大黄素调控TLR4/NF-κB信号通路对大鼠感染性创面愈合的研究  

Research of emodin regulating TLR4/NF-κB signaling pathway on heal infected wound in rats

作　　者：张春[1] 王锦姝 王寿宇[2] 刘兵 王思懿 ZHANG Chun;WANG Jin-shu;WANG Shou-yu;LIU Bing;WANG Si-yi(Department of Trauma Surgery,TheFirst Afiliated Hospital of Dalian Medical University,Dalian 116011,Liaoning Province,China;Orthopedics Department,TheFirst Afiliated Hospital of Dalian Medical University,Dalian 116011,Liaoning Province,China)

机构地区：[1]大连医科大学附属第一医院创伤外科,辽宁大连116011 [2]大连医科大学附属第一医院骨科,辽宁大连116011

出　　处：《中国临床药理学杂志》2024年第10期1483-1487,共5页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁省“兴辽英才计划”基金资助项目(XLYC1802014)。

摘　　要：目的研究大黄素对大鼠感染性创面愈合的作用,及其对Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路的调节作用。方法用全层皮肤缺损法构建感染性创面大鼠模型,将造模成功的大鼠随机分为模型组、对照组和低、中、高剂量实验组,每组12只;另取12只正常大鼠作为正常组。低、中、高剂量实验组分别外敷大黄素150、300、600μg·d^(-1),每次1次,同时均灌胃给予200 mg·kg^(-1)大黄素,每天1次;对照组外敷莫匹罗星软膏0.1 g·d^(-1),每天1次;正常组和模型组均灌胃给予等体积0.9%NaCl,每天1次。6组大鼠均连续给药21 d。比较各组大鼠的创面愈合率及动态血流值,用酶联免疫吸附试验法分别测定血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β水平及创面组织中羟脯氨酸(HYP)、过氧化氢酶(CAT)水平,用蛋白质印迹法测定创面组织中TLR4和NF-κB蛋白的表达水平。结果中、高剂量实验组和对照组、模型组的创面愈合率分别为(50.70±1.26)%、(75.51±0.50)%、(69.44±1.65)%和(28.58±5.09)%;中、高剂量实验组和对照组、模型组、正常组的动态血流值分别为(123.71±3.71)、(155.61±2.47)、(146.29±2.04)、(79.47±4.76)和(158.00±1.93)mL·min^(-1),TNF-α分别为(81.05±2.32)、(56.69±1.59)、(69.53±2.39)、(139.46±2.46)和(46.49±5.71)ng·L^(-1),IL-1β分别为(59.87±0.83)、(42.66±1.30)、(48.37±3.34)、(88.79±1.84)和(33.93±2.19)ng·L^(-1),HYP分别为(24.79±0.82)、(31.12±1.16)、(25.83±1.12)、(16.88±2.20)和(32.95±1.18)μg·mg^(-1),CAT分别为(24.99±1.47)、(34.52±1.26)、(31.00±1.15)、(13.70±2.09)和(34.23±0.70)U·mg^(-1),TLR4蛋白相对水平分别为0.74±0.05、0.53±0.05、0.55±0.04、1.09±0.07和0.23±0.05,NF-κB蛋白相对水平分别为0.69±0.06、0.44±0.04、0.52±0.03、1.10±0.04和0.22±0.10。中、高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论大黄素能够改善大鼠感染性创Objective To investigate the effects of emodin on the healing of infected wound and the regulation of Toll-likereceptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway in rats.Methods The model of infectious wounds rats were constructed by the full-thickness skin defect method.The successful model rats were randomly divided into model group,control group and experimental-L,-M,-H groups with 12 rats per group;another 12 normal rats were taken as the normal group.Experimental-L,-M,-H groups was applied with emodin 150,300 and 600μg·d^(-1)and 200 mg·kg^(-1)emodin by gavage,respectively.Control group was applied with mopirolacin cream 0.1 g·d^(-1)on rat wounds,once a day.Normal and model groups were treated with 0.9%NaCl.Six groups were treated for 21 days.The wound healing rates and dynamic blood flow were measured.The levels of tumor necrosis factor(TNF)-αand interleukin(IL)-1βin serum and the hydroxyproline(HYP)and catalase(CAT)in wound tssue were measured by enzyme linked immunosorbent assay.The protein levels of TLR4 and NF-κB in wound were determined by Western blot.Results The wound healing rates of experimental-M,-H groups,control group and model group were(50.70±1.26)%,(75.51±0.50)%,(69.44±1.65)%and(28.58±5.09)%,respectively.The dynamic blood flow values of experimental-M,-H groups,control group,model group and blank group were(123.71±3.71),(155.61±2.47),(146.29±2.04),(79.47±4.76)and(158.00±1.93)mL·min^(-1);the levels of TNF-αwere(81.05±2.32),(56.69±1.59),(69.53±2.39),(139.46±2.46)and(46.49±5.71)ng·L^(-1);the levels of IL-1βwere(59.87±0.83),(42.66±1.30),(48.37±3.34),(88.79±1.84)and(33.93±2.19)ng L^(-l);the levels of HYP were(24.79±0.82),(31.12±1.16),(25.83±1.12),(16.88±2.20)and(32.95±1.18)μg·mg^(-1);the levels of CAT were(24.99±1.47),(34.52±1.26),(31.00±1.15),(13.70±2.09)and(34.23±0.70)U·mg^(-1);the relative expression levels of TLR4 protein were 0.74±0.05,0.53±0.05,0.55±0.04,1.09±0.07 and 0.23±0.05;the relative expression levels of NF-κB protein were

关 键 词：大黄素 感染性创面 Toll样受体4/核因子κB信号通路 

分 类 号：R28[医药卫生—中药学]