原儿茶酸对子宫内膜异位症大鼠炎症反应及血管生成的作用机制研究  

Study on the Mechanism of Effect of Protocatechuic Acid on Inflammatory Response and Angiogenesis in Rats with Endometriosis

作　　者：潘敏[1] 王晓莉[1] 胡婷[1] 付琼[1] 殷金凤[1] 黄超林 PAN Min;WANG Xiaoli;HU Ting(The Second People's Hospital of Chengdu,Sichuan Chengdu 610000,China)

机构地区：[1]四川省成都市第二人民医院,四川成都610000 [2]成都医学院第一附属医院,四川成都610000

出　　处：《河北医学》2023年第1期81-85,共5页Hebei Medicine

基　　金：四川省医学(青年创新)科研课题,(编号:Q20075)。

摘　　要：目的:观察原儿茶酸(Protocatechuic acid,PA)对大鼠子宫内膜异位症(heterotopia endometriosis,EMS)组织血管生成的作用及机制。方法:选择动情期雌性SD大鼠,通过子宫内膜自体缝合术建立SD大鼠的EMS疾病模型,将54只SD大鼠随机均分为空白组、模型组、PA(高、中、低)剂量组和孕三烯酮组,PA各剂量组和孕三烯酮组每天灌胃给药1次,模型组给予等容积的生理盐水,连续灌胃28d,空白组大鼠正常喂养。测量大鼠的异位组织体积,酶联免疫吸附(ELISA)法检测各组大鼠腹腔积液中肿瘤坏死因子α(TNF-α)、白介素6(IL-6)及白介素1β(IL-1β)水平,蛋白免疫印迹(Western blot)法检测组织中血管生成素(Ang)-1和Ang-2水平、血清及组织中血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)及基质金属蛋白酶9(MMP-9)含量、组织中总细胞外信号调节激酶1/2(t-ERK1/2)和磷酸化总细胞外信号调节激酶1/2(p-ERK1/2)的蛋白表达。结果:与空白组比较,模型组大鼠14d、42d的病灶体积升高,腹腔液炎症因子TNF-α、IL-6、IL-1β均显著升高,子宫内膜组织Ang-1、Ang-2蛋白表达均显著升高,血清中VEGF和MMP-2、MMP-9蛋白表达均显著升高,子宫内膜异位症组织中p-ERK1/2、VEGF、MMP-2和MMP-9的蛋白表达均显著升高(P<0.05)。原儿茶酸低剂量组、原儿茶酸中剂量组、原儿茶酸高剂量组呈浓度依赖性负向调控上述指标的变化(P<0.05)。结论:原儿茶酸可减轻子宫内膜异位症大鼠创面损伤,抑制炎症反应和血管生成,其潜在的机制可能与失活ERK/VEGF/MMP通路有关。Objective:To observe the effect and mechanism of protocatechuic acid(PA)on angiogenesis in rat endometriosis(EMS).Methods:Fifty-four female SD rats in estrus were selected to establish the EMS disease model by endometrial autograft and the rats were randomly divided into blank group,model group,PA(high,medium and low)dose group and gestrinone group.PA and gestrinone groups were administered gavage once a day.The model group was given the same volume of normal saline for 28 days.The rats in the blank group were fed normally.The ectopic tissue volume of rats was measured,and the tumor necrosis factor in the peritoneal fluid of rats in each group was detected by enzyme-linked immunosorbent assay(ELISA)α(TNF-α),Interleukin 6(IL-6)and interleukin 1β(IL-1β).The levels of angiopoietin(ANG)-1 and Ang-2,the contents of vascular endothelial growth factor(VEGF),matrix metalloproteinase 2(MMP-2)and matrix metalloproteinase 9(MMP-9)in serum and tissues,and the protein expression of total extracellular signal regulated kinase 1/2(t-ERK1/2)and phosphorylated total extracellular signal regulated kinase 1/2(p-ERK1/2)in tissues were detected by Western blot.Results:Compared with the blank group,the lesion volume increased at 14d and 42d,and the inflammatory factor TNF-α,IL-6,IL-1βand Ang-1 and Ang-2,VEGF,MMP-2 and MMP-9,p-ERK1/2,VEGF,MMP-2 and MMP-9 in endometriosis were all significantly increased in the model group rats(P<0.05).The changes of the above indexes were negatively regulated in a concentration dependent manner in the low-dose group,the middle dose group and the high-dose group of protocatechuic acid(P<0.05).Conclusion:Protocatechuic acid can reduce wound injury and inhibit inflammatory reaction and angiogenesis in rats with endometriosis.The underlying mechanism may be related to inactivation of ERK/VEGF/MMP pathway.

关 键 词：子宫内膜异位症 原儿茶酸 细胞外信号调节激酶-血管内皮生长因子-基质金属蛋白酶通路 

分 类 号：R711.71[医药卫生—妇产科学]