MMPs与慢性子宫内膜炎及不孕症的研究

基质金属蛋白酶是一族依赖锌离子而降解各种细胞外基质的蛋白酶.基质金属蛋白酶的组织特异性抑制物是一组多功能基因家族,它们能特异性地抑制基质金属蛋白酶.基质金属蛋白酶-2和基质金属蛋白酶-9是最典型的代表,在子宫内膜均有表达.基质金属蛋白酶的组织特异性抑制物-1是基质金属蛋白酶-9的特异性抑制因子;基质金属蛋白酶的组织特异性抑制物-2是基质金属蛋白酶-2的天然抑制物.在胚胎植入等过程中,基质金属蛋白酶发挥着重要的作用.该文就基质金属蛋白酶-2和基质金属蛋白酶-9及其抑制物与慢性子宫内膜炎和不孕症的关系进行综述.     

均匀设计法优选祛斑凝胶剂基质处方

目的：优选祛斑凝胶剂基质处方。方法：采用U₆（6²×3）均匀设计法,以凝胶剂的流变学参数（在室温下的黏度和屈服值、在体表温度下的黏度和屈服值、触变性）为指标,优化凝胶剂成型处方。结果：祛斑凝胶剂基质最佳处方为卡波姆9 401.0 g,甘油5 mL,pH 5~6。结论：通过建立凝胶基质质量与凝胶流体学参数回归模型,能直接反应各因素影响作用,为凝胶基质处方的筛选能提供一定的参考依据,采用该方法制备的祛斑凝胶剂均匀细腻,黏度适中,触变性良好。     

基于相同载体体系的中药成分自乳化制剂的制备及其体外透皮吸收特性考察

目的:制备同时适合于黄芩素、黄连素及大蒜素3种中药成分的自乳化载体体系,并考察这3种自乳化制剂的体外透皮吸收效果。方法:采用饱和溶解度法、伪三元相图法、正交试验筛选最佳的空白处方组成及基质用量。以Franz扩散池和离体大鼠皮肤进行体外透皮吸收试验,采用HPLC分别测定3种自乳化制剂中黄芩素、黄连素及大蒜素的累积透皮渗透量,并分别与黄芩素散剂、黄连素散剂及大蒜素散剂进行比较。结果:最佳处方为油酸乙酯-聚氧乙烯氢化蓖麻油40-聚乙二醇400载体体系,所形成的自乳化制剂粒径适宜,其微观形态呈较规整的球形。透皮吸收10 h,黄芩素、黄连素及大蒜素3种自乳化制剂的药物透皮速率分别为6.898 6,7.600 4,190.040μg·cm~(-2)·h~(-1),累积透皮渗透量分别为71.38,85.54,1 795.16μg·cm~(-2)。结论:成功制备了不同种类中药成分均能使用的自乳化载体体系,且该自乳化制剂的体外透皮吸收效果良好,可为后续中药复方自乳化制剂的制备及其透皮给药吸收研究提供实验依据。     

强力霉素凝胶治疗大鼠口腔溃疡的实验研究

目的研究强力霉素对口腔溃疡的治疗作用,为临床用药提供指导。方法采用60%水醋酸酸蚀SD大鼠口腔颊黏膜建立大鼠溃疡模型。取36只造模成功大鼠随机分为3组,每组12只,分别给予高低剂量强力霉素及空白凝胶作局部治疗,分别于用药第2天、第4天、第6天每组处死4只大鼠,经过切取标本,石蜡包埋,制片,HE染色、麦氏染色和免疫组化染色后,于光镜下进行观察。结果用药后,强力霉素高低剂量组较对照组炎性渗出明显减少,充血情况明显减轻,胶原纤维降解、MMP-9的表达明显减少,溃疡愈合更快。结论强力霉素可能是通过抑制MMP-9的表达,减少胶原纤维的降解,促进口腔溃疡愈合。     

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.     

异种(牛)脱细胞真皮基质-游离空肠复合体构建实验研究

目的 研究异种(牛)脱细胞真皮基质-游离空肠复合体的构建技术,以期解决游离空肠移植重建长段气管术后肠腺分泌的问题。 方法 选择10只杂种犬,制备去上皮游离空肠段,将剪成合适大小的异种(牛)脱细胞真皮基质覆盖于游离空肠基底膜表面,并用覆膜镍钛合金支架支撑固定,将构建好的复合体移至腹膜外与腹部皮肤之间,分别于术后7 d、14 d、1个月、3个月和6个月后取出,查看复合体的生长情况。 结果 10只实验犬中,有1只因肠粘连和伤口感染死亡而未能完成实验,余9只实验犬术后存活良好。术后7 d、14 d肉眼观察和病理检查,在游离空肠内表面均见有异种(牛)脱细胞真皮基质成分,表面黏膜层可见部分鳞状上皮化生;术后1个月、3个月、6个月肉眼和病理检查均未再发现异种(牛)脱细胞真皮基质成分,游离空肠内表面几乎全部化生为复层鳞状上皮。 结论 合适大小的异种(牛)脱细胞真皮基质覆盖在去上皮游离空肠内表面,可以促进游离空肠内表面的鳞状上皮化生,抑制肠腺分泌。覆膜镍钛记忆合金支架有一定的弹性,可以很好的对异种(牛)脱细胞真皮基质-去上皮游离空肠复合体起到支撑固定作用。     

细胞外基质蛋白和转化生长因子β2共同作用诱导人视网膜色素上皮细胞向肌纤维母细胞转化

目的 了解转化生长因子β2（TGFβ2）和细胞外基质（ECM）调节人胚胎视网膜色素上皮（hfRPE）细胞向肌纤维母细胞分化的作用，确定这种调节的信号传导机制。 方法 hfRPE细胞培养于由ECM包被或未包被的培养皿上，培养液中加入或不加入TGFβ2，用免疫组织化学、流式细胞仪、蛋白印迹技术检测α平滑肌机动蛋白（α-SMA）的表达。在培养液中分别加入calphostin C, 染料木黄铜（genistein）, PD98059和渥曼青霉素（Wortmannin），测定α-SMA的表达。 结果 hfRPE细胞培养于ECM包被的培养板上，培养液中加入TGFβ2后，出现明显的形态学改变，包括细胞伸展变长，可见肌动蛋白微丝的形态。流式细胞仪及免疫细胞化学检测结果显示，培养液中加入TGFβ2可明显增加α-SMA的表达，并与剂量成正相关。当TGFβ2 的刺激浓度为50 ng/ml时，与培养于未包被的培养板上的hfRPE细胞相比，用纤维连接蛋白（FN）包被培养板后，〖JP1〗总的平均荧光强度（TMFI）增加（38.01±1.14）%（P<0.05）。蛋白印迹技术检测显示同样的结果。而上述效应可以大部分被蛋白激酶C（PKC）通路抑制剂calphostin C（10 nmol/L）抑制（P<0.01）。 结论 TGFβ2可诱导hfRPE细胞向肌纤维母细胞转化，并与其剂量成正相关，这种作用可被FN加强。TGFβ2和ECM的这种调节作用可能是通过PKC细胞内信号传导通路而发挥作用 。 (中华眼底病杂志, 2006, 22: 328-332)     

Inhibitory effect of Ginkgo biloba extract on hyperhomocysteinemia-induced intimal thickening in rabbit abdominal aorta after balloon injury

Ginkgo biloba extract (GBE) has been widely used to treat cardiovascular and cerebrovascular disorders. Hyperhomocysteinemia (Hhcy) is associated with the risk of atherosclerosis and restenosis after angioplasty. The objective of this study was to investigate whether GBE could attenuate the Hhcy-induced intimal thickening after balloon injury in rabbit abdominal aorta. It was observed in this study that GBE could decrease the neointima area (NA) and the ratio of the neointima area to the media area (NA/MA), down-regulate the mRNA expression of matrix metalloproteinase-9 (MMP-9) and up-regulate the protein expression of p21 (WAF1/CIP1) (p21). It suggests that GBE can reverse the Hhcy-induced neointima formation in rabbits following balloon injury, and the suppressive effect of GBE on the migration and proliferation of vascular smooth muscle cells (VSMCs) may contribute to its actions.     

Matrix metalloproteinase-1 promoter polymorphism and epithelial ovarian cancer: does ethnicity matter?

AIM: To estimate the relationship between matrix metalloproteinase (MMP)-1 promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in Korean women and to clarify the ethnic difference in genotype distribution of this polymorphism. METHODS: Single nucleotide polymorphism (SNP) of MMP-1 promoter -1607 region in 133 EOC patients and 332 cancer-free patients were investigated. Then the associations of this polymorphism with EOC or its clinicopathological parameters were analyzed. In addition, genotype distributions of this polymorphism in Korean women were compared with those of other races by extracting data from the previously published literature. RESULTS: We found no relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian cancer in a Korean population. Furthermore, we found ethnicity-dependent differences in genotype distributions and allele frequencies by comparison with previous articles on this topic. We report significant ethnic differences in the genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp polymorphism. CONCLUSION: Our results indicate that MMP-1-1607 bp polymorphism shows ethnic diversity, and that the hypothesis that this polymorphism is associated with epithelial ovarian cancer is not supported by this study in a Korean population. Moreover, this finding concurs with results obtained in white Americans and Europeans.