前列地尔对烫伤大鼠创面愈合的影响及其机制

Effect of alprostadil on wound healing of scalded rats and the mechanism

目的探讨前列地尔对烫伤大鼠创面愈合的影响及其机制。方法取48只SD大鼠，按随机数字表法分为假伤组、单纯烫伤组、氯化锂组、前列地尔组，每组12只。假伤组大鼠背部模拟致假伤，余3组大鼠背部致30%体表总面积（TBSA）深Ⅱ度烫伤。假伤组和单纯烫伤组大鼠伤后即刻尾静脉推注1 mL生理盐水，氯化锂组、前列地尔组大鼠分别尾静脉推注1 mL氯化锂、前列地尔注射液，均为1次/d，持续14 d。观察各组大鼠伤后7、10、14 d创面大体情况、创面愈合率及伤后14 d创面Wnt1、β连环蛋白mRNA及蛋白表达水平。对数据行析因设计方差分析、单因素方差分析、SNK－q检验、t检验及Bonferroni校正。结果（1）伤后7 d，各组烫伤大鼠创面形成干痂，渗出不多。伤后10 d，单纯烫伤组大鼠创面焦痂覆盖，渗出少许；氯化锂大鼠组创面焦痂覆盖，部分有痂下愈合；前列地尔组大鼠创面部分焦痂剥脱，部分愈合，新愈合皮肤红润。伤后14 d，单纯烫伤组创面部分痂下愈合，有渗出；氯化锂组大鼠创面大部痂皮剥脱，部分创面愈合，有渗出；前列地尔组大鼠创面基本愈合，毛发生长旺盛。（2）伤后7 d，单纯烫伤组、氯化锂组、前列地尔组大鼠创面愈合率相近（F＝0.41，P〉0.05）。伤后10、14 d，前列地尔组、氯化锂组大鼠创面愈合率明显高于单纯烫伤组（q＝5.73、17.45、26.30、11.28，P〈0.05），前列地尔组大鼠创面愈合率明显高于氯化锂组（q＝32.03、28.73，P〈0.05）。（3）伤后14 d，前列地尔组、氯化锂组大鼠创面Wnt1、β连环蛋白mRNA表达量明显高于单纯烫伤组（q＝65.40、19.16、66.79、18.41，P〈0.05），单纯烫伤组大鼠创面Wnt1、β连环蛋白mRNA表达量明显高于假伤组（t＝14.86、4.46，P〈0.05）。（4）伤后14 d，氯化锂组、前列地尔组大鼠创面Wnt1、β连环蛋白表达量分别为0.98±0.05、0.98±0.06，0.97±0.06、1.00±0.06，明显高于单纯烫伤组的0.49±0.04、0.66±0.04（q＝34.62、22.38、33.61、23.47，P〈0.05），单纯烫伤组大鼠创面Wnt1、β连环蛋白表达量明显高于假伤组的0.29±0.03、0.31±0.03（q＝14.73、23.88，P〈0.05）。结论前列地尔可通过提高大鼠创面Wnt1、β连环蛋白的表达，激活Wnt/β连环蛋白信号通路，从而促进创面愈合。

ObjectiveTo explore effect of alprostadil on wound healing of scalded rats and the mechanism.MethodsAccording to random number table method, forty-eight Sprague Dawley rats were divided into sham scald group, simple scald group, lithium chloride group, and alprostadil group, with 12 rats in each group. Rats in sham injury group were sham injured on the back, and rats in the other three groups were inflicted with 30% total body surface area deep partial thickness scald on the back.Immediately after scald, rats in sham scald group and simple scald group were injected with 1 mL saline through caudal vein, and rats in lithium chloride group and alprostadil group were injected respectively with 1 mL lithium chloride and alprostadil through caudal vein. Saline, lithium chloride, and alprostadil were injected once in a day and lasted for 14 days. General wound appearance and wound healing rate on post scald day （PSD） 7, 10, 14 were observed and calculated. Expressions of protein and mRNA of Wnt1 and β-catenin on PSD 14 were detected. Data were processed with analysis of variance of factorial design, one-way analysis of variance, Student Newman Keuls q test, t test, and Bonferroni correction.Results（1） On PSD 7, wounds of scalded rats in each group formed dry eschar and had little exudation. On PSD 10, wounds of rats in simple scald group were covered with eschar, with little exudation, and wounds of rats in lithium chloride group were covered with eschar, and partial wounds healed under the eschar. On PSD 10, partial eschar of rats in alprostadil group desquamated; partial wounds healed; newly burned skin was ruddy. On PSD 14, partial wounds of rats in simple scald group were healed under eschar with little exudation. On PSD 14, most of the eschar of rats in lithium chloride group were desquamated with patial wounds healed and little exudation. On PSD 14, wounds of rats in alprostadil group were basically healed with vigorously growing hair on the back. （2） On PSD 7, the wound healing rates of rats in simple scald group, lithium chloride group, and alprostadil group were close （F=0.41, P〉0.05）. On PSD 10 and 14, wound healing rate of rats in lithium chloride group and alprostadil group were significantly higher than that in simple scald group （q=5.73, 17.45, 26.30, 11.28, P〈0.05）, and wound healing rate of rats in alprostadil group was significantly higher than that in lithium chloride group （q=32.03, 28.73, P〈0.05）. （3） On PSD 14, the mRNA expressions of Wnt1 and β-catenin of rats in lithium chloride group and alprostadil group were significantly higher than those in simple scald group （q=65.40, 19.16, 66.79, 18.41, P〈0.05）, and the mRNA expressions of Wnt1 and β-catenin of rats in simple scald group was significantly higher than those in sham scald group （t=14.86, 4.46, P〈0.05）. （4） On PSD 14, the protein expressions of Wnt1 and β-catenin of rats in lithium chloride group and alprostadil group were 0.98±0.05, 0.98±0.06, 0.97±0.06, and 1.00±0.06, which were significantly higher than 0.49±0.04 and 0.66±0.04 of rats in simple scald group （q=34.62, 22.38, 33.61, 23.47, P〈0.05）. On PSD 14, the protein expressions of Wnt1 and β-catenin of rats in simple scald group was significantly higher than 0.29±0.03 and 0.31±0.03 of rats in sham scald group （q=14.73, 23.88, P〈0.05）.ConclusionsAlprostadil can accelerate wound healing through activating Wnt/β-catenin signal pathway and upregulating the expressions of Wnt1 and β-catenin.