抗菌肽LL-37对大鼠背部皮瓣存活的影响  

Effect of cathelicidin LL-37 on survival of random skin flap on the back in rats

作　　者：何志湘[1] 王九松 许云华[1] 宋剑刚[1] 贺强[1] HE Zhi-xiang;WANG Jiu-song;XU Yun-hua;SONG Jian-gang;HE Qiang(Department of Hand and Foot Surgeryt Nanhua Hospital,Nanhua University,Hengyang 421002,China)

机构地区：[1]南华大学附属南华医院手足外科,湖南衡阳421002

出　　处：《中国矫形外科杂志》2021年第20期1868-1872,共5页Orthopedic Journal of China

基　　金：湖南省卫计委科研计划重点项目(编号:A2017018)。

摘　　要：[目的]比较不同剂量抗菌肽LL-37干预对大鼠背部随意皮瓣存活的影响。[方法]75只SD大鼠随机分为五组,每组15只。假手术组仅切开皮瓣,其余4组采用改良“McFarlane flap”法制作大鼠随意皮瓣模型。LL-37低、中、高剂量组大鼠分别给予0.25mg/kg、0.5mg/kg和1.0mg/kgLL-37腹腔注射,假手术组和模型组等量生理盐水腹腔注射,1次/d,连续7d。观察皮瓣大体情况并测定各组大鼠皮瓣成活率;观察皮瓣组织病理学变化,检测血液或组织匀浆应激与炎性产物,以及VEGF-A和HIF-1a的mRNA和蛋白表达水平。[结果]与假手术组比较,模型组大鼠皮瓣组织结构破坏严重,伴有大量炎性细胞浸润;皮瓣成活率、平均血管密度(mean vascular density,MVD)、SOD活性及VEGF-A、HIF-1a的mRNA和蛋白表达水平均显著下调(P<0.05),而MDA、TNF-ot和IL-6含量显著上调(P<0.05)。与模型组比较,LL-37的作用呈剂量依赖性,中、高剂量组大鼠皮瓣组织结构基本恢复,少量炎性细胞浸润,皮瓣成活率、MVD、SOD活性及VEGF-A、HIF-1a的mRNA和蛋白表达水平均显著上调(P<0.05),MDA、TNF-a和IL-6含量显著下调(P<0.05),而LL-37低剂量组相关指标变化差异无统计学意义(P>0.05)。[结论]LL-37可促进大鼠随意型皮瓣成活,其机制可能与减轻炎症反应,降低氧化应激水平,促进皮瓣微血管形成有关。[Objective]To compare the effects of cathelicidin LL-37,an antimicrobial peptide,in different doses on the survival of random skin flap on the back in rats.[Methods]A total of 75 Sprague-Dawley male rats were randomly divided into five groups with 15 animals in each group.Only the skin of flap was cut and sutured in the sham operation group,whereas random skin flap model was created by using the modified"McFarlane flap"method in the remaining four groups.The rats in low,medium and high-dose groups had cathelicidin LL-37 given intraperitoneally in dosage of 0.25 mg/kg,0.5 mg/kg and 1.0 mg/kg respectively,whereas those in the sham group and the model group received equal volume of normal saline intraperitoneally,once per day for 7 days consecutively.The survival rate of flaps,histo-pathological changes,stress and inflammatory products,as well as the mRNA and protein expression of VEGF-A and HIF-la of the blood sample or tissue homogenate were compared among the groups.[Results]Compared with the sham group,the model groups presented severely damaged tissue structure of skin flap,accompanied with a large number of inflammatory cell infiltration;had significant down-regulation of flap survival rate,microvascular density(MVD)and superoxide dismutase(SOD),as well as mRNA and protein expression levels of VEGF-A and HIF-la(P<0.05),while significant up-regulation of malondialdehyde(MDA),TNF-a and IL-6(P<0.05).However,cathelicidin LL-37 reversed the flap effect in dose-dependent manner,the middle and high-dose groups revealed nearly normal tissue structure of skin flaps with a small amount of inflammatory cell infiltration,had significantly higher flap survival rate,significantly higher MVD and SOD levels,as well as significantly higher mRNA and protein expression levels of VEGF-A and HIF-la(P<0.05),whereas significantly lower MDA,TNF-a,and IL-6 levels(P<0.05);in contrast,the low-dose group remained unchanged in abovesaid items compared with those in the model group(P>0.05).[Conclusion]The cathelicidin LL-37 does promote th

关 键 词：随意皮瓣 抗菌肽 氧化应激 血管新生 

分 类 号：R318[医药卫生—生物医学工程]