正极性驻极体5-氟尿嘧啶贴剂对瘢痕组织中胶原合成的影响
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摘要
为了研究5-氟尿嘧啶(5-FU)贴剂和正极性驻极体5-FU贴剂抑制增生性瘢痕(HS)生长的机制,将常温电晕充电制备的正极性聚丙烯(PP)驻极体的充电面与制备的5-FU贴剂的背衬层相结合,制成了不同等效表面电位(分别为1 000 V和2 000 V)的正极性驻极体5-FU贴剂,然后将5-FU贴剂和正极性驻极体5-FU贴剂分别作用于创伤SD大鼠创面,通过苏木精-伊红(HE)染色、Masson染色和免疫组织化学方法进行了对比。研究结果表明:(1)SD大鼠创面自然愈合4周时间后形成增生性瘢痕组织;(2)5-FU贴剂和正极性驻极体5-FU贴剂通过减少瘢痕组织内Ⅰ型胶原和Ⅲ型胶原的表达量来抑制增生性瘢痕的生长;(3)正极性驻极体5-FU贴剂抑制增生性瘢痕生长的疗效优于5-FU贴剂,正极性驻极体5-FU贴剂抑制增生性瘢痕生长的疗效与驻极体的等效表面电位大小成正比。因此可得结论:正极性驻极体5-FU贴剂可有效增加模型药物在皮肤内的储存量,抑制增生性瘢痕的生长。
To study the effects of 5-fluorouracil(5-FU) patch and positive electret 5-FU patch on inhibition of hypertrophic scar(HS) growth and its mechanism, we prepared positive electret 5-FU patches with different surface potential by covering the charged side of the corona charged positive polypropylene(PP) electret on the back layer of the 5-FU patch. The 5-FU patch and positive electret 5-FU patches were applied to the surface of the wound in SD rats. The HE staining, Masson staining and immunohistochemical methods were used. The research results indicate that(1) The hypertrophic scar is formed after natural healing for 4 weeks.(2) Both the 5-FU patch and positive electret 5-FU patch can reduce the expression of type Ⅰ collagen and type Ⅲ collagen in scar tissue to inhibit the growth of HS.(3) The positive electret 5-FU patch has better inhibition effect in HS growth than the 5-FU patch. And the inhibition effect is proportional to the effective surface potential of the electret. The conclusion can be drawn that the positive electret 5-FU patch can effectively increase the model drug stores in the skin,and restrain the growth of the hypertrophic scar.
To study the effects of 5-fluorouracil(5-FU) patch and positive electret 5-FU patch on inhibition of hypertrophic scar(HS) growth and its mechanism, we prepared positive electret 5-FU patches with different surface potential by covering the charged side of the corona charged positive polypropylene(PP) electret on the back layer of the 5-FU patch. The 5-FU patch and positive electret 5-FU patches were applied to the surface of the wound in SD rats. The HE staining, Masson staining and immunohistochemical methods were used. The research results indicate that(1) The hypertrophic scar is formed after natural healing for 4 weeks.(2) Both the 5-FU patch and positive electret 5-FU patch can reduce the expression of type Ⅰ collagen and type Ⅲ collagen in scar tissue to inhibit the growth of HS.(3) The positive electret 5-FU patch has better inhibition effect in HS growth than the 5-FU patch. And the inhibition effect is proportional to the effective surface potential of the electret. The conclusion can be drawn that the positive electret 5-FU patch can effectively increase the model drug stores in the skin,and restrain the growth of the hypertrophic scar.
引文
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[17]孔德平,陈凯.5-氟尿嘧啶对增生性瘢痕的作用研究[J].重庆医学,2015,44(8):1029-1031.KONG Deping,CHEN Kai.The effects of 5-fluorouracil on hypertrophic scar of rabbit ears[J].Chongqing Medical Journal,2015,44(8):1029-1031.
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[19]JIANG J,LIANG Y Y,DONG F J,et al.Study of electret effect of rat skin by thermally stimulated discharge analysis[J].Journal of Electrostatics,2012,70(3):258-263.
[20]梁媛媛,江键,程亮,等.负极性聚丙烯驻极体美洛昔康贴剂对大鼠皮肤结构的影响[J].解剖学杂志,2009,32(4):502-505.LIANG Yuanyuan,JIANG Jian,CHENG Liang,et al.Influences of negative polypropylene electret meloxicam patch on percutaneous absorption of drug in rat[J].Chinese Journal of Anatomy,2009,32(4):502-505.
[21]苑旺,梁媛媛,崔黎丽,等.正极性聚丙烯驻极体对糖尿病大鼠皮肤结构的影响[J].中国医学物理学杂志,2015,32(6):835-840.YUAN Wang,LIANG Yuanyuan,CUI Lili,et al.Effects of positive electrets on skin structure of diabetic rats[J].Chinese Journal of Medical Physics,2015,32(6):835-840.
[22]TU Y,WANG X X,LU Y,et al.Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret[J].International Journal of Nanomedicine,2016,11:5549-5561.
[23]黄平,徐立丽,梁媛媛,等.负极性驻极体与5-氟尿嘧啶对大鼠创面愈合的影响[J].解剖学杂志,2017,40(2):176-180.HUANG Ping,XU Lili,LIANG Yuanyuan,et al.Effect of negative polypropylene electret and 5-fluorouracil on skin wound healing of rats[J].Chinese Journal of Anatomy,2017,40(2):176-180.
[2]ZHANG K,GARNER W,COHEN L,et al.Increased typesⅠandⅢcollagen and transforming growth factor-beta 1 m RNA and protein in hypertrophic burn scar[J].Journal of Investigative Dermatology,1995,104(5):750-754.
[3]周游,王婷,于尔特.增生性瘢痕形成的病理机制和当代治疗现状[J].解剖科学进展,2016(4):432-435.ZHOU You,WANG Ting,YU Erte.Progress of pathogenesis and therapy of hypertrophic scar[J].Progress of Anatomical Sciences,2016(4):432-435.
[4]CALISKAN E,GAMSIZKAN M,ACIKGOZ G,et al.Intralesional treatments for hypertrophic scars:comparison among corticosteroid,5-fluorouracil and botulinum toxin in rabbit ear hypertrophic scar model[J].European Review for Medical and Pharmacological Sciences,2016,20(8):1603-1608.
[5]HUSSAIN A,HAQUE M W,SINGH S K,et al.Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using design expert:partⅡ[J].Drug Delivery,2016,23(4):1242-1253.
[6]WANG X C,CAO P,LIU J,et al.5-aminolaevulinic acid-based photodynamic therapy restrains pathological hyperplasia of fibroblasts[J].Medical Science Monitor,2017,23:46-56.
[7]陈钢进,肖慧明,夏钟福.电晕充电多孔PTFE/PP复合驻极体过滤材料的电荷存储特性[J].物理学报,2006,55(5):2464-2469.CHEN Gangjin,XIAO Huiming,XIA Zhongfu.Charge storage characteristics in hybrid electret film consisting of porous PTFE and PP with negative corona charging[J].Acta Physica Sinica,2006,55(5):2464-2469.
[8]李鹏程,周蓉,陈莹,等.聚丙烯驻极体过滤材料的充电工艺研究[J].青岛大学学报,2015,30(2):52-56.LI Pengcheng,ZHOU Rong,CHEN Ying,et al.Research on process and charge properties of polypropylene electret filter[J].Journal of Qingdao University,2015,30(2):52-56.
[9]包家立,胡亚楠.射频电磁场的健康效应[J].高电压技术,2016,42(8):2353-2366.BAO Jiali,HU Yanan.Health effects of radio-frequency electromagnetic fields[J].High Voltage Engineering,2016,42(8):2353-2366.
[10]曲敏,毕卓悦,唐雨萌,等.生物电磁技术应用及其相关健康风险评估对策[J].高电压技术,2015,41(8):2625-2634.QU Min,BI Zhuoyue,TANG Yumeng,et al.Application of bio-electromagnetic technique and its related health risk assessment strategy[J].High Voltage Engineering,2015,41(8):2625-2634.
[11]王春晓,郭鑫,徐立丽,等.驻极体促进5-氟尿嘧啶体外经皮渗透[J].高电压技术,2016,42(5):1463-1469.WANG Chunxiao,GUO Xin,XU Lili,et al.In vitro enhancement of transdermal delivery of 5-fluorouracil by electret application[J].High Voltage Engineering,2016,42(5):1463-1469.
[12]黄平,石岩,郭鑫,等.正极性驻极体环孢菌素A贴剂的开路热刺激放电[J].高电压技术,2015,41(4):1390-1394.HUANG Ping,SHI Yan,GUO Xin,et al.Open thermally stimulated discharge of positive electret cyclosporine A patch[J].High Voltage Engineering,2015,41(4):1390-1394.
[13]CUI L L,LIANG Y Y,MA L,et al.The combinational effect of PP electret and monlein on transdermal delivery of cyclosporin A in vitro[J].Journal of Electrostatics,2013,71(3):224-227.
[14]CUI L L,LIU H,MA L,et al.Enhanced reansdermal delivery of cyclosporin A by elecyret and ethyloleate[J].IEEE Transactions on Dielectrics and Electrical Insulation,2012,19(4):1191-1194.
[15]MOUNIR J H,KENNETH F,JAMES J Y,et al.5-fluorouracil treatment of problematic scars[J].Heridasy Cicatrizacion,2009,123(1):139-148.
[16]ZHANG Z,WO Y,ZHANG Y X,et al.In vitro study of ethosome penetration in human skin and hypertophic scar tissus[J].Nanomedicine,2012,8(6):1026-1033.
[17]孔德平,陈凯.5-氟尿嘧啶对增生性瘢痕的作用研究[J].重庆医学,2015,44(8):1029-1031.KONG Deping,CHEN Kai.The effects of 5-fluorouracil on hypertrophic scar of rabbit ears[J].Chongqing Medical Journal,2015,44(8):1029-1031.
[18]徐立丽,黄平,苑旺,等.正极性驻极体外静电场对5-氟尿嘧啶贴剂中药物释放的影响[J].高电压技术,2017,43(6):1925-1929.XU Lili,HUANG Ping,YUAN Wang,et al.Effect of external elecrrostatics field of postive polypropylene electret on release of5-fluoroyracil from adhesive patch[J].High Voltage Engineering,2017,43(6):1925-1929.
[19]JIANG J,LIANG Y Y,DONG F J,et al.Study of electret effect of rat skin by thermally stimulated discharge analysis[J].Journal of Electrostatics,2012,70(3):258-263.
[20]梁媛媛,江键,程亮,等.负极性聚丙烯驻极体美洛昔康贴剂对大鼠皮肤结构的影响[J].解剖学杂志,2009,32(4):502-505.LIANG Yuanyuan,JIANG Jian,CHENG Liang,et al.Influences of negative polypropylene electret meloxicam patch on percutaneous absorption of drug in rat[J].Chinese Journal of Anatomy,2009,32(4):502-505.
[21]苑旺,梁媛媛,崔黎丽,等.正极性聚丙烯驻极体对糖尿病大鼠皮肤结构的影响[J].中国医学物理学杂志,2015,32(6):835-840.YUAN Wang,LIANG Yuanyuan,CUI Lili,et al.Effects of positive electrets on skin structure of diabetic rats[J].Chinese Journal of Medical Physics,2015,32(6):835-840.
[22]TU Y,WANG X X,LU Y,et al.Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret[J].International Journal of Nanomedicine,2016,11:5549-5561.
[23]黄平,徐立丽,梁媛媛,等.负极性驻极体与5-氟尿嘧啶对大鼠创面愈合的影响[J].解剖学杂志,2017,40(2):176-180.HUANG Ping,XU Lili,LIANG Yuanyuan,et al.Effect of negative polypropylene electret and 5-fluorouracil on skin wound healing of rats[J].Chinese Journal of Anatomy,2017,40(2):176-180.