Izražanje matriksne metaloproteinaze 1 in 2 ter ciklooksigenaze 2 pri celjenju venske golenje razjede

Bergant Suhodolčan, Aleksandra (author), Luzar, Boštjan (mentor)

Venska golenja razjeda nastane v zadnji fazi kroničnega venskega popuščanja. V 24 tednih se zaceli 50–80 % venskih razjed. Pri upočasnjenem celjenju imajo ključno vlogo dejavniki kroničnega vnetja. Pomemben dejavnik so matriksne metaloproteinaze (MMP), ki so vključene v patofiziološki proces celjenja VGR. Ciklooksigenaza 2 (COX-2) sodeluje v sintezi prostanoidov in se tvori ob vnetju. V raziskavo smo vključili 22 odraslih bolnikov z 29 razjedami in jih spremljali 24 tednov. Venske golenje razjede smo ob vključitvi in po 4 tednih izmerili s tridimenzionalnim laserskim merilnikom ter odvzeli biopsijo razjed in zdravega tkiva. Iz meritev smo za vsako razjedo izračunali horizontalno in vertikalno začetno hitrost celjenja razjed . Izražanje MMP-1, MMP-2 in COX-2 smo v biopsijah razjed prikazali z imunohistokemično metodo. Namen našega raziskovalnega dela je bila primerjava izražanja aktivnih oblik MMP-1, MMP-2 in COX-2 v tkivu venskih razjed ter v zdravi koži in spremljanje njihove dinamike v procesu celjenja. Razjede smo glede na to, ali so bile po 24 tednih zaceljene ali ne, razdelili v dve skupini. Primerjali smo izražanje MMP-1, MMP-2 in COX-2 v parnih biopsijah razjed ob vključitvi in po 4 tednih. Ugotavljali smo vlogo MMP-1, MMP-2 in COX-2 v prvih 4 tednih opazovanja pri obeh hitrostih celjenja in pri dokončni zacelitvi v 24 tednih. Horizontalna začetna hitrost celjenja (p = 0,027), vertikalna začetna hitrost celjenja (p = 0,031) in predhodno trajanje razjede (p = 0,034) so pomembni napovedni dejavniki za zacelitev v 24 tednih. Pri skupini zaceljenih razjed je upad MMP-1 v 4 tednih statistično pomemben (p = 0,03). Kot prvi smo pokazali obratno povezavo med MMP-2 in horizontalno hitrostjo celjenja razjede (p = 0,041). Znižanji MMP-1 in MMP-2 v prvih 4 tednih sta se pokazali kot pomembna napovedna dejavnika zacelitve venske golenje razjede. Dokazali smo, da je verjetnost zacelitve pri razjedah, pri katerih se je izražanje MMP-1 v 4 tednih znižalo, višja za 3,7-krat, medtem ko je verjetnost zacelitve ob znižanju MMP-2 višja za 2,1-krat. Z rezultati naše raziskave smo dokazali pomen aktivne oblike MMP v tkivu v procesu celjenja venskih golenjih razjed. Upad MMP-1 in MMP-2, ne pa tudi COX-2, v biopsijah razjed v 4 tednih opazovanja napoveduje ugodno celjenje venskih golenjih razjed.

• Language: Slovenian
• Keywords: kronična venska bolezen, venska golenja razjeda, matriksne metaloproteinaze, ciklooksigenaza, začetne hitrosti celjenja, celjenje ran
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2022
• PID: 20.500.12556/RUL-148940
• Publication date in RUL: 01.09.2023

Secondary language

• Language: English
• Title: Expression of matrix metalloproteinase 1, 2 and cyclooxygenase 2 in healing of venous leg ulcers

Abstract

Chronic venous ulcers represent the last stage of chronic venous insufficiency. As reported, about 50-80% of chronic venous ulcers heal in 24 weeks. Chronic inflammation appears to be the most important reason for prolonged healing. Matrix metalloproteinases (MMPs) are involved in the pathophysiology of chronic venous ulcer healing. Cyclooxygenase-2 (COX-2) is an important enzyme in prostanoid synthesis, which is induced during inflammation. 29 venous ulcers in 22 patients were included in the study and observed for 24 weeks. All ulcers were measured at enrolment and after 4 weeks, using laser triangulation, and biopsy of the ulcer tissue and healthy skin was performed. Horizontal and vertical initial healing rates were calculated using laser measurements. Expression of MMP-1, MMP-2 and COX-2 was assessed in biopsy samples using immunohistochemistry. The first aim of our study was to compare the expression of MMP-1, MMP-2 and COX-2 in wound tissue to that in normal skin. The second aim was to observe the expression of the above factors at the beginning and 4 weeks later, in relation to healing rates and final healing outcome after 24 weeks. The enrolled population was divided into two groups, namely healed and non-healed wounds after 24 weeks. Horizontal initial healing rates (p=0.027) and vertical initial healing rates (p=0.031) in the first 4 weeks, as well as previous ulcer duration (p=0.034), proved to be an important predictive factor of healing in 24 weeks. In the healed group, MMP-1 decrease in the first 4 weeks was statistically significant (p=0.03). Decreases in MMP-1 and MMP-2 after 4 weeks of observation were distinct, positive predictors for ulcer healing. The healing odds were 3.7 times higher for a decrease in MMP-1 and 2.1 times higher for a decrease in MMP-2, compared to the healing odds for a non-decrease in MMP-1 and MMP-2. In conclusion, a decrease in active form of MMP-1 and MMP-2, but not COX-2, in wound biopsy samples after 4 weeks of observation can predict better healing of chronic venous ulcers.

• Keywords: chronic venous disease, chronic venous ulcer, matrix metalloproteinase, cyclooxygenase, initial healing rates, wound healing