Effect of the p38 MAPK Inhibitor on the Expression of Metalloproteinases and Their Inhibitors during the Formation of Abdominal Adhesions

Abstract

Background: The aim of this study was to assess the effect of blockade of the p38 mitogen-activated protein kinase (MAPK) on the expression of genes encoding metalloproteinases (MMPs) during the formation of adhesions in the abdominal cavity. Methods and Results: The experiments were carried out on male Wistar rats (n=75). The studies were carried out in two groups: Group 1 (control, n=35) – modelling the adhesive process; Group 2 (experimental, n=35) – modelling the adhesive process with intraperitoneal administration of Seroguard®—a prolonged form of the p38 MAPK inhibitor. The expression of the MMP1a, MMP2, MMP7, MMP9, and TIMP genes was assessed using real-time PCR. In the control group, overexpression of the MMP1a and MMP7 genes began from 6 hours after modeling the adhesive process, MMP9 – from Day 1, MMP2 – from Day 7 and persisted until the end of observation. With local blockade of p38 MAPK, the level of overexpression of genes encoding MMPs in the early stages was higher than in the control group (MMP1a – by Day 1; MMP7 – by 6 hours and Day 1, MMP9 – by 12 hours). From Day 3 to Day 14, the MMP1a and MMP7 expression in the experimental group was significantly lower than in the control group. Conclusion: The performed study demonstrated the involvement of different types of MMPs—collagenases (MMP1a), gelatinases (MMP2 and 9), matrilysins (MMP7)—in the rearrangement of the extracellular matrix during the process of adhesion formation in the abdominal cavity.

Umurtqalararo Disk Churralarida Toʻqimali Metalloproteinaza (Mmp-1, MMP-8, MMP-9) Va Uning Ingibitorlari (Mpti-1) Darajasiga Papaya Preparatlarining Taʼsiri

“…Oʻzining fermentativ faolligi natijasida, ular hujayradan tashqari matriks oqsillarining barcha turlarini parchalash qobiliyatiga ega boʻlib, shu tariqa toʻqimalarning remodellanishida, hujayralar angiogenezida, proliferatsiyasida, migratsiyasida va differentsiatsiyasida, apoptoz mexanizmlarida, shuningdek, oʻsmalarning oʻsishini toʻhtatishda oʻz vazifasini bajaradi. Shuningdek, ular membranali retseptorlarni parchalashda, apoptoz ligandlarning chiqarilishida hamda hemokinlar va sitokinlarning faollashuvi va deaktivatsiyasida ishtirok etadi [14]. Neytrofilli kollagenaza MMP-8 hamda jelatinaza -MMP-9 sifatida belgilangan [9].…”