Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on human skin fibroblasts and HaCaT cells
-
摘要:
目的 探讨基于聚乙烯醇-硼酸（PVA-BA）的功能化水凝胶对人皮肤成纤维细胞（HSF）和HaCaT细胞的作用,为后续该水凝胶系统应用于创面修复的体内研究及临床转化提供实验依据。 方法 该研究为成组设计与析因设计实验研究。基于PVA-BA,采用冻融循环法制备PVA-BA水凝胶、负载终物质的量浓度为5 μmol/L SB431542的PVA-BA-S水凝胶、负载终物质的量浓度为1 μmol/L BML-284的PVA-BA-B水凝胶,分别采用傅里叶变换红外光谱仪、X射线衍射仪对前述水凝胶的特征吸收峰、衍射峰进行表征。利用液相色谱仪检测PVA-BA-S水凝胶和PVA-BA-B水凝胶各自在pH值为5.5和7.4的磷酸盐缓冲液（PBS）中的释放情况,计算浸泡48 h时的药物累计释放率。采用随机数字表法将HSF分为常规培养的对照组、经重组人转化生长因子-β1（TGF-β1）蛋白处理24 h后常规培养的单纯激活组,以及经重组人TGF-β1蛋白处理24 h后分别用PVA-BA水凝胶浸提液、PVA-BA-S水凝胶浸提液培养的PVA-BA组、PVA-BA-S组。培养24 h后,采用实时荧光定量反转录PCR法检测HSF中TGF-β通路相关因子α-平滑肌肌动蛋白（α-SMA）、TGF-β、Smad2、Smad3、Ⅰ型胶原蛋白（COLⅠ）、COLⅢ的mRNA表达水平,采用免疫荧光法检测HSF中COLⅠ、COLⅢ的蛋白表达水平。采用随机数字表法将HaCaT细胞分为常规培养的对照组、用PVA-BA水凝胶浸提液培养PVA-BA组及用PVA-BA-B水凝胶浸提液培养的PVA-BA-B组,培养24 h后,采用实时荧光定量反转录PCR法检测细胞中Wnt通路相关因子β-连环蛋白、基质金属蛋白酶9（MMP-9）、E-钙黏蛋白、N-钙黏蛋白的mRNA表达水平,采用免疫荧光法检测细胞中角蛋白5的蛋白表达水平。除表征外,以上实验样本数均为3。 结果 PVA-BA水凝胶、PVA-BA-S水凝胶、PVA-BA-B水凝胶的傅里叶变换红外光谱均在波数1 100、1 450 cm-1处表现出B-O-C中C-O和B-O的伸缩振动峰,X射线衍射图谱在20°左右均形成一个尖锐的衍射峰。浸泡48 h时,PVA-BA-S水凝胶在pH值为5.5的PBS中的药物累计释放率为（70.9±2.3）%,显著高于在pH值为7.4的PBS中的（60.0±2.2）%（t=6.02,P<0.05）；PVA-BA-B水凝胶在pH值为5.5的PBS中的药物累计释放率为（83.9±2.2）%,显著高于在pH值为7.4的PBS中的（65.2±1.7）%（t=11.63,P<0.05）。培养24 h后,PVA-BA-S组HSF中TGF-β、COLⅠ、COLⅢ、Smad3的mRNA表达水平均显著高于对照组（P<0.05）,TGF-β、COLⅠ、COLⅢ、α-SMA、Smad2、Smad3的mRNA表达水平均显著低于单纯激活组及PVA-BA组（P<0.05）；PVA-BA-S组HSF中COLⅠ、COLⅢ的蛋白表达水平均显著低于单纯激活组和PVA-BA组（P<0.05）。培养24 h后,与对照组与PVA-BA组比较,PVA-BA-B组HaCaT细胞中β-连环蛋白、MMP-9、N-钙黏蛋白的mRNA表达水平均显著升高（P<0.05）,E-钙黏蛋白的mRNA表达水平显著降低（P值均<0.05）；PVA-BA-B组HaCaT细胞中角蛋白5的蛋白表达水平显著高于对照组与PVA-BA组（P值均<0.05）。 结论 基于PVA-BA的PVA-BA-S水凝胶和PVA-BA-B水凝胶可分别通过调控TGF-β通路和Wnt通路有效抑制活化HSF的纤维化表型及增强HaCaT细胞迁移能力,为创面功能性愈合提供了一种新型药物递送策略。 Abstract:Objective To investigate the effects of polyvinyl alcohol-boric acid (PVA-BA)-based functionalized hydrogels on human skin fibroblasts (HSFs) and HaCaT cells, providing experimental evidences for subsequent in vivo studies on wound repair and clinical translation of this hydrogel system. Methods This study was designed as a grouped and factorial experimental investigation. Based on PVA-BA, a freeze-thaw cycling method was employed to prepare PVA-BA hydrogel, PVA-BA-S hydrogel loaded with a final molarity of 5 μmol/L SB431542, and PVA-BA-B hydrogel loaded with a final molarity of 1 μmol/L BML-284. Fourier transform infrared spectroscopy and X-ray diffraction were employed to characterize the characteristic absorption peaks and diffraction patterns of the above-mentioned hydrogels. The drug release of PVA-BA-S hydrogel and PVA-BA-B hydrogel in phosphate-buffered saline (PBS) with pH values of 5.5 and 7.4 was detected using a liquid chromatography, and the cumulative drug release rate at 48 hours of immersion was calculated. According to the random number table method, HSFs were divided into control group with conventional culture, activation-only group with conventional culture after treatment with recombinant human transforming growth factor-β1 (TGF-β1) protein for 24 hours, as well as PVA-BA group and PVA-BA-S group cultured with PVA-BA hydrogel extract and PVA-BA-S hydrogel extract, respectively, after treatment with recombinant human TGF-β1 protein for 24 hours. After 24 hours of culture, mRNA expression levels of TGF-β pathway-related factors α-smooth muscle actin (α-SMA), TGF-β, Smad2, Smad3, type Ⅰ collagen (COL Ⅰ), COL Ⅲ in HSFs were detected using real-time fluorescence quantitative reverse transcription polymerase chain reaction. Protein expression levels of COL Ⅰ and COL Ⅲ in HSFs were assessed via the immunofluorescence method. According to the random number table method, HaCaT cells were divided into control group with conventional culture, PVA-BA group cultured with PVA-BA hydrogel extract, and PVA-BA-B group cultured with PVA-BA-B hydrogel extract. After 24 hours of culture, mRNA expression levels of Wnt pathway-related factors β-catenin, matrix metalloproteinase-9 (MMP-9), E-cadherin, N-cadherin in HaCaT cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The protein expression level of keratin 5 was evaluated by the immunofluorescence method. Except for characterization, the sample size for each experiment was 3. Results The Fourier transform infrared spectroscopy spectra of the PVA-BA hydrogel, PVA-BA-S hydrogel, and PVA-BA-B hydrogel all exhibited stretching vibration peaks corresponding to C-O and B-O bonds within the B-O-C group at wavenumbers of 1 100 and 1 450 cm⁻¹, and X-ray diffraction patterns all showed a sharp diffraction peak at around 20°. At 48 hours of immersion, the cumulative drug release rate of PVA-BA-S hydrogel in PBS at pH 5.5 was (70.9±2.3)%, which was significantly higher than (60.0±2.2)% in PBS at pH 7.4 (t=6.02, P<0.05); the cumulative drug release rate of PVA-BA-B hydrogel in PBS at pH 5.5 was (83.9±2.2)%, which was significantly higher than (65.2±1.7)% in PBS at pH 7.4 (t=11.63, P<0.05). After 24 hours of culture, the mRNA expression levels of TGF-β, COL Ⅰ, COL Ⅲ, and Smad3 of HSFs in PVA-BA-S group were significantly higher than those in control group (P<0.05), the mRNA expression levels of TGF-β, COL Ⅰ, COL Ⅲ, α-SMA, Smad2, and Smad3 were significantly lower than those in activation-only group and PVA-BA group (P<0.05), and the protein expression levels of COL Ⅰ and COL Ⅲ of HSFs in PVA-BA-S group were significantly lower than those in activation-only group and PVA-BA group (P<0.05). After 24 hours of culture, compared with those in control group and PVA-BA group, the PVA-BA-B group showed significantly increased mRNA expression levels of β-catenin, MMP-9, and N-cadherin (P<0.05) and a significantly decreased mRNA expression level of E-cadherin (both P values <0.05) in HaCaT cells; the protein expression level of keratin 5 of HaCaT cells in PVA-BA-B group was significantly higher than that in control group and PVA-BA group (both P values <0.05). Conclusions PVA-BA-S hydrogel and PVA-BA-B hydrogel based on the PVA-BA can effectively inhibit the fibrotic phenotype of activated HSFs and enhance the migratory ability of HaCaT cells by regulating the TGF-β pathway and Wnt pathway, respectively, providing a novel drug delivery strategy for functional wound healing. -
Key words:
- Hydrogels /
- Polyvinyl alcohol /
- Boric acids /
- Fibroblasts /
- HaCaT Cells /
- Transforming growth factor-β pathway /
- Wnt pathway /
- pH-response
-
参考文献
(38) [1] PeñaOA,MartinP.Cellular and molecular mechanisms of skin wound healing[J].Nat Rev Mol Cell Biol,2024,25(8):599-616.DOI: 10.1038/s41580-024-00715-1. [2] TalbottHE,MascharakS,GriffinM,et al.Wound healing, fibroblast heterogeneity, and fibrosis[J].Cell Stem Cell,2022,29(8):1161-1180.DOI: 10.1016/j.stem.2022.07.006. [3] SarateRM,HochstetterJ,ValetM,et al.Dynamic regulation of tissue fluidity controls skin repair during wound healing[J].Cell,2024,187(19):5298-5315.e19.DOI: 10.1016/j.cell.2024.07.031. [4] RodriguesM,KosaricN,BonhamCA,et al.Wound healing: a cellular perspective[J].Physiol Rev,2019,99(1):665-706.DOI: 10.1152/physrev.00067.2017. [5] JeschkeMG,WoodFM,MiddelkoopE,et al.Scars[J].Nat Rev Dis Primers,2023,9(1):64.DOI: 10.1038/s41572-023-00474-x. [6] CoentroJQ,PuglieseE,HanleyG,et al.Current and upcoming therapies to modulate skin scarring and fibrosis[J].Adv Drug Deliv Rev,2019,146:37-59.DOI: 10.1016/j.addr.2018.08.009. [7] LinX,LaiY.Scarring skin: mechanisms and therapies[J].Int J Mol Sci,2024,25(3):1458.DOI: 10.3390/ijms25031458. [8] ShirakamiE,YamakawaS,HayashidaK.Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence[J/OL].Burns Trauma,2020,8:tkz003[2025-08-25].https://pubmed.ncbi.nlm.nih.gov/32341924/.DOI: 10.1093/burnst/tkz003. [9] Trinh-MinhT,ChenCW,Tran ManhC,et al.Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis[J].J Clin Invest,2024,134(10):e159884.DOI: 10.1172/JCI159884. [10] ZhangT,WangXF,WangZC,et al.Current potential therapeutic strategies targeting the TGF-β/Smad signaling pathway to attenuate keloid and hypertrophic scar formation[J].Biomed Pharmacother,2020,129:110287.DOI: 10.1016/j.biopha.2020.110287. [11] BurgyO,KönigshoffM.The WNT signaling pathways in wound healing and fibrosis[J].Matrix Biol,2018,68-69:67-80.DOI: 10.1016/j.matbio.2018.03.017. [12] YangB,LinY,HuangY,et al.Extracellular vesicles modulate key signalling pathways in refractory wound healing[J/OL].Burns Trauma,2023,11:tkad039[2025-08-25].https://pubmed.ncbi.nlm.nih.gov/38026441/.DOI: 10.1093/burnst/tkad039. [13] BaiR,GuoY,LiuW,et al.The roles of WNT signaling pathways in skin development and mechanical-stretch-induced skin regeneration[J].Biomolecules,2023,13(12):1702.DOI: 10.3390/biom13121702. [14] YangX,ZhangC,DengD,et al.Multiple stimuli-responsive MXene-based hydrogel as intelligent drug delivery carriers for deep chronic wound healing[J].Small,2022,18(5):e2104368.DOI: 10.1002/smll.202104368. [15] LiH,MengF,HuC,et al.Gradient solvent replacement-mediated formation of high-strength hydrogel-forming microneedle for long-term drug delivery[J].Adv Sci (Weinh),2025,12(30):e2500833.DOI: 10.1002/advs.202500833. [16] 顾雅男,徐翔昊,王彦平,等.氧化铈纳米酶-甲基丙烯酸酐化明胶水凝胶在小鼠全层皮肤缺损感染创面修复中的作用[J].中华烧伤与创面修复杂志,2024,40(2):131-140.DOI: 10.3760/cma.j.cn501225-20231120-00201. [17] 陈祎琦,周莹芊,魏茜,等.负载人脐带间充质干细胞来源的小细胞外囊泡的甲基丙烯酸酐化明胶水凝胶治疗小鼠全层皮肤缺损创面的效果[J].中华烧伤与创面修复杂志,2024,40(4):323-332.DOI: 10.3760/cma.j.cn501225-20231218-00248. [18] MaT,WuJ,ChenS,et al.pH-responsive modified HAMA microspheres regulate the inflammatory microenvironment of intervertebral discs[J].ACS Appl Mater Interfaces,2024,16(46):63295-63305.DOI: 10.1021/acsami.4c14475. [19] LiuY,LiuT,ZhuZ,et al.An advanced hydrogel dressing system with progressive delivery and layer-to-layer response for diabetic wound healing[J].Acta Biomater,2024,190:79-94.DOI: 10.1016/j.actbio.2024.10.046. [20] ZhangG,SongD,MaR,et al.Artificial mucus layer formed in response to ROS for the oral treatment of inflammatory bowel disease[J].Sci Adv,2024,10(30):eado8222.DOI: 10.1126/sciadv.ado8222. [21] SuM,RuanL,DongX,et al.Current state of knowledge on intelligent-response biological and other macromolecular hydrogels in biomedical engineering: a review[J].Int J Biol Macromol,2023,227:472-492.DOI: 10.1016/j.ijbiomac.2022.12.148. [22] LiangX,ChenH,ZhangR,et al.Herbal micelles-loaded ROS-responsive hydrogel with immunomodulation and microenvironment reconstruction for diabetic wound healing[J].Biomaterials,2025,317:123076.DOI: 10.1016/j.biomaterials.2024.123076. [23] LiH,WenH,ZhangH,et al.A multifunctional dihydromyricetin-loaded hydrogel for the sequential modulation of diabetic wound healing and glycemic control[J/OL].Burns Trauma,2025,13:tkaf024[2025-08-25].https://pubmed.ncbi.nlm.nih.gov/40757164/.DOI: 10.1093/burnst/tkaf024. [24] ShuH,ZhangT,JiangY,et al.Mechanoregulative hydrogel facilitates rapid scarless healing by self-adaptive control of wound niche at different stages[J].Sci Adv,2025,11(21):eadv9895.DOI: 10.1126/sciadv.adv9895. [25] ChenM,WuY,ChenB,et al.Fast, strong, and reversible adhesives with dynamic covalent bonds for potential use in wound dressing[J].Proc Natl Acad Sci U S A,2022,119(29):e2203074119.DOI: 10.1073/pnas.2203074119. [26] ChenM,MurphyBB,WangY,et al.SMART silly putty: stretchable, malleable, adherable, reusable, and tear-resistible hydrogels[J].Small,2023,19(6):e2205854.DOI: 10.1002/smll.202205854. [27] LuCH,YuCH,YehYC.Engineering nanocomposite hydrogels using dynamic bonds[J].Acta Biomater,2021,130:66-79.DOI: 10.1016/j.actbio.2021.05.055. [28] ZhangX,GanJ,FanL,et al.Bioinspired adaptable indwelling microneedles for treatment of diabetic ulcers[J].Adv Mater,2023,35(23):e2210903.DOI: 10.1002/adma.202210903. [29] ChenY,WangX,TaoS,et al.Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties[J].Mil Med Res,2023,10(1):37.DOI: 10.1186/s40779-023-00473-9. [30] ZhouY,DaiF,ZhaoS,et al.pH and glucose dual-responsive hydrogels promoted diabetic wound healing by remodeling the wound microenvironment[J].Adv Healthc Mater,2025,14(15):e2500810.DOI: 10.1002/adhm.202500810. [31] ZanX,YangD,XiaoY,et al.Facile general injectable gelatin/metal/tea polyphenol double nanonetworks remodel wound microenvironment and accelerate healing[J].Adv Sci (Weinh),2024,11(9):e2305405.DOI: 10.1002/advs.202305405. [32] ZhangS,HuW,ZhaoY,et al.Bidirectional modulation of glycolysis using a multifunctional nanocomposite hydrogel promotes bone fracture healing in type 2 diabetes mellitus[J].Bioact Mater,2025,50:152-170.DOI: 10.1016/j.bioactmat.2025.03.020. [33] ChenX,WuY,JiaS,et al.Fibroblast: a novel target for autoimmune and inflammatory skin diseases therapeutics[J].Clin Rev Allergy Immunol,2024,66(3):274-293.DOI: 10.1007/s12016-024-08997-1. [34] ZhaoQ,ShaoT,ZhuY,et al.An MRTF-A-ZEB1-IRF9 axis contributes to fibroblast-myofibroblast transition and renal fibrosis[J].Exp Mol Med,2023,55(5):987-998.DOI: 10.1038/s12276-023-00990-6. [35] SolimanH,TungLW,RossiF.Fibroblast and myofibroblast subtypes: single cell sequencing[J].Methods Mol Biol,2021,2299:49-84.DOI: 10.1007/978-1-0716-1382-5_4. [36] YounesiFS,MillerAE,BarkerTH,et al.Fibroblast and myofibroblast activation in normal tissue repair and fibrosis[J].Nat Rev Mol Cell Biol,2024,25(8):617-638.DOI: 10.1038/s41580-024-00716-0. [37] WangZC,ZhaoWY,CaoY,et al.The roles of inflammation in keloid and hypertrophic scars[J].Front Immunol,2020,11:603187.DOI: 10.3389/fimmu.2020.603187. [38] ZhangC,SongW,GuoX,et al.Piezoelectric nanocomposite electrospun dressings: tailoring mechanics for scar-free wound recovery[J].Biomater Adv,2025,167:214119.DOI: 10.1016/j.bioadv.2024.214119. -
图 1 3种水凝胶冷冻干燥后的微观结构 扫描电子显微镜 ×500。1A、1B、1C.分别为PVA-BA水凝胶、PVA-BA-S水凝胶、PVA-BA-B水凝胶,均呈现均匀的多孔结构
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542,PVA-BA-B末尾的B指水凝胶中负载的药物BML-284
图 2 3种水凝胶的傅里叶变换红外光谱
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542,PVA-BA-B末尾的B指水凝胶中负载的药物BML-284
图 3 3种水凝胶的X射线衍射图谱
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542,PVA-BA-B末尾的B指水凝胶中负载的药物BML-284
图 4 2种水凝胶在不同pH值磷酸盐缓冲液中浸泡各时间点的药物累计释放率（样本数为3,
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542,PVA-BA-B末尾的B指水凝胶中负载的药物BML-284
图 5 4组人皮肤成纤维细胞培养24 h后Ⅰ型胶原蛋白和Ⅲ型胶原蛋白的表达情况 Alexa Fluor 488-4',6-二脒基-2苯基吲哚 ×200。5A、5B、5C、5D.分别为对照组、单纯激活组、PVA-BA组、PVA-BA-S组细胞中Ⅰ型胶原蛋白的表达情况,图5D的蛋白表达显著低于图5B、5C,高于图5A；5E、5F、5G、5H.分别为对照组、单纯激活组、PVA-BA组、PVA-BA-S组细胞中Ⅲ型胶原蛋白的表达情况,图5H的蛋白表达显著低于图5F、5G,高于图5E
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542；对照组细胞常规培养,后3组细胞均经重组人转化生长因子-β1蛋白处理24 h,之后单纯激活组细胞常规培养,PVA-BA组、PVA-BA-S组细胞分别用PVA-BA水凝胶浸提液、PVA-BA-S水凝胶浸提液培养；细胞核阳性染色为蓝色,Ⅰ型胶原蛋白和Ⅲ型胶原蛋白阳性染色均为绿色
图 6 4组人皮肤成纤维细胞培养24 h后Ⅰ型胶原蛋白和Ⅲ型胶原蛋白的蛋白表达水平（样本数为3,
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542；对照组细胞常规培养,后3组细胞均经重组人转化生长因子-β1蛋白处理24 h,之后单纯激活组细胞常规培养,PVA-BA组、PVA-BA-S组细胞分别用PVA-BA水凝胶浸提液、PVA-BA-S水凝胶浸提液培养；以平均荧光强度表示蛋白表达水平；与对照组比较,aP<0.05；与单纯激活组比较,bP<0.05；与PVA-BA组比较,cP<0.05
图 7 3组HaCaT细胞培养24 h后角蛋白5的蛋白表达情况 Alexa Fluor 488-4',6-二脒基-2苯基吲哚 ×200。7A、7B、7C.分别为对照组、PVA-BA组、PVA-BA-B组,图7C中蛋白表达显著高于图7A、7B
注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-B末尾的B指水凝胶中负载的药物BML-284；对照组细胞常规培养,PVA-BA组、PVA-BA-B组细胞分别用PVA-BA水凝胶浸提液、PVA-BA-B水凝胶浸提液培养；细胞核阳性染色为蓝色,角蛋白5阳性染色为绿色
Table 1. 用于实时荧光定量反转录PCR检测的基因引物序列和产物大小
基因名称 引物序列（5'→3'） 产物大小（bp） 上游引物 下游引物 3-磷酸甘油醛脱氢酶 CTGACTTCAACAGCGACACC GTGGTCCAGGGGTCTTACTC 107 α-平滑肌肌动蛋白 CTATGCCTCTGGACGCACAACT CAGATCCAGACGCATGATGGCA 108 转化生长因子-β TACCTGAACCCGTGTTGCTCTC GTTGCTGAGGTATCGCCAGGAA 95 Smad2 GGGTTTTGAAGCCGTCTATCAGC CCAACCACTGTAGAGGTCCATTC 108 Smad3 TGAGGCTGTCTACCAGTTGACC GTGAGGACCTTGTCAAGCCACT 102 Ⅰ型胶原蛋白 GATTCCCTGGACCTAAAGGTGC AGCCTCTCCATCTTTGCCAGCA 123 Ⅲ型胶原蛋白 TGGTCTGCAAGGAATGCCTGGA TCTTTCCCTGGGACACCATCAG 101 β-连环蛋白 CACAAGCAGAGTGCTGAAGGTG GATTCCTGAGAGTCCAAAGACAG 165 基质金属蛋白酶9 GCCACTACTGTGCCTTTGAGTC CCCTCAGAGAATCGCCAGTACT 119 E-钙黏蛋白 GCCTCCTGAAAAGAGAGTGGAAG TGGCAGTGTCTCTCCAAATCCG 121 N-钙黏蛋白 CCTCCAGAGTTTACTGCCATGAC GTAGGATCTCCGCCACTGATTC 102 
下载: 导出CSV
Table 2. 4组人皮肤成纤维细胞培养24 h后TGF-β通路相关因子的mRNA表达水平比较（
组别 样本数 TGF-β Ⅰ型胶原蛋白 Ⅲ型胶原蛋白 α-平滑肌肌动蛋白 Smad2 Smad3 对照组 3 1.00±0.05 1.00±0.07 1.00±0.12 1.00±0.07 1.00±0.07 1.00±0.03 单纯激活组 3 2.03±0.22a 2.63±0.10a 2.36±0.28a 3.08±0.45a 1.57±0.10a 2.44±0.35a PVA-BA组 3 2.05±0.08a 2.53±0.14a 2.33±0.08a 2.98±0.22a 1.58±0.05a 2.34±0.06a PVA-BA-S组 3 1.40±0.03abc 1.30±0.04abc 1.47±0.08abc 1.47±0.06bc 0.87±0.05bc 1.49±0.11abc F值 52.84 239.36 48.88 52.02 83.61 41.69 P值 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-S中S指水凝胶中负载的药物SB431542；对照组细胞常规培养,后3组细胞均经重组人转化生长因子-β1（TGF-β1）蛋白处理24 h,之后单纯激活组细胞常规培养,PVA-BA组、PVA-BA-S组细胞分别用PVA-BA水凝胶浸提液、PVA-BA-S水凝胶浸提液培养；F值、P值为4组间各指标总体比较所得；与对照组比较,aP<0.05；与单纯激活组比较,bP<0.05；与PVA-BA组比较,cP<0.05
下载: 导出CSV
Table 3. 3组HaCaT细胞培养24 h后Wnt通路相关因子的mRNA表达水平比较（
组别 样本数 β-连环蛋白 基质金属蛋白酶9 E-钙黏蛋白 N-钙黏蛋白 对照组 3 1.001±0.059 1.01±0.17 1.00±0.07 1.00±0.04 PVA-BA组 3 1.107±0.022 1.03±0.26 1.04±0.10 1.03±0.06 PVA-BA-B组 3 2.342±0.091 1.83±0.38 0.68±0.10 1.99±0.12 F值 407.49 8.21 15.19 150.86 P值 <0.001 0.019 0.004 <0.001 P1值 0.186 0.995 0.881 0.922 P2值 <0.001 0.028 0.010 <0.001 P3值 <0.001 0.031 0.006 <0.001 注：PVA-BA为聚乙烯醇-硼酸,PVA-BA-B末尾的B指水凝胶中负载的药物BML-284；对照组细胞常规培养,PVA-BA组、PVA-BA-B组细胞分别用PVA-BA水凝胶浸提液、PVA-BA-B水凝胶浸提液培养；F值、P值为3组间各指标总体比较所得；P1值、P2值分别为PVA-BA组、PVA-BA-B组与对照组各指标比较所得；P3值为PVA-BA组与PVA-BA-B组各指标比较所得
下载: 导出CSV
-
下载:
图(8) / 表(3)
计量
- 文章访问数: 168
- HTML全文浏览量: 110
- PDF下载量: 9
- 被引次数: 0
