靶向间皮角质细胞生长因子对术后腹膜粘连的预防作用

The protective effects of keratinocyte growth factor targeted mesothelium on the postoperative peritoneal adhesions

目的研究角质细胞生长因子(KGF)对大鼠腹膜粘连形成的预防作用及对腹膜粘连组织中组织纤溶酶原激活物(tPA)和纤溶酶原激活物抑制剂(PAI-1)表达的影响。方法 SD大鼠30只,随机分为3组(n=10),分别为KGF组、模型组和假手术组。7 d后处死大鼠,并参照修改后的Leach等评分系统评价粘连程度。光镜观察组织形态学变化,并用免疫组化SP法测定腹膜粘连组织中tPA和PAI-1表达情况。结果 KGF组粘连总评分结果(4.8±0.92)明显低于模型组(7.6±1.35)(P<0.01),免疫组化染色示KGF组tPA表达水平(88.41±3.92)明显高于模型组(111.63±4.04)和假手术组(100.91±1.57)(P<0.01),而PAI-1表达水平在3组之间无差异(P>0.05)。结论 KGF通过促使损伤处腹膜再生及纤溶能力恢复达到预防腹膜粘连形成,提示间皮再生可能是预防粘连形成的有效途径。

Objective To investigate the effects of keratinocyte growth factor（KGF） by promoting mesothelial regeneration on the prevention of peritonea1 adhesion formation in rats and expressions of tissue plasminogen activator（tPA） and plasminogen activator inhibitor type 1（PAI-1） in peritonea1 adhesion tissues.Methods Thirty SD rats were randomly assigned to KGF group,model group and sham-operation group,each consisting of 10 rats.All rats were killed 7 days later and the adhesion degree was evaluated by modified Leach scale.The histomorphologic changes of the adhesion tissues were observed with light microscope.The immunohistochemical technique was used to identify the expressions of tPA and PAI-1 in peritonea1 adhesion tissues.Results The gross adhesion scores were significantly lower in KGF group than in model control group（4.8±0.92 vs.7.6±1.35,P〈0.01）.The expression level of tPA was obviously higher in KGF group than in the other groups（88.41±3.92 vs.111.63±4.04,100.91±1.57;P〈0.01）.However,no significant difference was noted in PAI-1 expression among the three groups（P〉0.05）.Conclusion KGF prevents peritonea1 adhesion formation by promoting the reperitonealization of injured wound surface and the resumption of the peritonea1 fibrinolytic activity of mesothelial cells.Our observations suggest that mesothelial regeneration is an intriguing avenue for research and development of anti-adhesion strategy.