纤维化胶原蛋白海绵的制备及其自组装工艺

背景：传统的胶原蛋白海绵支架降解速度过快,机械强度低,在应用过程中容易塌陷,很难维持其固有形态,不能满足长期执行细胞支架功能的需要,常见的交联方式又存在细胞毒性或胶原蛋白变性等缺陷。目的：设计一种新的交联工艺,并对工艺条件进行优化,制备出力学性能和耐降解性能良好的胶原蛋白海绵支架材料。方法：通过体外自组装技术对胶原蛋白进行改性处理,制备具有丝状结构的胶原蛋白纤维,采用单因素分析考察初始胶原蛋白质量浓度、磷酸盐终浓度及pH值对胶原蛋白自组装转化率的影响;根据单因素实验结果,采用正交实验得到最佳胶原蛋白自组装工艺条件。将最佳工艺条件制备的胶原蛋白溶液与未进行改性处理的胶原蛋白溶液冷冻干燥得到胶原蛋白海绵,并进行表征。结果与结论：胶原蛋白体外自组装的最佳工艺为：初始胶原蛋白质量浓度为2 g/L,pH=8,磷酸盐终浓度为15 mmol/L,此时自组装转化率最大。扫描电镜显示改性处理胶原蛋白海绵具有纤维丝构成的网状结构,其溶胀率、保水率、机械强度均高于未改性处理胶原蛋白海绵(P < 0.05),克服了未改性处理胶原蛋白海绵降解过快的缺陷。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

胶原蛋白海绵对肝脏创伤止血的效果北大核心

背景:艾瑞金胶原蛋白海绵理化性能稳定,并已通过国家食品药品监督管理局的理化性能和生物相容性评价检测。目的:观察艾瑞金胶原蛋白海绵的止血效果。方法:取21只SD大鼠,建立肝脏出血创面,随机分3组干预:在实验组(n=7)肝脏创口内部植入艾瑞金胶原蛋白海绵,同时在肝脏切口表面外敷艾瑞金胶原蛋白海绵;在阳性对照组(n=7)肝脏创口内部植入医用胶原蛋白海绵,同时在肝脏切口表面外敷医用金胶原蛋白海绵;在空白对照组(n=7)肝脏切口表面外敷医用纱布,记录出血量及止血时间,干预后7,14,28 d进行肝脏创面组织学观察。结果与结论:①出血量及止血时间:3组出血量比较无差异;实验组、阳性对照组止血时间与空白对照组比较差异无显著性意义,实验组止血时间短于阳性对照组(P≤0.05);②肝脏创面组织学观察:实验组干预后7 d胶原材料被纤维结缔组织完全包裹,炎性细胞浸润以中性粒细胞为主,胶原材料开始降解,周边结缔组织内有新生毛细血管;干预后14 d,包裹胶原材料的纤维结缔组织明显增厚,中性粒细胞减少,巨噬细胞增多;干预后28 d,胶原材料完全降解,大部肝组织恢复正常,部分肝组织旁的炎性结缔组织中可看到巨噬细胞、单核细胞、成纤维细胞和毛细血管。阳性对照组情况类似于实验组。空白对照组干预后14 d创伤处结缔组织明显,肝窦含有红细胞,偶见肝组织内出血,空泡变性;干预后28 d,创口处具有较厚结缔组织,肝窦含有红细胞,被复肝星状细胞;③结果表明:艾瑞金胶原蛋白海绵对肝脏创伤止血效果明显,组织相容性好。     

胶原蛋白海绵的性质及其临床应用

背景:胶原蛋白海绵具有良好的功能和特性,及其易于加工、灭菌和保存等独特的优势,被视为最有用途的生物材料,具有广泛的科研和临床应用价值。 目的：介绍胶原蛋白海绵的性质,对近年来胶原蛋白海绵在临床应用上的研究成果进行综述。 方法：由第一作者应用计算机检索2000-01/ 2010-08 Pubmed数据库和Elsevier数据库,在标题和摘要中以 “collagen, collagen sponge, clinical application”为检索词进行检索。检索1993-01/2010-08 CNKI数据库,在标题和摘要中以“胶原,胶原蛋白海绵,临床应用”为检索词进行检索。纳入38篇文献进行综合分析。 结果与结论：胶原蛋白海绵作为一种新型生物材料,越来越广泛地被应用于止血、创面愈合、抗感染、软骨修复、神经修复等相关方面的组织工程与临床研究。但目前所使用的胶原几乎都是来源于动物,无法彻底消除免疫原性。 国外已有人利用生物反应器和转基因技术合成了重组人胶原,其在临床应用上的有效性和安全性等问题仍有待进一步的探索和研究。     

猪小肠黏膜下基质海绵的制备

 BACKGROUND: Studies have found that small intestinal submucosa that is directly implanted into the lesion cannot effectively promote cell growth and differentiation in vivo and in vitro, because of its small pore size and poor permeability.     

明胶海绵在腭裂修复中的应用北大核心

背景:在腭裂修复手术中,以往多采用碘仿纱条来填塞腭裂术后两侧松驰切口及覆盖创面。临床中作者发现,采用这种方法处理的患者,术后常出现发热、食欲不振、异物感、继发性出血等并发症。为避免或减少腭裂患者术后出现以上并发症,使用明胶海绵填塞双侧松弛切口,取得了良好的临床效果。目的:对比腭裂患者修复术中创面不同处理方法对伤口愈合效果的影响。方法:根据患儿入院时间,将110例腭裂手术患儿分为2组:2013年1月至2015年12月入院腭裂患儿54例为实验组,2008年1月至2012年12月入院腭裂患儿56例为对照组。实验组采用明胶海绵填塞创面,对照组应用碘仿纱包及碘仿纱条填塞创面,评估患儿术后精神、饮食、体温、创口出血及愈合等情况。术后4周复查,测量患者松弛切口处瘢痕条索宽度。结果与结论:(1)实验组精神、饮食恢复时间和出院时间短于对照组(P<0.05);(2)实验组发热率明显低于对照组(P<0.05),且发热时间短于对照组(P<0.05);(3)实验组术后出血、恶心呕吐发生率明显低于对照组,差异有显著性意义(P<0.05);(4)术后4周,实验组患儿松弛切口处瘢痕条索宽度明显窄于对照组,差异有显著性意义(P<0.05);(5)结果表明,明胶海绵止血可靠,术后反应轻,伤口愈合快,不影响进食,具有较好的临床应用价值。     

胶原蛋白海绵的制备及安全性评价

背景:自动物体提取胶原蛋白并经冻干工艺得到胶原蛋白海绵,可赋予材料良好的临床止血性能,同时可实现在机体中的自身降解,但所提取的胶原蛋白也存在携带病毒及体内免疫原性风险。经过酸酶结合工艺处理去除胶原端肽、并灭活病毒,实现材料良好的生物安全性。目的:规模化生产制备胶原蛋白海绵,并对其进行免疫原性及病毒灭活有效性的整体生物安全性评价。方法:通过酸酶结合法从牛跟腱中提取胶原蛋白,经冷冻干燥工艺得到胶原蛋白止血海绵。将1,4片胶原蛋白海绵分别埋植于Wistar大鼠腹部皮下,埋植1,4,8,12周后对大鼠体征、血常规、T淋巴细胞增殖、免疫球蛋白含量等指标进行检测。取3批次的牛跟腱粉碎后中间体样品,分别浸泡于伪狂犬病毒、水泡性口炎病毒、猪细小病毒和猪脑心肌炎病毒液中,检验酸酶结合法处理的胶原蛋白海绵对病毒灭活的有效性。结果与结论:(1)于无菌车间规模化提取胶原蛋白,经冷冻干燥后得到胶原蛋白海绵,并完成内外包装和辐照灭菌的生产全过程;(2)埋植1,4片胶原蛋白海绵大鼠的生理体征、血常规、NK细胞杀伤活性、T淋巴细胞增殖状态及免疫球蛋白含量等指标均表现正常;(3)酸酶法工艺灭活的3批次牛跟腱粉碎后中间体...     

医用胶原蛋白海绵及负压封闭引流联合自体刃厚皮复合移植在足部毁损伤难愈性创面中的应用

目的观察医用胶原蛋白海绵及负压封闭引流(VSD)联合自体刃厚皮复合移植修复足部毁损伤难愈性创面的效果。方法选取2017年1月至2019年10月海南省人民医院烧伤与皮肤修复外科收治的足部毁损伤难愈性创面患者18例,其中合并足背肌腱外露12例,跖骨骨外露6例。创面清创后,予医用胶原蛋白海绵覆盖肌腱外露、骨外露创面,并安装VSD装置,待创面覆盖肉芽组织后,再给予自体刃厚皮移植修复创面。记录治疗时间、外露肌腱或骨质坏死率、皮片成活率,术后随访6个月,以Maryland足部功能评分标准评估外观及功能。结果18例患者足部均得以保存,外露的肌腱和骨质均保持活性,皮片成活率85%~95%,平均(90±5)%。残余创面给予间断换药治疗后全部愈合,治疗时长14.0~45.0 d,平均(29.5±15.5)d。出院后6个月复诊以Maryland足部功能评分标准评估足部功能,优3例,良4例,中6例,差5例。结论医用胶原蛋白海绵及VSD在促进肌腱、骨质外露创面肉芽组织生长的同时可保留外露的肌腱及骨组织活性,联合自体刃厚皮移植,能较好地修复足部毁损伤难愈性创面。     

酸性成纤维细胞生长因子/胶原蛋白复合海绵的研制及其组织相容性

我们以牛跟腱和酸性成纤维细胞生长因子(acidic fibroblast growth factor,aFGF)为原料,研制了一种新型的创伤敷料--aFGF/胶原蛋白复合海绵,并检测了其物理性能和组织相容性,特别是在血液相容性方面,研究其作为医用生物材料的安全性.结果显示:制备的高剂量和低剂量aFGF/胶原蛋白复合海绵的急性毒性试验、刺激性试验结果均为阴性;复钙试验表明aFGF/胶原蛋白复合海绵复钙时间较长,具有较好的抗凝特性;溶血试验表明复合海绵对红细胞的破坏很小,符合生物材料的溶血性要求;血小板黏附试验表明aFGF/胶原蛋白复合海绵的血小板黏附量较少且未被激活,对血小板没有明显的破坏作用.结果表明,aFGF/胶原蛋白复合海绵具有较好的组织相容性,具备临床应用的可能性.     

胶原蛋白-硫酸肝素生物支架在猪脑内的生物相容性分析

背景：胶原蛋白-硫酸肝素支架与人体神经内部结构十分相似。 目的：探讨胶原蛋白-硫酸肝素支架的体内生物相容性。 方法：将40只小猪随机均分为两组,以距离前囟中线旁开1.0 cm为穿刺点,利用骨穿针进行纵向穿刺,至脑蛛网膜下腔,感到落空感后,将骨穿针缓慢拔除,观察组植入胶原蛋白-硫酸肝素支架,对照组不予处置。术后1,3,7,14,30 d对两组脑组织进行透射电镜观察、细胞凋亡及Caspase-3蛋白表达检测。 结果与结论：早期电镜观察发现,观察组支架周边有个别脑组织神经元受损情况,并出现髓神经纤维脱髓鞘变化,支架与脑组织交界处及支架内部存在阳性Caspase-3蛋白,但在远离支架周边脑组织则无阳性蛋白表达。从术后1 d开始,观察组支架周边脑组织出现个别脑细胞凋亡情况,至术后30 d无明显凋亡细胞,对照组也表现出相似的变化,观察组术后1,3,7,14 d细胞凋亡数量高于对照组(P < 0.05),两组术后 30 d细胞凋亡数量比较差异无显著性意义(P > 0.05)。两组Caspase-3蛋白表达均处于较低状态,且观察组术后3,7 d的Caspase-3蛋白表达高于对照组(P < 0.05),其余时间点比较差异无显著性意义。表明胶原蛋白-硫酸肝素支架在猪脑内具有良好的生物相容性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

局部应用明胶海绵浸润鼠神经生长因子治疗周围神经损伤

背景：有研究尝试将外源性鼠神经生长因子用于周围神经损伤局部,发现局部注射鼠神经生长因子能有效促进损伤神经修复,且局部应用效果优于全身应用。目的：评价明胶海绵浸润鼠神经生长因子用于治疗周围神经损伤的临床疗效。方法：纳入单一、完全断裂周围神经损伤患者36例,其中男16例,女20例,年龄18-48岁,采用随机数字表法均分为2 组,实验组急诊行清创、神经端端直接吻合,术中将浸润鼠神经生长因子的明胶海绵环绕包裹于神经吻合处;对照组急诊行清创、神经端端直接吻合,吻合神经处不予特殊处理。两组术后常规石膏固定,抗炎、营养神经、改善循环治疗。治疗后4周进行电生理检查,治疗后6个月进行神经损伤远端感觉、运动功能评价。结果与结论：实验组感觉电位恢复14例,恢复率为78%;运动电位恢复15例,恢复率为83%。对照组感觉电位恢复10例,恢复率为57%;运动电位恢复12例,恢复率为66%。两组间感觉、运动电位恢复率比较差异有显著性意义(P < 0.05)。实验组17例神经功能得到不同程度恢复,总有效率为94%;对照组15例神经功能得到不同程度恢复,总有效率为83%,两组间总有效率比较差异有显著性意义(P < 0.05)。表明局部应用明胶海绵浸润鼠神经生长因子可有效促进周围神经损伤的修复,且具有良好的生物相容性。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

京尼平交联仿骨结构诱导性骨组织工程支架材料的制备与表征

 背景：目前,尽管利用各种材料制备的组织工程化骨研究取得了一定进展,但均表现出诸如支架材料降解速度与新生骨组织形成速率不匹配、组织生长缓慢、降解代谢产物有毒性等缺陷。目的：构建一种新型的仿骨结构诱导性骨组织工程支架材料,评价其物理化学及生物学性能。方法：以壳聚糖包被淫羊藿苷制备微球,检测其体外缓释效果;将载药微球与胶原蛋白复合构建支架材料的管芯;将羟基磷灰石、聚己内酯与胶原蛋白依次以0∶3∶3、1∶3∶3、2∶3∶3、3∶3∶3的比例混合于六氟异丙醇中,通过静电纺丝技术依次电纺制得具有4层结构的支架材料外管;以1%京尼平将经嵌套的管芯与外管交联在一起。利用万能材料试验机、表面接触角仪、红外光谱、扫描电镜、吸水率、透气性、孔隙率、体外降解实验等对交联前后外管材料的结构和特征进行表征,并评价骨髓间充质干细胞与外管材料的生物相容性;Wistar大鼠皮下埋置实验进一步评价交联前后外管材料的组织相容性。结果与结论：药物在管芯中具有良好的缓释效果;制备的骨组织工程支架材料具有良好的均一性,交联后外管材料的力学性能、吸水率、透气性均高于未交联组(P < 0.05),且体外降解速率显著低于未交联组(P < 0.05)。苏木精-伊红染色显示骨髓间充质干细胞可良好贴附于交联前后的外管材料上;交联的外管材料植入Wistar大鼠皮下后均无炎症反应。表明交联后诱导性骨组织工程支架材料具有良好的生物相容性及力学性能。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Crosslinked collagen hydrogels as corneal implants: Effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers

We have previously shown that recombinant human collagen can be crosslinked with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) to fabricate transparent hydrogels possessing the shape and dimensions of the human cornea. These corneal implants have been tested in a Phase I human clinical study. Although these hydrogels successfully promoted corneal tissue and nerve regeneration, the gelling kinetics were difficult to control during the manufacture of the implants. An alternative carbodiimide capable of producing hydrogels of similar characteristics as EDC in terms of strength and biocompatibility, but with a longer gelation time would be a desirable alternative. Here, we compared the crosslinking kinetics and properties of hydrogels crosslinked with a sterically bulky carbodiimide, N-Cyclohexyl-N′-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (CMC), with that of EDC. CMC crosslinking was possible at ambient temperature whereas the EDC reaction was too rapid to control and had to be carried out at low temperatures. The highest tensile strength obtained using optimized formulations were equivalent, although CMC crosslinked hydrogels were found to be stiffer. The collagenase resistance of CMC crosslinked hydrogels was superior to that of EDC crosslinked hydrogels while biocompatibility was similar. We are also able to substitute porcine collagen with recombinant human collagen and show that the in vivo performance of both resulting hydrogels as full-thickness corneal implants is comparable in a mouse model of an orthotopic corneal graft. In conclusion, CMC is a viable alternative to EDC as a crosslinker for collagen-based biomaterials for use as corneal implants, and potentially for use in other tissue engineering applications.     

Crosslinking of collagen with dendrimers

Polypropyleneimine octaamine dendrimers were studied as an alternative means of generating highly crosslinked collagen. Crosslinking was effected by using the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC). The multifunctional dendrimers were introduced as novel crosslinkers after the activation of the carboxylic acid groups of glutamic and aspartic acid residues in collagen. The conventional crosslinker glutaraldehyde was used as a control. EDC, itself an alternative crosslinker, which forms zero-length crosslinks by directly covalently binding collagen molecules, as well as a low molecular weight diamine and a low molecular weight triamine, were also studied. All of the resultant gels were freeze-dried to obtain sponges for characterization. Water uptake of the gels decreased from 90% to 60% after dendrimer crosslinking compared with EDC crosslinking. DSC results showed an increase of denaturation temperature of collagen after crosslinking with the various methods. The generation 2 and 3 dendrimer-crosslinked collagen samples had the highest denaturation temperature, at up to 90 degrees C compared with 50 degrees C in the uncrosslinked collagen control. The dendrimer-crosslinked collagen also showed unique thermal characteristics, with multiple denaturation temperature peaks in contrast to the single peak noted with the other crosslinked collagens. This is thought to be due to the heterogeneous nature of dendrimer crosslinking. Collagenase results revealed that the dendrimer-crosslinked collagen had a comparative resistance to proteolysis to glutaraldehyde-crosslinked collagen. Measurement of activated carboxylic acid groups before and after crosslinking indicated that 40-70% of the activated carboxylic acid was consumed during crosslinking with dendrimers. The results suggest that dendrimer crosslinking of collagen produces stable gels. The presence of a large number of excess amine groups in the dendrimers may also be useful for subsequent modification with biologically relevant groups.     

Crosslinking of collagen gels by transglutaminase

Collagen is commonly used as a tissue-engineering scaffold, yet its in vivo applications are limited by a deficiency in mechanical strength. The purpose of this work was to explore the utilization of a unique enzymatic crosslinking procedure aimed at improving the mechanical properties of collagen-based scaffold materials. Type I bovine collagen gel was crosslinked by transglutaminase, which selectively mediates the chemical reaction between glutamine and lysine residues on adjacent protein fibers, thus providing covalent amide bonds that serve to reinforce the three-dimensional matrix. The degree of crosslinking was verified by thermal analysis and amine group content. The denaturation temperature of crosslinked collagen reached a maximum of 66 +/- 1 degrees C. The chemical reaction was confirmed to be noncytotoxic with respect to bone marrow stromal cells acquired from New Zealand White rabbits. Tube-shaped cellular constructs fashioned from crosslinked collagen and bone marrow stromal cells were found to have burst pressures significantly higher than their noncrosslinked analogs (71 +/- 4 mmHg vs. 46 +/- 3 mmHg; p < 0.01). Thus, the transglutaminase mediated reaction served to successfully strengthen collagen gels while remaining benign toward cells.     

羊膜上皮细胞胶原海绵复合体促大鼠预构皮瓣成活及其再血管化

目的　移植羊膜上皮细胞(AECs) 胶原海绵复合体促进预构皮瓣成活。 方法　第3代SD大鼠AECs、软骨细胞株分别植于胶原蛋白海绵支架,并提取AECs组上清液行促血管形成因子VEGF、TGFβ1、bFGF的ELISA检测。SD大鼠分正常对照组、空白对照组、软骨细胞组和AECs组。一期手术后第7、14 d取皮瓣组织行促血管形成因子的ELISA检测。二期手术后第7 d用计算机图像分析系统测定皮瓣存活率,取存活部位组织行HE染色、vWF免疫组织化学染色以分析微血管密度。 结果　AECs复合体上清液中的促血管形成因子分泌逐渐增多;组织内各因子含量以AECs组最高,AECs组皮瓣存活率明显高于空白对照组和软骨细胞组。AECs组皮肤微血管面积比、vWF因子阳性区面积比明显高于其他组。 结论　植入AECs胶原海绵复合体可促进预构皮瓣的存活,与其分泌的一些促血管形成因子促进预构皮瓣再血管化有关。     

Acceleration of bone formation with BMP2 in frame-reinforced carbonate apatite–collagen sponge scaffolds

The development is expected of scaffold biomaterials that feature a shape-maintaining property in addition to high porosity and large pores that cells can easily invade. To develop a new biodegradable scaffold biomaterial reinforced with a frame, synthesized carbonate apatite (CO₃Ap) was mixed with neutralized collagen gel, and the CO₃Ap–collagen mixtures were lyophilized into sponges in a porous hydroxyapatite (HAp) frame ring. X-ray diffraction and Fourier transform infrared spectroscopy (FT-IR) analyses together with chemical analysis indicated that the synthesized CO₃Ap had a crystalline nature and a chemical composition similar to that of bone. Scanning electron microscope (SEM) observation showed that the CO₃Ap–collagen sponge had a sui pore size for cell invasion. In proliferation and differentiation experiments with osteoblasts, alkaline phosphatase and osteopontin activity were clearly detected. When these sponge–frame complexes with bone morphogenic protein (rh-BMP2) were implanted beneath the periosteum cranii of rats, significant new bone was created at the surface of the periosteum cranii after 4 weeks of implantation. These reinforced CO₃Ap–collagen sponges with rh-BMP2 are expected to be used as hard tissue scaffold biomaterials for the therapeutic purpose of the rapid cure of bone defects.     

Expression Analysis of Recombinant Lysyl Oxidase (LOX) in Myofibroblastlike Cells

Lysyl oxidase (LOX), originally known as the enzyme required for initiation of covalent cross-linking in collagens and elastin, is now known to be a member of a family of genetically related proteins. LOX, or a related protein, has also been localized intracellularly, both in association with the cytoskeleton and in the cell nucleus. To determine the structural requirements for secretion, maturation, and nuclear location of LOX in a cellular context, we have devised an homologous cell model for expression of the recombinant protein. Murine recombinant LOX was expressed in 3T6-5 myofibroblast-like cells as a 51-kD precursor, which was observed in the cytoplasm but not in the nucleus. To investigate whether potential alternative translation initiation sites were involved in specifying a nuclear form of LOX, constructs mutated or deleted for ATG +1 were used, but alternative initiation at CTG &#109 315 or ATG +418 did not lead to the expression of intranuclear forms. Residues 23 to 157 of the proregion were essential for export of the precursor, while mutation of the putative site for maturation by procollagen C-proteinase abolished processing to the mature form of the enzyme. Cross-linking of collagen, as measured by pyridinoline analysis, increased twofold with the recombinant cells, compared to non-transfected controls. This shows the specific contribution of LOX, as opposed to other genetic forms of the enzyme, to cross-linking in a cellular context.     

瘦素及I和III型胶原蛋白在肝纤维化大鼠肝组织中的变化

 摘要： 目的 研究瘦素（Leptin）及I、 III型胶原蛋白及基因在肝纤维化模型组织中的动态表达水平。方法 四氯化碳（CCl4）皮下注射法制备肝纤维化模型,分别以Western blot及RT-PCR法检测Leptin及I、 III型胶原蛋白及基因在肝纤维化组织中的动态表达。结果 Leptin以及I、 III型胶原蛋白及基因在正常对照组肝脏中均有微量表达,CCl4注射2周后,三者的表达均开始增强,随着纤维化发展呈梯度增加。其mRNA表达水平在模型组明显高于正常组 (P<0.05);在肝纤维化过程中,Leptin与I型胶原(r=0.595,P=0.017)及Leptin与III型胶原(r=0.478,P=0.011) 的动态改变呈显著正相关。结论 Leptin的表达随着纤维化的程度加重而逐步增强,在肝纤维化过程中,Leptin可能参与了细胞外基质成分（ECM）的合成与降解。