International Journal of Biomedicine. 2018;8(4):342-346.
Originally published December 15, 2018
Background: Apoptosis, one of the most important mechanisms for maintaining homeostasis, is carried out under both physiological and pathological conditions. The aim of our study was to investigate the expression of markers of apoptosis through caspase-dependent and caspase-independent pathways during the reparative regeneration after serosal injuries of the peritoneum in the context of the prolonged p38 MAPK inhibition.
Methods: Peritoneal adhesions in the animal models were induced by a method developed by the authors that included opening the serous-muscular layer of the caecum with a 1cm cut followed by closing the wound with a Schmieden suture and scarifying a 1.5×1.5 cm area of the parietal peritoneum of the right lateral channel. Experiments were carried out on male 9-month-old Wistar rats. When closing the wound, control animals were intraperitoneally administered 3 mL of 0.9% sodium chloride solution (n=40) while experimental group rats were administered slow-release drug Seroguard® (Pharmasyntez JSC) (n=40). Animals were sacrificed within the period of 2 hours to 30 days post surgery. Expression of apoptosis markers was studied by immunohistochemical (Bcl-2, Bcl-x) and immunofluorescent (PARP-1) staining.
Results: It is interesting that, in cases of the natural regeneration of the peritoneal injury, expression of anti-apoptosis markers at the injury site came in two waves: it was the most pronounced on days 1–3 post surgery while the second peak of activity was observed on day 14. Within this time window, granulation tissue was actively growing and mature connective-tissue vascularized adhesions were being formed. By the end of the observation period (day 30), expression of anti-apoptosis proteins at the injury site became extremely low and a significant reduction in the amount of connective tissue cells was observed. It was found that a prolonged inhibition of the p38 activity resulted in a moderate increase in Bcl-2 expression on days 3–7, and a decrease in the activity on day 14 was followed by another increase in expression by day 30. The Bcl-xl expression was observed 12 hours to 3 days post surgery and then it went down to the minimum. Positive PARP-1 staining observed on days 3 to 30, which reached its maximum on day 14, was also typical of the experimental group.
Conclusion: The performed study demonstrated that a prolonged p38 MAPK inhibition in the adhesion formation models results in the activation of fibroblast apoptosis at the reparation site, which, in the authors’ opinion, predetermines a significant decrease in the adhesion formation in the experimental group.
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Received September 15, 2018.
Accepted October 22, 2018.
©2018 International Medical Research and Development Corporation.