50 An et al.
Investigación Clínica 65(1): 2024
Folic acid, also known as vitamin M,
plays a crucial role in the synthesis of pro-
tein, nucleotide and pantothenic acid in
humans. It has been reported that a lack
of folic acid can lead to colitis and chronic
atrophic gastritis, which increases the risks
of gastrointestinal cancer 4. In addition, Lin
et al. 5 reported that the natural apoptosis
rate of gastric cancer cells was much high-
er in patients with gastric cancer given a
specific concentration of folic acid than in
those without intervention. Therefore, the
anti-cancer mechanism of folic acid may be
to regulate the expression of some cancer
cells to accelerate apoptosis.
The PI3K/AKT pathway is a signaling
pathway associated with proliferation, dif-
ferentiation and apoptosis, which regulates
the proliferation and survival of tumor cells
and plays an essential role in tumor cell mi-
gration and adhesion. It has been reported
that folic acid could produce positive effects
through the PI3K/AKT pathway in differ-
ent pathological conditions, such as colon
cancer, oral squamous cell carcinoma, and
so on6,7. Furthermore, folic acid could at-
tenuate the hypoxia-induced inflammatory
responses of THP-1 cells through inhibiting
the PI3K/Akt/HIF-1α pathway 8.
In this study, we aim to investigate the
effects of folic acid on chronic atrophic gas-
tritis rats through the PI3K/AKT pathway
and lay a preclinical foundation for folic acid
in treating CAG.
MATERIALS AND METHODS
Experimental materials
Animals: Specific Pathogen Free (SPF)
male Sprague Dawley (SD) rats, weighing
200-300g, purchased from the Guangzhou
University of Chinese Medicine Experimen-
tal Animal Center.
Reagents: MNNG (Guangzhou Kang-
ming Biotechnology Co., Ltd., batch number:
20210601), N1’-[2-[[5-[(dimethylamino)
methyl]-2-furanyl]methylthio]ethyl]-N1-
methyl-2-nitroethene-1,1-diamine (Guang-
dong Hengjian Pharmaceutical Co., Ltd.,
National Standard Word H44021173), ra-
nitidine (Guangdong Hengjian Pharmaceuti-
cal Co., Ltd., H44021173), folic acid tablets
(Fuzhou HAIWANGFU Pharmaceutical Co.,
Ltd., batch number: 21042810).
Materials and equipment: ELISA GAS
kit (Cat. MM-21284R1), MTweizL kit (Cat.
MM-0491R1), PI3K kit (Cat. MM-0427R1)
and Akt kit (Cat.MM-50624H1) were pur-
chased from Jiangsu enzyme-free Industry
Co., Ltd. (Yancheng, China), hematoxylin
and eosin staining solution (100ML, Bei-
jing Solebo Technology Co., Ltd., Beijing,
China). Semi-automatic rotary paraffin sec-
tioning machine (HM340E), Embedding
Workstation (Histosta), automatic dyeing
machine (Gemini AS), Rapid Tissue Pro-
cessor (STP120), refrigerated centrifuge
(FRESCO 70) and Multiskan SkyHigh Mi-
croplate Spectrophotometer (1510) were
purchased from Thermo Fisher Inc. (Massa-
chusetts, USA). Electric thermostatic drying
oven (Shanghai Jing Hong laboratory Instru-
ment Co.,Ltd., Shanghai, China), electronic
analytical balance (UX2200H, Shimatsu
Corporation, Tokyo, Japan), and optical mi-
croscope (CX-23, Olympus Corporation, To-
kyo, Japan).
Modeling and grouping
The model was established, and 30
SPF SD rats were randomly divided into
two groups. Ten rats were selected for nor-
mal feeding (NC Group), and the remaining
20 rats were used to establish the model.
MNNG-induced rats in the Model Group were
fed with 180 μg/mL MNNG and 0.003 g/mL
ranitidine hydrochloride once every three
days. At the same time, the rats in the blank
group were given the same amount of dis-
tilled water by gavage, and the other feeding
conditions were the same. Every six weeks,
one rat was selected from the blank group
and the model group for dissection, and
HE-stained sections were made to observe
the histomorphological changes of gastric
mucosa and test the effect of its modeling.