海藻酸钠-多聚赖氨酸-海藻酸钠微囊内细胞浓度与胰岛素和C肽的释放

背景：微囊化已经普遍应用于各种实验研究,微囊包裹的干细胞治疗糖尿病问题也成为当今的热点,但是囊内包裹的细胞浓度与胰岛素释放量的关系成为目前需要解决的问题之一。目的：运用海藻酸钠-多聚赖氨酸-海藻酸钠微囊包裹胰岛素产生细胞,观察细胞浓度对胰岛素和C肽释放情况的影响。方法：制备大鼠胰腺损伤提取物,将小鼠骨髓间充质干细胞诱导分化为胰岛素产生细胞。免疫荧光和双硫腙染色鉴定诱导后细胞内胰岛素的表达。然后将胰岛素产生细胞制成浓度分别为1×107L-1,5×107L-1,1×108L-1,5×108L-1,1×109L-1,5×109L-1的细胞悬液,气体吹喷法制成微囊,用6-羧基乙二酸荧光素检测囊内细胞活力,用葡萄糖刺激微囊内细胞检查其胰岛素和C肽的分泌情况。结果与结论：胰腺损伤提取物诱导后双硫腙染色和细胞免疫荧光鉴定出胰岛素产生细胞内有胰岛素的表达;胰岛素产生细胞制成的微囊直径约为400μm,大小均一,6-羧基乙二酸荧光素检测到囊内细胞的活力很好。用葡萄糖刺激不同细胞浓度的微囊,发现细胞浓度为1×108L-1时,胰岛素和C肽的分泌达到最高。     

海藻酸钠-多聚赖氨酸-海藻酸钠微囊化大鼠卵巢细胞腹腔异体移植以及对肾上腺的影响

背景:应用海藻酸钠-多聚赖氨酸-海藻酸钠微囊技术包裹细胞进行异体移植,被证明是一种可避免受体产生免疫排异的有效方法.目的:观察海藻酸钠-多聚赖氨酸-海藻酸钠微囊化卵巢细胞种植于去卵巢大鼠腹腔后对受体大鼠肾上腺的影响.设计、时间及地点:随机对照动物实验,于2007-03/2008-09在首都医科大学生殖医学研究中心完成.材料:取Wistar大鼠卵巢分离培养卵巢细胞,进行微囊化处理,制备包裹卵巢细胞的海藻酸钠-多聚赖氨酸-海藻酸钠微囊.方法:将40只雌性Wistar大鼠随机分为4组:去势组于无菌条件下切除双侧卵巢;微囊移植组手术摘除双侧卵巢后腹腔移植包裹卵巢细胞的海藻酸钠-多聚赖氨酸-海藻酸钠微囊;雌激素替代治疗组手术摘除双侧卵巢后腹腔注射乙烯雌酚 0.2 mg/kg,每3 d注射1次.正常对照组不进行任何处理.主要观察指标:干预后30 d放射免疫法检测大鼠血清中雌激素水平,观察肾上腺切片的形态学特点,并利用免疫组织化学SP法检测各组大鼠肾上腺皮质各层增殖细胞核抗原表达变化.结果:①放射免疫法检测正常对照组,雌激素替代治疗组以及微囊移植组雌激素水平明显高于去势组,而正常对照组,微囊移植组,雌激素替代治疗组之间雌激素水平差异无显著性意义.②去势组肾上腺皮质网状带增厚,网状带与球束状带比值增大,束状带和网状带增殖细胞核抗原阳性表达都增加;而微囊移植组及雌激素替代治疗组增殖细胞核抗原阳性细胞明显低于去势组,差异具有显著性意义.结论:微囊化大鼠卵巢细胞异体移植后,可在受体大鼠体内继续合成和分泌雌二醇,所分泌的雌激素可以纠正肾上腺皮质因卵巢摘除而导致的形态改变,并与雌激素替代治疗疗效相近.     

基因转染骨髓间充质干细胞诱导分化为胰岛素分泌细胞

骨髓间充质干细胞在体外一定条件下分化成为胰岛细胞,既可以解决胰岛移植中供体紧缺的问题,又能够通过自体移植避免免疫排斥,还将避开胚胎干细胞研究所涉及的伦理道德问题,是治疗糖尿病的理想干细胞来源.研究发现可以将胰岛素基因及其他必需的基因直接导入来自糖尿病患者的原代细胞或其他成体干细胞如肝细胞、肠道上皮K细胞、成纤维细胞及肝脏肿瘤细胞等,使其转变为胰岛素分泌细胞即转基因的胰岛素分泌细胞.目前国际上主要的研究方向是如何将胰岛素基因有效地导入靶细胞,并使之呈生理模式表达.     

脐血C肽，胰岛素浓度与胎儿发育的关系

为了明确胰岛素在胎儿发育中所起的作用 ,以便寻找能比较直接反映胎儿生长状态的生化指标用于临床 ,1999年 6～12月 ,我院产科对胎儿脐静脉血Ｃ肽、胰岛素浓度与孕龄、胎儿体重的关系进行了初步探讨 ,现将有关结果报道如下。1　资料与方法1 1　被检对象的选择和标本的采集　随机选择正常妊娠 36～ 41周的孕妇 181例 ,除外月经紊乱、双胎、胎儿发育缺陷、其他并发症及内科合并症 ;另选择 11例临床诊断为妊娠糖尿病的孕妇 (ＧＤＭ) ,被检孕妇未发现有胎儿发育畸形 ,并无其他母体合并症。从末次月经来潮日算起 ,结合早孕期Ｂ超检查结果 ,确定其…     

鼠脑C6胶质瘤细胞上清液诱导人骨髓间充质千细胞向神经元样细胞的分化

目的:观察人骨髓间充质干细胞经鼠脑C6胶质瘤细胞上清液诱导后向神经元样细胞方向的分化情况.方法:取肝素抗凝人骨髓血,Percoll梯度法体外分离培养骨髓间充质干细胞,胰酶消化后传代扩增.取第4～6代骨髓间充质干细胞,当细胞达90%融合时,按2×103/孔接种于24孔板内,第2天分为两组,诱导组用含有50%C6胶质瘤细胞上清液的完全培养基(含体积分数为0.1胎牛血清的L-DMEM培养基)诱导,每隔2 d换液1次;对照组单纯加入完全培养基进行培养.诱导后3 d,两组细胞采用S-P法进行免疫细胞化学染色,检测神经元特异性标志物的表达.结果:诱导24 h后,诱导组多数骨髓间充质干细胞表现出典型的神经元样外观,对照组细胞形态无明显变化.诱导3 d后,诱导组神经元烯醇化酶阳性细胞率显著高于对照组(P<0.01);诱导组神经丝蛋白阳性细胞率为(44.2±2.4)%,对照组为阴性:两组胶质纤维酸性蛋白均呈阴性表达.结论:鼠脑C6胶质瘤细胞上清液可成功诱导入骨髓间充质干细胞向神经元样细胞分化.     

海藻酸钠-多聚赖氨酸-海藻酸钠微囊化大鼠卵巢细胞腹腔异体移植以及对肾上腺的影响术

背景：应用海藻酸钠-多聚赖氨酸-海藻酸钠微囊技术包裹细胞进行异体移植,被证明是一种可避免受体产生免疫排异的有效方法。目的：观察海藻酸钠-多聚赖氨酸-海藻酸钠微囊化卵巢细胞种植于去卵巢大鼠腹腔后对受体大鼠。肾上腺的影响。设计、时间及地点：随机对照动物实验,于2007—03,2008—09在首都医科大学生殖医学研究中心完成。材料：取Wistar大鼠卵巢分离培养卵巢细胞,进行微囊化处理,制备包裹卵巢细胞的海藻酸钠-多聚赖氨酸-海藻酸钠微囊。方法：将40只雌性Wistar大鼠随机分为4组：去势组于无菌条件下切除双侧卵巢;微囊移植组手术摘除双侧卵巢后腹腔移植包裹卵巢细胞的海藻酸钠-多聚赖氨酸-海藻酸钠微囊;雌激素替代治疗组手术摘除双侧卵巢后腹腔注射乙烯雌酚0．2mg／kg,每3d注射1次。正常对照组不进行任何处理。主要观察指标：干预后30d放射免疫法检测大鼠血清中雌激素水平,观察肾上腺切片的形态学特点,并利用免疫组织化学SP法检测各组大鼠肾上腺皮质各层增殖细胞核抗原表达变化。结果：①放射免疫法检测正常对照组,雌激素替代治疗组以及微囊移植组雌激素水平明显高于去势组,而正常对照组,微囊移植组,雌激素替代治疗组之间雌激素水平差异无显著性意义。②去势组肾上腺皮质网状带增厚,网状带与球束状带比值增大,束状带和网状带增殖细胞核抗原阳性表达都增加;而微囊移植组及雌激素替代治疗组增殖细胞核抗原阳性细胞明显低于去势组,差异具有显著性意义。结论：微囊化大鼠卵巢细胞异体移植后,可在受体大鼠体内继续合成和分泌雌二醇,所分泌的雌激素可以纠正肾上腺皮质因卵巢摘除而导致的形态改变,并与雌激素替代治疗疗效相近。     

骨髓间充质干细胞向胰岛素分泌细胞诱导分化的动态观察

目的:探讨体外诱导骨髓间充质干细胞向胰岛素分泌细胞分化的可能性,并观察其动态变化。方法:实验于2005-09/2007-03在山东大学齐鲁医院完成。①标本来源:骨髓标本15例来自山东大学齐鲁医院成人骨髓检查结果正常者,均签署捐献同意书。②实验方法:无菌条件下取骨髓2.0～5.0mL,采用percoll分离液和贴壁法获得纯化的成人骨髓间充质干细胞。③实验评估:流式细胞仪行细胞表面抗原检测,在适当的条件下诱导其分化为成骨细胞和脂肪细胞。采用两步法向胰岛素分泌细胞诱导,观察其在碱性成纤维细胞生长因子、活化素A、胰岛素样生长因子、尼克酰胺等因子刺激下向胰岛素分泌细胞分化的动态变化。双硫踪染色鉴定胰岛样细胞团,酶联免疫吸附试验检测细胞分泌胰岛素的情况,RT-PCR检测胰岛细胞特异基因的表达。结果:①骨髓间充质干细胞的生长特性及免疫表型:分离培养获得的贴壁细胞,呈形态均一的梭形,流式细胞仪检测CD34、CD45表达阴性,CD29、CD44表达阳性。②向成骨细胞和脂肪细胞的诱导分化:此类细胞经茜素红染色、油红O染色均呈阳性,可诱导分化为成骨细胞和脂肪细胞。③向胰岛素分泌细胞的诱导分化:第1步诱导后出现细胞簇,双硫腙染色不着色,胰岛素分泌量少,仅检测到PDX-1基因的表达,证实其为胰岛前体细胞。第2步诱导后细胞簇数目逐渐上升,至诱导14d大部分细胞簇经双硫腙染色都呈红色。④诱导后培养上清中胰岛素含量:诱导第3,7,14,21天的胰岛素分泌量分别为(15.3±4.9),(34.1±5.6),(40.4±5.3),(39.8±5.1)mU/L。⑤胰岛细胞特异基因的表达:诱导7d仅检测到PDX-1基因的表达,insulin1、insulin2和Glut2基因均不表达。诱导14,21d检测到insulin2、PDX-1基因表达,insulin1基因弱表达,Glut2基因不表达。结论:体外分离、纯化得到的骨髓间充质干细胞诱导7d可分化出胰岛前体细胞,不具功能性;诱导14d后可成功地分化出成熟的具有功能性的胰岛素分泌细胞。     

鼠脑C6胶质瘤细胞上清液诱导人骨髓间充质干细胞向神经元样细胞的分化

目的:观察人骨髓间充质干细胞经鼠脑C6胶质瘤细胞上清液诱导后向神经元样细胞方向的分化情况。方法:取肝素抗凝人骨髓血,Percoll梯度法体外分离培养骨髓间充质干细胞,胰酶消化后传代扩增。取第4~6代骨髓间充质干细胞,当细胞达90%融合时,按2×103/孔接种于24孔板内,第2天分为两组,诱导组用含有50?胶质瘤细胞上清液的完全培养基(含体积分数为0.1胎牛血清的L-DMEM培养基)诱导,每隔2d换液1次;对照组单纯加入完全培养基进行培养。诱导后3d,两组细胞采用S-P法进行免疫细胞化学染色,检测神经元特异性标志物的表达。结果:诱导24h后,诱导组多数骨髓间充质干细胞表现出典型的神经元样外观,对照组细胞形态无明显变化。诱导3d后,诱导组神经元烯醇化酶阳性细胞率显著高于对照组(P<0.01);诱导组神经丝蛋白阳性细胞率为(44.2±2.4)%,对照组为阴性;两组胶质纤维酸性蛋白均呈阴性表达。结论:鼠脑C6胶质瘤细胞上清液可成功诱导人骨髓间充质干细胞向神经元样细胞分化。     

成人骨髓间充质干细胞体外诱导分化为胰岛素分泌样细胞及其鉴定

背景:体外诱导人骨髓间充质干细胞定向分化为胰岛样细胞,目前尚无成熟的鉴定方案.转基因诱导要求条件高,程序复杂,化学诱导剂诱导为现阶段较多采用的一类方法.目的:探讨成人骨髓间充质干细胞体外诱导分化为胰岛样细胞的条件.设计、时间及地点:细胞学体外观察,于2007-01/10在青岛大学医学院附属医院中心实验室完成.材料:骨髓来源于青岛大学医学院附属医院内分泌科行自体干细胞移植治疗的糖尿病患者,对治疗及实验均签署知情同意书.表皮细胞生长因子、碱性成纤维细胞生长因子为Peprotech Asia公司产品,B27添加剂为Gibco公司产品,尼克酰胺、2-巯基乙醇、谷氨酰胺、双硫踪为Sigma公司产品.方法:采用Percoll法分离成人骨髓间充质干细胞,加入含体积分数为0.1胎牛血清的LG-DMEM进行培养,胰蛋白酶消化传代.取第3～5代细胞,按1×108 L-1密度接种,分3阶段诱导:第1阶段加入含2-巯基乙醇、谷氨酰胺的HG-DMEM,培养2 d;第2阶段加入含碱性成纤维细胞生长因子、表皮生长因子、B27添加剂、谷氨酰胺的HG-DMEM,培养6 d;第3阶段加入含尼克酰胺、2-巯基乙醇的HG-DMEM,培养6 d.对照组采用单纯的HG-DMEM进行培养.主要观察指标:相差显微镜下观察细胞形态变化,诱导第2阶段行免疫荧光鉴定PDX-1基因的表达,诱导第3阶段行双硫腙染色鉴定胰岛β样细胞团,电化学发光法测定低糖/高糖刺激下胰岛素的分泌情况.结果:未经诱导的骨髓间充质干细胞呈长梭形贴壁生长,诱导后胞逐渐变圆,并聚集成团.诱导8 d细胞PDX-1基因呈阳性表达,诱导14 d细胞团双硫腙染色呈棕红色.经低糖、高糖刺激后,对照组无胰岛素释放,诱导14 d细胞团培养基中胰岛素含量显著升高(t=3.638～9.387,P均 < 0.01).结论:2-巯基乙醇、谷氨酰胺、表皮生长因子、碱性成纤维细胞生长因子及尼克酰胺等可在体外诱导成人骨髓间充质干细胞分化为具有分泌胰岛素功能的胰岛样细胞.     

胰岛素,C肽释放试验对糖尿病临床分型的研究

采用进食１００ｇ标准面粉馒头餐方法对正常人，胰岛纱依赖型尿病，非胰岛素依赖型糖尿病，葡萄糖耐异常患者进行胰岛素，Ｃ肽动态观察。结果表明：（１）ＩＤＤＭ患者ＩＮＳ，ＣＰＲ分泌显著低于对照组，呈绝对不足；（２）ＮＩＤＤＭ患者ＩＮＳ，ＣＰＲ达峰时间明显落后于对照组，显示出ＮＩＤＤＭ的重要特征；（３）ＮＩＤＤＭ患者ＩＮＳ，ＣＰＲ达峰值时间明显落后于对照组，显示出ＮＩＤＤＭ的重要特征；（３）ＩＧＴ患者达峰值     

表面活性剂和全氟三丁胺对可移植海藻酸钠/聚赖氨酸/海藻酸钠微胶囊性能的影响

实验以球磨法测定海藻酸钠/聚赖氨酸/海藻酸钠微胶囊的破碎率,并用激光共聚焦扫描显微镜观察绿色荧光标记的蛋白是否进入微胶囊,考察了加入表面活性剂F68和全氟三丁胺对不同直径微胶囊的机械强度、免疫隔离性能和通透性能的影响。通过对不同直径的海藻酸钠/聚赖氨酸/海藻酸钠微胶囊的破碎率的分析,基本确定了添加F68及全氟三丁胺的浓度对不同粒径微囊的机械强度产生了不同的协同影响。控制F68和全氟三丁胺的浓度配比及减小微囊的直径可以减小F68和全氟三丁胺对海藻酸钠/聚赖氨酸/海藻酸钠微胶囊的机械强度的影响。而表面活性剂和全氟三丁胺的加入基本不影响微胶囊的免疫隔离性能和通透性能。     

Prevention of morphological changes in alginate microcapsules for islet xenotransplantation.

BACKGROUND: Alginate microcapsule swelling, which occurs as a result of increased hydrophilicity owing to the Ca++ that remains after rapid chelation of the inner alginate core, is a problem in encapsulation. We have previously shown that exchange of the residual divalent Ca++ with the monovalent Na+ through the use of 6 mmol/L Na2SO4 decreases swelling in chelated alginate-polylysine-alginate microcapsules, and this process enhances their durability. The purpose of the present study was to examine the morphology of Na2SO4-treated microcapsules in long-term incubation with the use of serum-supplemented culture medium. METHODS: Spherical beads of purified alginate (3%) that were gelled with 1.1% CaCl2 were first coated with polylysine, and then with 0.24% alginate. After rapid chelation of the inner alginate core with 55 mmol/L sodium citrate, the capsules were either incubated for 30 minutes in 6 mmol/L Na2SO4 or left untreated (control). Each group of capsules was then placed in a flask containing Ham's culture medium supplemented with 20% porcine serum and incubated at 37 degrees C. RESULTS: The diameters of Na2SO4-treated capsules only increased modestly from a mean +/- SD of 635 +/- 22.08 to 684.53 +/- 17.86 microm (P<0.0001) by day 7, with no further increases thereafter. In contrast, control capsules showed a steady increase in their mean diameters, which changed from 639.55 +/- 21.44 to 735.48 +/- 108.85 microm (P < 0.0001) by day 66. In addition, whereas treated capsules remained spherical, control capsules showed progressive polymorphism. CONCLUSION: We have developed a new method of making more durable and stable microcapsules that can be used for islet cell xenotransplantation.     

Delivery of recombinant gene products to the central nervous system with nonautologous cells in alginate microcapsules

Somatic gene therapy using nonautologous recombinant cells immunologically protected with alginate microcapsules has been successfully used to treat rodent genetic diseases. We now report the delivery of recombinant gene products to the brain in rodents by implanting microencapsulated cells for the purpose of eventually treating neurodegenerative diseases with this technology. Alginate-poly-L-lysine-alginate microcapsules enclosing mouse C2C12 myoblasts expressing the marker gene human growth hormone (hGH) at 95+/-20 ng/million cells/hr were implanted into the right lateral ventricles of mice under stereotaxic guidance. Control mice were implanted similarly with nontransfected but encapsulated cells. Delivery of hGH to the different regions of the brain at various times postimplantation was examined. At 7, 28, 56, and 112 days postimplantation, hGH was detected at high levels around the implantation site and also at lower levels in the surrounding regions, while control mice showed no signal. Immunohistochemical staining of the implanted brains showed that on days 7, 56, and 112 postimplantation, hGH was localized in the tissues around the implantation site. Mice implanted with encapsulated but nontransfected cells showed no signal. Hence, the feasibility of using encapsulated nonautologous cells to deliver recombinant gene products to the brain for extended periods may allow the application of this technology to the treatment of neurodegenerative genetic disorders.     

The role of pathogen-associated molecular patterns in inflammatory responses against alginate based microcapsules

Alginate-based microcapsules are used for immunoisolation of cells to release therapeutics on a minute-to-minute basis. Unfortunately, alginate-based microcapsules are suffering from varying degrees of success, which is usually attributed to differences in tissue responses. This results in failure of the therapeutic cells. In the present study we show that commercial, crude alginates may contain pathogen-associated molecular patterns (PAMPs), which are recognized by the sensors of the innate immune system. Known sensors are Toll-like receptors (TLRs), NOD receptors, and C-type lectins. By using cell-lines with a non-functional adaptor molecule essential in Toll-like receptor signaling, i.e. MyD88, we were able to show that alginates signal mainly via MyD88. This was found for low-G, intermediate-G, and high-G alginates applied in calcium-beads, barium-beads as well as in alginate–PLL–alginate capsules. These alginates did stimulate TLRs 2, 5, 8, and 9 but not TLR4 (LPS receptor). Upon implantation in rats these alginates provoked a strong inflammatory response resulting in fibrosis of the capsules. Analysis demonstrated that commercial alginates contain the PAMPs peptidoglycan, lipoteichoic acid, and flagellin. By applying purification procedures, these PAMPs were largely removed. This was associated with deletion of the inflammatory tissue responses as confirmed by an implantation experiment in rats. Our data also show that alginate itself does not provoke TLR mediated responses. We were able to unravel the sensor mechanism by which contaminants in alginates may provoke inflammatory responses.     

糖尿病患者胰岛自身抗体测定与血清C肽水平的关系

目的研究胰岛自身抗体与胰岛β细胞功能的关系.方法测定302例住院的糖尿病(DM)患者的血清C肽、胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体GADA)的水平.并按病程的长短、抗体的阳性进行分组分析.结果46例速发型1型DM中,21.7%呈现ICA阳性,39.1%呈现GADA阳性.在临床初诊为2型DM的256例患者中,18.7%有一种以上抗体阳性,其中4.7%呈现ICA阳性,15.6%呈现GADA阳性.并且随着病程的延长,患者均有空腹和餐后2hC肽水平的下降,下降速度以1型DM最快,LADA次之,2型DM最慢.结论GADA和ICA联合测定有助于诊断LADA,而且LADA患者β细胞功能衰退较慢,保护残存β细胞有利于延缓病情发展.     

Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance

OBJECTIVE: We studied the relationships between plasma IGF-I concentrations and insulin sensitivity in subjects with various degrees of glucose tolerance. RESEARCH DESIGN AND METHODS: A total of 357 nondiabetic subjects, 54 subjects with impaired glucose tolerance and 98 newly diagnosed type 2 diabetic subjects, were consecutively recruited, and anthropometric and biochemical characteristics were collected. RESULTS: IGF-I concentrations were negatively correlated with age, BMI, waist-to-hip ratio, triglyceride levels, and systolic and diastolic blood pressure. IGF-I concentrations were positively correlated with HDL cholesterol and homeostasis model assessment of insulin sensitivity (HOMA-S). The correlations remained significant after adjusting for sex, age, and BMI. Correlations for HOMA-S with these metabolic and anthropometric variables were of a similar degree and direction to those for IGF-I concentrations. Stepwise linear regression analysis in a model, which included well-known modulators of insulin sensitivity such as sex, age, BMI, glucose tolerance status, family history of diabetes, waist-to-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, and triglyceride levels, revealed that IGF-I concentrations were independently associated with insulin sensitivity accounting for 10.8% of its variation (P < 0.0001). IGF-I concentrations were significantly lower in subjects with World Health Organization (WHO)-defined metabolic syndrome compared with subjects without metabolic syndrome (P < 0.0001). Logistic regression analysis showed that each unit increase in log-transformed IGF-I concentrations was associated with a 90.5% reduction in the risk of WHO-defined metabolic syndrome. CONCLUSIONS: These data indicate that IGF-I has the characteristics to be a marker for the insulin resistance syndrome. This suggests that low IGF-I levels may be a useful marker for identifying subjects at risk for cardiovascular disease.     

多肽及蛋白类药物微囊制剂研究的特点

学术背景：多肽及蛋白类药物稳定性差、易被酶降解，口服给药的生物利用低，如将其包埋成微囊制剂，不仅能有效防止药物在体内很快被降解，还能够提高药物的稳定性，实现缓释或控释。目的；介绍几种常用的多肽及蛋白类药物微囊制备方法，并比较各种方法的优缺点，以及常用的药用辅料。检索策略；由第一、二作者应用计算机检索Proquest和Elsevier数据库1993—01／2008—01文献，检索词为“microcapsule”，限定语言种类为“English”：同时检索维普中文期刊数据库、万方数据库1996-01／2008-01文献，检索词为“微囊”，限定语言种类为中文。纳入与多肽及蛋白类药物微囊制备方法、工艺优化及壁材选择有关文献，排除较陈旧的文献及重复研究。文献评价；共收集到140篇相关文献，30篇符合标准，其中22篇介绍多肽及蛋白类药物微囊制备方法，8篇关于常用的药用辅料。资料综合；①多肽及蛋白类药物微囊化的常用制备方法主要有复相乳液法、超临界流体法、喷雾干燥法，具体制备过程中应根据药物的理化性质选择合适的方法。②用于制备多肽或蛋白类药物的壁材主要有可生物降解聚合物和生物黏附材料。结论；多肽及蛋白类药物微囊制备应根据其不同的理化性质选择合适的制备方法和壁材，以获得最理想的实验结果。同时，多肽及蛋白质类药物的稳定性将是制备过程中需要重点考察的内容。