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复方地塞米松-氨氯地平凝胶经皮渗透能力及其对缺血随意皮瓣成活的影响 被引量:2

PERCUTANEOUS PENETRATION ABILITY OF DEXAMETHASONE-AMLODIPINE BESYLATE COMPOUND GEL AND ITS EFFECT ON SURVIVAL OF ISCHEMIC RANDOM SKIN FLAP
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摘要 目的地塞米松(dexamethasone,DXM)可通过调节中性粒细胞及细胞因子平衡,提高皮瓣缺血再灌注的耐受力;氨氯地平(amlodipine besylate,AB)具有选择性扩张周围血管、解除血管平滑肌痉挛等作用。探讨0.3%DXM-0.5%AB复方凝胶经皮渗透能力及其对大鼠缺血随意皮瓣成活的影响。方法取羧甲基纤维素钠制备凝胶基质,分别制备含0.3%DXM及0.5%AB的复方凝胶(D组);取复方凝胶再制备含3%氮酮(azone,AZ)/2%丙二醇(progylene glycol,PG)、3%AZ、2%PG的复方凝胶(A、B、C组);另外制备含3%AZ及2%PG的0.3%DXM凝胶(E组)以及含3%AZ及2%PG的0.5%AB凝胶(F组)。采用Franz扩散池紫外分光光度法检测上述凝胶中DXM和AB经大鼠离体腹部皮肤的累积渗透量。取50只SD大鼠随机分为5组(n=10),于背部制备100mm×10mm随意皮瓣后分别每日将2g含3%AZ及2%PG的复方凝胶(A1组)、0.3%DXM凝胶(B1组)、0.5%AB凝胶(C1组)和凝胶基质(D1组)涂抹至皮瓣表面,以及腹腔注射DXM(5mg/kg)及AB(2mg/kg)为E1组,术后7d采用面积测定法检测皮瓣的成活面积。取24只大鼠随机分为2组(n=12),同上法制备随意皮瓣后,A2组术后即刻于皮瓣表面涂抹含3%AZ及2%PG的复方凝胶2g,B2组腹腔注射DXM(5mg/kg)和AB(2mg/kg),2、6h后检测皮瓣组织中DXM及AB累积量。结果各组DXM、AB的累积渗透量随用药时间延长而增加,差异均有统计学意义(P<0.05)。A组中DXM、AB的累积渗透量与E、F组比较,差异无统计学意义(P>0.05),但高于B、C组(P<0.01);与D组比较,A、B、C组DXM及AB累积渗透量均增高,差异有统计学意义(P<0.05)。术后7d A1~E1组皮瓣成活面积分别为(695.0±4.6)、(439.3±7.1)、(477.5±14.5)、(215.2±3.8)、(569.4±9.7)mm2,A1组成活面积大于其他组(P<0.05)。术后2、6h,A2组皮瓣中DXM、AB累积量均高于B2组,差异有统计学意义(P<0.05)。结论0.3%DXM/0.5%AB复方凝胶中的DXM和AB可渗透进入大鼠皮肤组织,并能提高缺血随意皮瓣的成活面积。 Objective Dexamethasone (DXM) can regulate the balance of neutrophil and cytokine and enhance the ischemia-reperfusion tolerance of the skin flap; amlodipine besylate (AB) can selectively expand the peripheral blood vessels and relieve the vascular smooth muscle spasm. To investigate the percutaneous penetration ability of DXM/AB compound gel and evaluate its effect on survival of ischemic skin flap. Methods Sodium carboxymethylcellulose was used to make blank gel,which was mixed in DXM,AB,azone (AZ),and progylene glycol (PG) respectively to make the compound gel containing 0.3%DXM/0.5%AB only (group D),the compound gel containing 3%AZ/2%PG,3%AZ,and 2%PG (groups A,B,and C),the 0.3%DXM gel containing 3%AZ/2%PG (group E),the 0.5%AB gel containing 3%AZ/2%PG (group F). The accumulative penetration of DXM and AB in compound gel,0.3%DXM gel,0.5%AB gel through excised rat skin and its penetration within flap tissue were investigated by ultraviolet spectrophotometry. Fifty SD rats were selected to make 100 mm × 10 mm random flap at the back,and were randomly divided into 5 groups according to different gels which were used to treat flaps (n=10):compound gel group (group A1),0.3%DXM gel group (group B1),0.5%AB gel group (group C1),blank gel group (group D1),and peritoneal injection of DXM (5 mg/kg) and AB (2 mg/kg) (group E1). The survival area of ischemic random skin flap was measured on the 7th day by planimetry. Twenty-four SD rats were selected to make 100 mm × 10 mm random flap at the back,and were randomly divided into 2 groups (n=12). The accumulative penetration of DXM and AB within skin flap were alsodetected at 2 and 6 hours after application of 2 g of compound gel containing 3%AZ/2%PG (group A2) and peritoneal injection AB (2 mg/kg) / DXM (5 mg/kg) (group B2). Results The accumulative penetration of DXM and AB in compound gel were increased in time-dependent manner (P 〈0.05),and it was the highest in group A,and was signifi cantly higher than that in group B and group C (P〈 0.01),but there was no signifi cant difference when compared with group E or group F (P 〉0.05). The accumulative penetration of DXM and AB in groups A,B,and C were signifi cant higher than that in group D (P 〈0.05). After 7 days,the survival area of flaps in groups A1,B1,C1,D1,and E1 were (695.0 ± 4.6),(439.3 ± 7.1),(477.5 ± 14.5),(215.2 ± 3.8),and (569.4 ± 9.7) mm^2,respectively; group A1 was significantly higher than other groups (P 〈0.05). After 2 and 6 hours,the quantities of DXM and AB in skin flap of group A2 were signifi cantly higher than that of group B2 (P〈 0.05). Conclusion In 0.3%DXM/0.5%AB compound gel,DXM and AB might penetrate into skin tissue,which could significantly increase the survival area of ischemic skin flap.
出处 《中国修复重建外科杂志》 CAS CSCD 北大核心 2010年第5期566-570,共5页 Chinese Journal of Reparative and Reconstructive Surgery
基金 兰州大学医学科研基金资助项目(LZUYX200822)~~
关键词 地塞米松 氨氯地平 复方凝胶 透皮给药 随意皮瓣 缺血坏死 大鼠 Dexamethasone Amlodipine besylate Compound gel Percutaneous penetrationRandom skin flap Isohemic necrosis Rats
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