祛腐生肌外治法对糖尿病溃疡大鼠血管内皮细胞生长因子(VEGF)及其相关信号通路影响的meta分析和系统评价  

Meta-analysis and Systematic Review of the Effect of External Therapy by Slough-Removing and Tissue Regeneration-Promoting Method of on Vascular Endothelial Growth Factor(VEGF)and its Related Signaling Pathways in Diabetic Ulcer Rats

作　　者：蒋立新[1] 朱思洵 JING Lixin;ZHU Sixun(Jiangyin Hospital of Traditional Chinese Medicine,Jiangsu Wuxi 214400,China;Nanjing University of Traditional Chinese Medicine,Jiangsu Nanjing 210023,China)

机构地区：[1]江苏省江阴市中医院,江苏无锡214400 [2]南京中医药大学,江苏南京210023

出　　处：《中医药临床杂志》2023年第8期1548-1559,共12页Clinical Journal of Traditional Chinese Medicine

基　　金：江阴市卫建委项目(G202007)。

摘　　要：目的:系统评价中药外用祛腐生肌法对糖尿足溃疡(DFU)大鼠模型血管内皮细胞生长因子(VEGF)及其相关信号通路的影响并进行Meta分析。方法:在中国知网、万方、PubMed等数据库进行文献检索,检索时间自建库至2022年4月。根据SYRCLE的偏倚风险工具对每一篇纳入文献的研究质量进行评价。使用Review Manager 5.4.1软件根据Cochrane系统评价方法进行Meta分析。结果:包括508只大鼠的19项研究,纳入研究的质量分数都在3~5分。Meta分析结果显示,无论是促进糖尿病溃疡大鼠创面组织中VEGF蛋白表达、增加创面组织中VEGF mRNA水平还是提高大鼠血清中VEFG因子含量,与对照组相比,祛腐生肌治疗组都具有明显的优势[SMD=1.39,95%CI(0.67,2.10),P=0.0002;SMD=5.53,95%CI(0.58,10.11),P=0.03;SMD=1.91,95%CI(0.73,3.09),P=0.002]。亚组分析显示,当对照组为常规换药组时,中药外用促进创面组织中VEGF蛋白表达的优势明显[SMD=2.02,95%CI(1.27,2.78),P=0.0002;SMD=2.06,95%CI(0.16,3.96),P=0.03],当对照组为生长因子换药组时,尚不能证明二者在促进创面组织中VEGF蛋白表达方面有差异[SMD=0.04,95%CI(-0.52,0.61),P=0.88]。同时研究表明,中药外用可能是通过调控HIF-1/VEGF/VEGFR-2信号通路、PI3K/AKT信号通路、Wnt/β-catenin信号通路中的上下游分子的表达,从而影响尿病溃疡大鼠创面组织及血清中VEGF的表达水平,这些分子包括HIF-1α[SMD=2.35,95%CI(1.11,3.59),P=0.0002]、VEGFR-2[SMD=4.52,95%CI(0.63,8.42),P=0.02]、PI3K[SMD=-0.94,95%CI(-1.08,-0.80),P=0.00001]、AKT[SMD=0.28,95%CI(0.22,0.34),P<0.00001]、β-catenin[SMD=0.23,95%CI(0.19,0.27),P<0.00001]、GS3K-β[SMD=0.44,95%CI(0.06,0.82),P=0.02]、Cym-c[SMD=-0.47,95%CI(-0.72,-0.22),P=0.0002]。结论:中药外用祛腐生肌法治疗DFU大鼠创面与其促进VEGF在创面和血清中的表达相关,其机理可能与影响HIF-1α/VEGF/VEGFR-2、Wnt/β-catenin、PI3K/AKT等信号通路的上下游分子有关,但仍需更多的大样本、�Objective:To systematically evaluate the effect of external application of traditional Chinese medicine on vascular endothelial growth factor(VEGF)and its related signaling pathways in diabetic foot ulcer(DFU)rat model and conduct Meta-analysis.Methods:Literature search was carried out in China National Knowledge Network,Wanfang,PubMed and other databases,and the retrieval time was from the establishment of the database to April 2022.The study quality of each included article was assessed according to SYRCLE’s risk of bias tool.Meta-analysis was performed according to the Cochrane systematic review method using Review Manager 5.4.1 software.Results:19 studies including 508 rats were included,and the quality scores of the included studies were all between 3 and 5 points.The results of Meta-analysis showed that,compared with the control group,the treatment group for removing putrefaction and promoting muscle growth had a significant effect on promoting the expression of VEGF protein in the wound tissue of diabetic ulcer rats,increasing the level of VEGF mRNA in the wound tissue,and increasing the level of VEFG factor in rat serum.[SMD=1.39,95%CI(0.67,2.10),P=0.0002;SMD=5.53,95%CI(0.58,10.11),P=0.03;SM=1.91,95%CI(0.73,3.09),P=0.002].Subgroup analysis showed that when the control group was the routine dressing group,external application of traditional Chinese medicine had a significant advantage in promoting the expression of VEGF protein in wound tissue[SMD=2.02,95%CI(1.27,2.78),P=0.0002;SMD=2.06,95%CI(0.16,3.96),P=0.03],when the control group was the growth factor dressing group,there was no difference in promoting the expression of VEGF protein in wound tissue[SMD=0.04,95%CI(-0.52,0.61),P=0.88].At the same time,studies have shown that external use of traditional Chinese medicine may affect the expression of upstream and downstream molecules in the HIF-1/VEGF/VEGFR-2 signaling pathway,PI3K/AKT signaling pathway,and Wnt/β-catenin signaling pathway,thereby affecting the diabetic ulcer rats.The expression levels of

关 键 词：祛腐生肌法 糖尿病足溃疡(DFU) 大鼠模型 血管内皮生长因子(VEGF) HIF-1/VEGF/VEGFR-2信号通路 PI3K/AKT信号通路、Wnt/β-catenin通路 META分析 

分 类 号：R596.1[医药卫生—内科学]