Biphasic Regulation of Apoptosis Following Gastric Irreversible Electroporation Using Tissue Immunohistochemistry of Activated Caspase-3 with TUNEL Method

Author:

Jeon Han Jo1ORCID,Chun Hoon Jai1,Choi Hyuk Soon1ORCID,Keum Bora1,Kim Hong Bae2ORCID,Kim Jong Hyuk3ORCID

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea

2. Department of Biosystems & Biomaterials Science and Engineering, Seoul National University, Seoul 08826, Republic of Korea

3. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA

Abstract

The regulation of apoptosis is the primary goal of ablation therapy. Irreversible electroporation (IRE) is a promising non-thermal tissue ablation-based therapy that induces apoptosis by manipulating electrical conditions. This study aimed to investigate IRE-induced gastric tissue apoptosis in response to changes in the electric field intensity, followed by the repair process. Among the 52 rats used in this study, 24 were used to explore apoptosis, and 28 were used to study regeneration. The apoptosis-to-necrosis ratio of the electrical field strength was evaluated using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3 immunohistochemistry. The size of IRE-induced ulcers in the gastric tissue continuously increased with increasing electrical intensity (r2 = 0.830, p < 0.001). The level of apoptosis gradually decreased after peaking at 200 V (1000 V/cm). The size of the 400 V-ablated ulcers continued to decrease, and they were not visible by day 14. The proliferation and migration of epithelial cells with fibroblasts were observed on day 3 and augmented on day 7 post-ablation. This investigation demonstrated the biphasic activation of apoptosis with respect to the electrical field strength. Visually and histologically, IRE-induced gastric ulcers demonstrated complete tissue regeneration after two weeks.

Funder

Korean government

Publisher

MDPI AG

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