J Korean Med Sci.  2017 Feb;32(2):186-194. 10.3346/jkms.2017.32.2.186.

Enhancement of Gastric Ulcer Healing and Angiogenesis by Hepatocyte Growth Factor Gene Mediated by Attenuated Salmonella in Rats

Affiliations
  • 1Department of Clinical Laboratory Medicine, Lanzhou General Hospital of Lanzhou Military Region, People's Liberation Army, Key Laboratory of Stem Cell and Gene Drug in Gansu Province, Lanzhou, China. haxiaoqin2013@163.com

Abstract

The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 10⁹ cfu), vehicle (TP, 1 × 10⁹ cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm², which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm², respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm², which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site.

Keyword

Gastric Ulcer; Hepatocyte Growth Factor; Salmonella typhimurium; Gene Therapy; Wistar Rat

MeSH Terms

Acetic Acid
Animals
Epithelial Cells
Genetic Therapy
Granulation Tissue
Hepatocyte Growth Factor*
Hepatocytes*
Microvessels
Models, Animal
Rats*
Salmonella typhimurium
Salmonella*
Sodium Bicarbonate
Stomach Ulcer*
Ulcer
Acetic Acid
Hepatocyte Growth Factor
Sodium Bicarbonate
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