Abstract: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 1 β (IL-1 β). 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-1 β and 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.
潘敏, 王晓莉, 胡婷, 付琼, 殷金凤, 黄超林. 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[J]. 河北医学, 2023, 29(1): 81-85.
PAN Min, WANG Xiaoli, HU Ting, et al. Study on the Mechanism of Effect of Protocatechuic Acid on Inflammatory Response and Angiogenesis in Rats with Endometriosis. HeBei Med, 2023, 29(1): 81-85.
[1] Xiang Y,Wang G,Zhou L,et al.A systematic review and meta-analysis on transvaginal ultrasonography in the diagnosis of deep invasive endometriosis[J].Ann Palliat Med,2022,11(1):281-290. [2] Jan S,Morgan W,Tiffany A K,et al.Prevalence of endosalpingiosis and other benign gynecologic lesions[J].PLoS One,2020,15(5):e0232487. [3] Mishra A,Galvankar M,Vaidya S,et al.Mouse model for endometriosis is characterized by proliferation and inflammation but not epithelial-to-mesenchymal transition and fibrosis[J].Biosci,2020,45(1):105. [4] Signorile PG,Baldi A.Endometriosis:new concepts in the pathogenesis[J].Int Biochem Cell Biol,2010,42(6):778-780. [5] Galvankar M,Singh N,Modi D.Estrogen is essential but not sufficient to induce endometriosis[J].Biosci,2017,42(2):251-263. [6] Zhang J,Fu B,Chen X,et al.Protocatechuic acid attenuates anterior cruciate ligament transection-induced osteoarthritis by suppressing osteoclastogenesis[J].Exp Ther Med,2020,19(1):232-240. [7] Solomon EO,Isaac AA,Ebenezer OF,et al.Protocatechuic acid modulates reproductive dysfunction linked to furan exposure in rats[J].Toxicology,2020,442(9):152556. [8] 王金霞,崔宇红,成映霞,等.少腹逐瘀汤对子宫内膜异位症大鼠MAPK/ERK 信号通路的影响[J].中国病理生理杂志,2019,35(1):181-187. [9] Masella R,Santangelo C,D'Archivio M,et al.Protocatechuic acid and human disease prevention:biological activities and molecular mechanisms[J].Curr Med Chem,2012,19(18):2901-2917. [10] Zhang S,Gai Z,Gui T,et al.Antioxidant effects of protocatechuic acid and protocatechuic aldehyde:old wine in a new bottle[J].Evid Based Complement Alternat Med,2021,2021(11):6139308. [11] 张玉珠,于超,郑慧华,等.原儿茶酸对LPS诱导的小鼠子宫内膜炎的作用机制研究[J].中国畜牧兽医,2022,49(4):1585-1591. [12] Apte RS,Chen DS,Ferrara N.VEGF in signaling and disease:beyond discovery and development[J].Cell,2019,176(6):1248-1264. [13] Bassiouni W,Ali MAM,Schulz R.Multifunctional intracellular matrix metalloproteinases:implications in disease[J].FEBS,2021,288(24):7162-7182. [14] Zhou R,Yang X,Li X,et al.Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis[J].Neuroinflammation,2019,16(1):239. [15] 戴晓晓,陈秀秀.熊果酸对子宫内膜异位症模型大鼠内膜血管生成及ERK-VEGF/MMP-9通路的影响[J].中国药师,2019,22(12):2157-2162.