或开腹手术确诊,经病理证实为腹膜型EMS 8例,卵巢子宫内膜异位囊肿9例,子宫腺肌症9例,同期选取子宫肌瘤手术患者6例为对照组,应用免疫组织化学法(SP)测定2组子宫内膜组织中HIF-1α、CD34、CD54的表达。结果 HIF-1α、CD34、CD54在腹膜型EMS组、卵巢子宫内膜异位囊肿组、子宫腺肌症组的表达均高于对照组,差异有统计学意义(P0.05)。HIF-1α与CD34、CD54的表达呈正相关。结论 HIF-1α可能在EMS异位病灶形成中起重要作用,推测内异症的发生与局部病灶缺氧有关。且HIF-1α与CD34的表达呈正相关,提示HIF-1α可以促进内异症组织血管生成;HIF-1α与CD54的表达呈正相关,推测HIF-1α可加强异位内膜细胞的黏附作用,从而有利于形成异位灶。     

利用单克隆抗体特异性敲除技术解析中药药效物质基础的新方法

中药药效物质基础研究是实现中药现代化的关键问题之一。作者将小分子单克隆抗体技术引入中药药效物质基础研究,利用中药活性成分的单克隆抗体制备相应的免疫亲和色谱柱,实现从药材或复方中特异性地"敲除"该化合物,而"原样"保留其他成分在量和比例关系上不变,通过药理药效的比较研究,来明确揭示该成分与整体中药或复方功能主治的关联度。利用单克隆抗体特异性敲除技术解析中药药效物质基础,是符合中药自身特点的药效物质基础研究新方法,获得的研究结果不仅有助于从全新的角度理解物质基础,而且有助于理解中药单味药内部,或复方药味之间"配伍"的现代科学意义。     

Alteration of Leukocyte–Endothelial Cell Interaction During Aging in Retinal Microcirculation of Hypertensive Rats

Purpose Hypertension, one of the more common chronic diseases affecting the elderly, has been reported to influence leukocyte–endothelial cell interaction. The leukocyte-mediated inflammatory process contributes to age-related changes in vessels. This study was designed to evaluate age-related changes in leukocyte–endothelial cell interaction in the hypertensive rat retina. Methods Male spontaneous hypertensive rats (SHR; 1.5, 3, 6, 12, and 20 months of age) and age-matched Wistar-Kyoto rats (WKY) were used. The number of accumulated leukocytes was counted in sections of flat-mounted retinal tissue. The expression of intercellular adhesion molecule-1 (ICAM-1) and CD18 (the common β-chain of ICAM-1 ligands) was evaluated. Retinal thickness was evaluated histologically. Results The number of accumulated leukocytes and the expression of ICAM-1 and CD18 increased in the aged retina. The number of leukocytes that accumulated and the expression of CD 18 were significantly higher in the SHR group than in the WKY group (P < 0.01). In addition, retinal thickness decreased with age. Conclusion Leukocyte–endothelial cell interaction increased in the aged retina and these changes were more severe in SHR retina than in WKY retina. This increased interaction was first observed at 3 months, a relatively young age.     

131I治疗后Graves眼病血清TNF-α、sTNFRⅡ和sICAM-1的相关性研究

目的探讨G raves病眼病(GO)伴有甲状腺功能亢进症(甲亢)患者经131I治疗后,血清肿瘤坏死因子-α(TNF-α)、可溶性肿瘤坏死因子受体Ⅱ(sTNFRⅡ)和可溶性细胞间粘附分子-1(sICAM-1)的相关性。方法 131I治疗6～12个月间,根据"NOSPECS眼部病变分级"分为无GO组14例、轻度GO组35例和中度GO组35例,按"CAS评分"分为GO静止组32例和GO活动组38例。设对照组29例。采用ELISA方法检测各组患者血清sI-CAM-1、TNF-α和sTNFRⅡ水平。结果 GO活动组血清sICAM-1(1211.9±258.6ng/m l)水平高于对照组(697.8±291.0 ng/m l)、无GO组和GO静止组(797.6±250.0 ng/m l、807.9±330.2ng/m l,P<0.01),GO静止组和GO活动组血清TNF-α(378.1±167.9ng/L、391.6±150.7ng/L)水平均高于无GO组和对照组(P<0.01);无GO组、GO静止组和GO活动组血清sTNFRⅡ(730.0±173.3ng/L、1055.1±422.9 ng/L、960.0±435.4 ng/L)水平均高于对照组(P<0.01)。轻度GO组、中度GO组血清sICAM-1(1032.4±232.3 ng/m l、407.0±158.1 ng/L)和TNF-α(1021.9±448.9 ng/m l、375.2±157.8 ng/L)水平均高于无GO组和对照组(P<0.05);而无GO组、轻度GO组和中度GO组血清sTNFRⅡ(730.0±173.3 ng/m l、1154.4±422.9 ng/L、922.1±440.6 ng/L)水平均高于对照组(P<0.05)。全部患者血清sICAM-1分别与TNF-α、sTNFRⅡ呈正相关,(r=0.377,P=0.001,r=0.434,P=0.001),TNF-α和sTNFRⅡ之间呈正相关(r=0.476,P<0.001)。结论 GO患者131I治疗的早期,通过血清sICAM-1、TNF-α和sTNFRⅡ的表达对活动性突眼、眼眶内免疫炎性反应,纤维组织变化和甲亢缓解进行综合评价,并可结合CAS评分了解GO患者预后、甲状腺及眼眶的免疫学及细胞凋亡的状态,指导有针对性治疗。     

调脂通脉颗粒对ApoE基因敲除小鼠血脂及sICAM-1、sVCAM-1的影响

目的:探讨调脂通脉颗粒对载脂蛋白E(ApoE)基因敲除小鼠血脂、动脉粥样斑块及黏附分子的影响。方法:6周龄雄性ApoE-/-小鼠随机分为模型组、血脂康组、调脂通脉颗粒低中高剂量组,C57BL/6小鼠作为对照组,每组8只,高脂饮食结合药物喂养12周,血清检测观察血脂变化,主动脉弓根部石蜡切片苏木素伊红(HE)及马松(Masson)染色观察组织形态学变化,酶联免疫法(ELISA)检测血清可溶性细胞间黏附分子(sICAM-1)、可溶性血管细胞间黏附分子(sVCAM-1)表达。结果:血脂检测表明与正常对照组比较,调脂通脉颗粒各组、血脂康组、模型组小鼠血清总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平均显著升高(P<0.01),模型组、调脂通脉颗粒低剂量组小鼠血清甘油三酯(TG)水平明显升高(P<0.01);HE、Masson染色表明对照组主动脉内膜光滑未见粥样斑块形成;模型组主动脉内膜增厚伴易损斑块形成;血脂康组及调脂通脉颗粒高剂量组内膜增厚伴稳定斑块形成。ELISA法检测表明与正常组比较,调脂通脉颗粒各组、血脂康组、模型组小鼠血清sICAM-1、sVCAM-1水平显著升高(P<0.05),与模型组比较,调脂通脉颗粒高剂量组小鼠血清sICAM-1、sVCAM-1水平显著降低(P<0.05)。结论:调脂通脉颗粒可在一定程度上降低血清TG及sICAM-1、sVCAM-1水平,从而减缓AS病变。     

广西牡蛎小分子化合物的分离鉴定与抗肿瘤活性研究

目的提取分离广西钦州牡蛎中小分子物质,对结构进行鉴定,同时研究其对肿瘤细胞生长抑制的生物活性。方法通过匀浆、酶解、醇沉、透析等实验方法分离牡蛎多糖后,牡蛎匀浆上清液用醋酸乙酯萃取,醋酸乙酯提取浓缩液经硅胶柱反复分离纯化,得小分子物质,并利用IR,NMR、MS对其结构进行鉴定,另外通过MTT法观察各物质对鼻咽癌细胞(CNE-1)生长抑制作用。结果利用硅胶柱色谱技术,分离得A、B、C、D白色结晶,经重结晶和TLC比较,B、C、D晶体为单一物质,B为scalaradial,C、D两化合物分别为色氨酸和苯丙氨酸。MTT实验结果表明B晶体随着浓度的增大,对鼻咽癌细胞(CNE-1)抑制作用也增大,具有浓度依赖性,IC50为138μg/ml。A,C,D三种晶体对鼻咽癌细胞(CNE-1)生长抑制作用不明显。结论牡蛎中存在抑制肿瘤细胞生长作用的小分子化合物,有必要进一步系统开展对牡蛎活性成分的筛选研究。