DL—聚乳酸微球大鼠体内的降解

采用凝胶渗透色谱，通过观察ＤＬ－聚乳酸分子量的变化，对两种不同分子量的ＤＬ－ＰＬＡ微球在大鼠体内的降解进行了研究，探讨分析了降解机理。结果表明：ＤＬ－ＰＬＡ微球在大鼠体内的降解为简单本体水解；初始ＤＬ－ＰＬＡ分子量的不同对降解速率影响不显著。     

降解材料聚乳酸－聚乙二醇生物相容性的研究

作者对国产新型生物医用可降解材料ＤＬ—聚乳酸—聚乙二醇共聚物（ＰＥＬＡ）进行了系统的生物学评价。结果表明：降解材料ＰＥＬＡ无全身毒性、无热原和细胞毒性、无溶血（溶血率小于５％）、对皮肤和眼粘膜无刺激、不引起致敬反应、对骨髓多染红细胞无影响。体内植入２８０天，材料基本降解完全，材料周围纤维囊壁厚度逐渐变薄，炎症细胞反应减轻。因此，可认为降解材料ＰＥＬＡ有良好的生物相容性。     

甲壳素和甲壳胺对聚乳酸体外降解的影响

考察了ＤＬ－聚乳酸（ＤＬ－ＰＬＡ）／甲素（ＣＨＩ）,ＤＬ－ＰＬＡ／甲壳胺（ＣＨＳ）两种复合物在生理盐水降解过程中生理盐水的ｐＨ值、试样的失重率和外观形态以及ＤＬ－ＰＬＡ分子量的变化,结果表明：ＣＨＩ和ＣＨＳ对ＤＬ－ＰＬＡ的降解速度有明显的抑制作用,并对抑制机理进行了探讨。     

新型聚酯醚材料体内外降解和组织反应

作者采用凝胶渗透色层法，扫描电和光学显微镜观察，对新疆聚酯醚（聚癸二酸－丁二醇－聚乙二醇共聚物）生物降触怒地体内外降解和体内植放相容性研究。材料在体内１５０天时，该材料重量和分子量丧失５０％左右，２８０天分别丧失８６％和８９％；在此观察人材料与组织相容性良好而材料体外较体内缓慢，对二乾间的差异和可能影响降解的因素进行探讨并与另一咱新型聚酯醚材料（ＤＬ－聚乳酸－聚乙二醇共聚物）进行比较，结果显示聚癸     

降解材料聚乳酸—聚乙二醇生物相容怀的研究

作者对国产新型生物医用可降解材料ＤＬ－聚乳酸－聚乙二醇共聚物进行了系统的生物学评价。结果表明：降解材料ＰＥＬＡ无全身毒性、无热原和细胞毒性、无溶血、对皮肤和眼粘膜无刺激、不引起致敏反应，对骨髓多染红细胞无影响。     

高胆固醇血症大鼠LDL受体与apoA－1mRNA的水平变化及苯甲酸雌二醇对其影响

本文研究了实验性高胆固醇血症大鼠肝及小肠中低密度脂蛋白（ＬＤＬ）受体ｍＲＮＡ和载脂蛋白（ａｐｏ）Ａ－１ｍＲＮＡ的水平变化以及苯甲酸雌二醇（ＥＢ）对二者的影响。发现高脂（ＨＣ）组肝及小肠ＬＤＬ受体ｍＲＮＡ水平分别低于正常组５０％和６０％（Ｐ＜０．０５），小肠ａｐｏＡ－１ｍＲＮＡ水平低于正常组５８％（Ｐ＜０．０５），此时血清总胆固醇（ＴＣ）及ＬＤＬ胆固醇（ＬＤＬ－ｃ）均明显高于正常组（Ｐ＜０．０１），血清ａｐｏＡ－１低于正常组（Ｐ＜０．０５）。ＨＣ＋ＥＢ组血清ＴＣ及ＬＤＬ－ｃ明显低于ＨＣ组，而肝ＬＤＬ受体ｍＲＮＡ水平则显著高于ＨＣ组，为ＨＣ组的３．５倍（Ｐ＜０．００２）。结果提示：（１）高胆固醇负荷时细胞可通过转录水平下行调节ＬＤＬ受体；（２）小肠可能在ａｐｏＡ－１的代谢中起重要作用；（３）ＥＢ可能通过诱导肝ＬＤＬ受体基因表达而降血脂。     

高胆固醇血症大鼠LDL受体与apoA—1mRNA的水平变化及苯甲…

本文研究了实验性高胆固醇血症大鼠肝及小肠中低密度脂蛋白（ＬＤＬ）受体ｍＲＮＡ和载脂蛋白（ａｐｏ）Ａ－１ｍＲＮＡ的水平变化以及苯甲酸雌二醇（ＥＢ）对二者的影响。发现高脂（ＨＣ）组肝及小肠ＬＤＬ受体ｍＲＮＡ水平分别低于正常组５０％和６０％（Ｐ〈０．０５），小肠ａｐｏＡ－１ｍＲＮＡ水平低于正常组５８％（Ｐ〈０．０５），此时血清总胆固醇（ＴＣ）及ＬＤＬ胆固醇（ＬＤＬ－ｃ）均明显于正常组（Ｐ〈０．０１），血     

聚乙二醇修饰重组人白细胞介素-2及其生物学特性

采用聚乙二醇活性酯（ＰＥＧ－５０００）化学修饰重组人白细胞介素－２（ｒＩＬ－２）及修饰后复性制得修饰产物ＰＥＧ－ｒＩＬ－２。ＰＥＧ－ｒＩＬ－２系列研究：经ＳＤＳ－ＰＡＧＥ和ＣＴＬＬ－２短期细胞培养结合３Ｈ－ＴｄＲ掺入法测定，ＰＥＧ－ｒＩＬ－２分子量为２５ｋＤ，生物活性保留６９．７％；采用ＬＤＨ释放法测定证实ＰＥＧ－ｒＩＬ－２激活的ＬＡＫ细胞对人体肝癌细胞ＢＥＬ－７４０２和Ｋ５６２细胞的杀伤作用和ｒＩＬ－２相近甚至强于ｒＩＬ－２；小鼠体内的药代动力学研究表明，经静脉给药后，ＰＥＧ－ｒＩＬ－２较ｒＩＬ－２的系统清除率降低了７．７倍，清除相半衰期延长了１２倍。提示ＰＥＧ修饰ｒＩＬ－２后可能改变目前肿瘤免疫法中ｒＩＬ－２的剂量方案，减少其用量和不良反应。     

抗氧化剂PDTC抑制氧化的低密度脂蛋白诱导的人肾小球系膜细胞NF_(-k)B活化

目的 研究氧化的低密度脂蛋白（Ｏｘ－ＬＤＬ）对体外培养的人肾小球系膜细胞（ＨＭＣ）核因子－ＫＢ（ＮＦ－ＫＢ）活化的影响，以及抗氧化剂毗咯二硫氨基甲酸酯（Ｐ ＤＴＣ）对ＮＦ－ＫＢ活化的抑制作用，探讨ＯＸ－ＬＤＬ介导肾损害的基因调控机制及抗氧化剂ＰＤＴＣ防治脂质肾损害的可能性。方法 将Ｏｘ－ＬＤＬ或ＰＤＴＣ与ＨＭＣ共培养后，提取细胞核蛋白进行凝胶迁移率变动分析（ＥＭＳＡ）检测ＮＦ－ＫＢ的活化，用细胞ＥＬＩＳＡ法检测细胞内ＩＫＢα蛋白含量的变化，反映ＩＫＢα的降解及免疫组化染色检测细胞内的Ｐ６５向核转位。结果 正常对照组未见ＮＦ－ＫＢ活化，当用不同浓度（１０、２５、５０及１００ｍｇ／Ｌ）的Ｏｘ－ＬＤＬ，刺激肾小球系膜细胞 ｌｈ后，均可引起细胞 ＮＦ－ＫＢ活化及 ＩＫＢα降解。与对只组相卜较差异显著（ｐ＜０．０５），以５０ｍｇ／Ｌ 的ＯＸ－ＬＤＬ刺激ＨＭＣ１ｈ，ＮＦ－ＫＢ活化及 ＩＫＢα降解最明显。ＮＦ－ＫＢ活化的同时，伴有Ｐ６５由胞浆向胞核的转位。１００μｍｏｌ／Ｌ ＰＤＴＣ，能明显抑制 ＮＦ－ＫＢ的活化、ＩＫＢα降解（ｐ＜０．０１）及 Ｐ６５的核转位。结论Ｏｘ－ＬＤＬ。能诱导ＨＭＣ的ＩＫＢαａ降解、Ｐ６５的核转位，最终使Ｎ     

神经肽PACAP拮抗低密度脂蛋白对内皮细胞的损伤

以体外培养的内皮细胞（ＥＣ）为模型，观察神经肽ＰＡＣＡＰ对ＥＣ受低密度脂蛋白（ＬＤＬ）损伤的影响，结果表明，单纯加入ＬＤＬ至培养液时，ＥＣ出现胞体收缩，细胞膜破坏等明显的损伤性改变，在条件培养液中组织型溶酶原激活物（ｔ－ＰＡ）的含量显著降低，脂质过氧化物（ＭＤＡ）的产生显著增加（Ｐ〈０．０１）；而在培养液中同时加有ＰＡＣＡＰ（１０＾－８ｍｏｌ／Ｌ）的ＥＣ，形态损伤不明显，培养液中ｔ－ＰＡ的含量升高     

聚乳酸/聚乙二醇-聚乳酸新型亲水支架的制备与研究

利用热致相分离/粒子沥滤结合法,制备了聚乳酸(PDLLA)以及聚乳酸与聚乙二醇-聚乳酸共聚物(PELA)复合的PDLLA/PELA组织工程支架。讨论了聚乙二醇(PEG)分子量、PELA含量及组成比对于支架内部结构、力学性能、降解行为和细胞毒性的影响。结果表明,热致相分离/粒子沥滤结合法制备的支架,具有100~250μm大孔与5~40μm小孔兼备的特殊内部结构,PEG含量愈高、PEG分子量愈小,支架的孔隙率愈大。PDLLA/PELA比率的减小,PEG/PLA比率的增大会引起支架力学性能的下降和降解的加速。材料无细胞毒性。当支架中PDLLA/PELA为3∶1,PEG 5000/PLA为25∶75时,其内部孔形态最为理想。     

Biocompatibility and degradation of poly(ether-ester) microspheres: in vitro and in vivo evaluation

Microspheres of a hydrophobic and a hydrophilic poly(ether–ester) copolymer were evaluated for their in vitro and in vivo biocompatibility and degradation. The microspheres prior to and after sterilization were tested for in vitro cytotoxicity. The in vivo biocompatibility of the poly(ethylene glycol) terephthalate and poly(butylene terephthalate) (PEGT/PBT) microspheres was evaluated subcutaneously and intramuscularly for 24 weeks in rabbits. The in vivo degradation of the microspheres was studied microscopically and compared to the in vitro degradation. The in vitro and in vivo studies showed the biocompatibility of the microspheres of both the hydrophobic and the hydrophilic PEGT/PBT copolymer. Extracts of these microspheres showed no cytotoxic reactivity in the in vitro cytotoxicity test. Sterilization of the microspheres by gamma irradiation did not affect the cytotoxicity. PEGT/PBT microspheres injected subcutaneously and intramuscularly in rabbits showed a mild tissue response in vivo, in terms of the inflammatory response, the foreign body reaction and the granulation tissue response. Although an in vitro degradation experiment showed a decrease in molecular weight due to hydrolysis, the in vivo degradation of the microspheres was slower than previously published.     

聚乙交酯丙交酯体内外生物降解性能的相关研究

通过对聚乙交酯丙交酯 (PGL A)进行体内和体外生物降解性的实验研究 ,探讨两种降解过程之间的关联性。体外实验是将 PGL A材料 (1cm× 1cm)分别浸泡在人工唾液和 PBS溶液中 ,体内 (动物 )试验是将材料直接植入 Wistar大白鼠的皮下组织 ,浸泡后或植入后 1～ 10周 ,每周计算材料的质量损耗率 ,每 2周进行分子量测定。实验结果显示 :PGL A材料在人工唾液中的降解要快于在 PBS液中的降解 ;材料质量损耗的发生慢于分子量的变化 ;体外的降解周期大约为 9～ 10周 ,体内降解周期为 8周左右 ,体内组的降解速率是体外组的 1.33倍。结论为PGL A体外降解主要是化学降解过程 ,通过酯键的水解来进行。体内降解过程中 ,应力环境和生物因素都会对材料的降解动力学产生影响 ,使降解过程明显加快 ,但体内和外降解都符合脂肪族聚酯降解的动力学模型 ,PGL A的体内外生物降解性之间存在一定的相关性。     

Tissue anti-adhesion potential of biodegradable PELA electrospun membranes

The most commonly used anti-adhesion device for separation and isolation of wounded tissues after surgery is the polymeric membrane. In this study, a new anti-adhesion membrane from polylactide–polyethylene glycol tri-block copolymer (PELA) has been synthesized. The synthesized copolymers were characterized by gel permeation chromatography and ¹H nuclear magnetic resonance spectroscopy. PELA membrane was prepared by electrospun. The prepared copolymer membranes were more flexible than the control poly-d-l-lactic acid (PDLLA) membrane, as investigated by the measurements of glass transition temperature. Its biocompatibility and anti-adhesion capabilities were also evaluated. In vitro cell adhesions on the PELA copolymer membrane and PDLLA membrane were compared by the culture of mouse fibroblasts L929 on the surfaces. For in vivo evaluation of tissue anti-adhesion potential, the PDLLA and PELA copolymer membranes were implanted between cecum and peritoneal wall defects of rats and their tissue adhesion extents were compared. It was observed that the PELA copolymer membrane was very effective in preventing cell or tissue adhesion on the membrane surface, probably owing to the effects of hydrophilic polyethylene glycol.     

聚乳酸、乳酸乙醇酸共聚物的制备及其体外降解

以外消旋乳酸、左旋乳酸和乙醇酸为原料,制备高纯度交酯单体丙交酯和乙交酯,以辛酸亚锡引发在高真空条件下本体熔融开环聚合,制得一系列不同分子量的聚乳酸均聚物和不同配比的乳酸乙醇酸共聚物,并用核磁共振氢谱、凝胶渗透色谱、差示扫描量热仪等手段对聚合产物的结构和性能进行分析表征.将溶液涂膜法制备的聚乳酸均聚物和乳酸乙醇酸共聚物薄膜置于Hank's人工模拟体液中降解试验,记录聚合物薄膜的失重和黏度及表面形貌变化,考察其体外降解规律,筛选适合作为冠脉支架表面载药涂层的聚合物,以推测其在人体内的降解行为.     

天冬氨酸—谷氨酸共聚物的合成、表征及性质研究

制备了L－天冬氨酸－L－谷氨酸共聚物（摩尔比为8：2）,将3－氨基丙醇接入材料母体,制得聚－（3－羟丙基）－L－天冬氨酸－谷氨酸材料（PHPAG）。对材料用核磁共振、X-ray衍射、DSC差热分析及元素分析等作了表征,以葡聚糖标准品为相对分子量,用凝胶色谱法测定材料的分子量。材料注入小鼠体内后进行了急性毒性、血液参数、微核等生物相容性检测,结果表明材料为无毒材料。用不同水解酶对材料作了体外酶解实验,实验显示酶对共聚材料有一定程度的酶解。对材料在不同pH值、光照、湿度等条件下进行了稳定性实验,结果表明材料的在实验条件下是稳定的。     

骨髓炎治疗用缓释制剂的制备及体外抑菌活性研究

骨髓炎的定点缓释给药治疗是重要的生物医学问题,关键是要制备高效的缓释药棒。我们采用热熔法,以聚(二聚酸(十四烷二酸)共聚物[P(DA-TA),WDA:WTA=50:50]为药物缓释材料,硫酸庆大霉素为模型药物,制备了硫酸庆大霉素-聚酸酐缓释药棒,以期最终用于骨髓炎的定点缓释给药治疗。初步的制剂稳定性研究表明,在室温干燥条件下,该缓释药棒具有良好的制剂稳定性。体外释药结果表明,37℃时,该缓释药棒在蒸馏水中、0．9％生理盐水中和0．1 mol／L pH7．4 PBS中具有明显缓释作用,其体外释药动力学均符合一级动力学方程和Peppas方程。抑菌活性实验表明,该缓释药棒对骨髓炎常见致病菌:金黄色葡萄球菌及大肠杆菌有长达60 d的抑制作用。该类硫酸庆大霉素-聚酸酐缓释药棒具有良好的制剂稳定性和长达60 d的抑菌活性,可望用于骨髓炎治疗领域。     

In vitro and in vivo degradability and cytocompatibility of poly(l-lactic acid) scaffold fabricated by a gelatin particle leaching method

Porous poly(l-lactic acid) (PLLA) scaffolds fabricated by a gelatin particle-leaching technique have good mechanical property and cytocompatibility, as demonstrated by a previous in vitro study. Here we investigate further the in vitro degradation of the scaffolds in terms of weight loss, water uptake, weight-average molecular weight, thermal behavior and morphology during a 39 week period in phosphate-buffered saline. The water uptake decreased dramatically during the initial stage due to release of the remaining gelatin, and then increased slightly with degradation time. The weight-average molecular weight decreased linearly as a function of time, while the crystallinity steadily increased with slightly decreased melting temperature. After degradation, many defects and big holes were seen in the scaffolds by scanning electron microscopy. Cartilage regeneration and scaffold disappearance in vivo were compared by implanting the construct into nude mice for 30-120 days. While the scaffolds maintained their intact pore structure after 23 weeks of degradation in vitro, they almost disappeared in vivo at the same time, implying a faster degradation rate in vivo. By 120 days after implantation, the scaffolds were hardly seen in the newly formed cartilage-like tissue. The regenerated cartilages could not maintain their predesigned shape after a long period of in vivo culture due to the weakening of the mechanical strength of the constructs as a result of PLLA degradation. The regions occupied initially by PLLA scaffold were filled later by collagen type II secreted by the chondrocytes, but with no evident basophilic proteoglycan.     

Poly(D,L-lactide) foams modified by poly(ethylene oxide)-block-poly(D,L-lactide) copolymers and a-FGF: in vitro and in vivo evaluation for spinal cord regeneration

The first goal of this study was to examine the influence that poly(ethylene oxide)-block-poly(D,L-lactide) (PELA) copolymer can have on the wettability, the in vitro controlled delivery capability, and the degradation of poly(D,L-lactide) (PDLLA) foams. These foams were prepared by freeze-drying and contain micropores (10 microm) in addition of macropores (100 microm) organized longitudinally. Weight loss, water absorption, changes in molecular weight, polymolecularity (Mw/Mn) and glass transition temperature (Tg) of PDLLA foams mixed with various amounts of PELA were followed with time. It was found that 10wt% of PELA increased the wettability and the degradation rate of the polymer foams. The release of sulforhodamine (SR) was compared for PDLLA and PDLLA-PELA foams in relation with the foam porosity. An initial burst release was observed only in the case of the 90:10 PDLLA/PELA foam. The ability of the foam of this composition to be integrated and to promote tissue repair and axonal regeneration in the transected rat spinal cord was investigated. After implantation of ca. 20 polymer rods assembled with fibrin-glue, the polymer construct was able to bridge the cord stumps by forming a permissive support for cellular migration, angiogenesis and axonal regrowth.