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. 2022 Jan 13:12:806012.
doi: 10.3389/fphar.2021.806012. eCollection 2021.

Effects of Exogenous Hydrogen Sulfide in the Hypothalamic Paraventricular Nucleus on Gastric Function in Rats

Chenyu Li  1   2 , Hongzhao Sun  1 , Yuan Shi  1 , Yan Yu  1 , Xiaofeng Ji  1 , Enguang Li  1 , Xiaofan Zhou  1 , Xiaomeng Liu  1 , Xikang Xue  1 , Haiji Sun  2
Affiliations

Effects of Exogenous Hydrogen Sulfide in the Hypothalamic Paraventricular Nucleus on Gastric Function in Rats

Chenyu Li et al. Front Pharmacol. .

Abstract

Background: Hydrogen sulfide (H2S) is a new type of gas neurotransmitter discovered in recent years. It plays an important role in various physiological activities. The hypothalamus paraventricular nucleus (PVN) is an important nucleus that regulates gastric function. This study aimed to clarify the role of H2S in the paraventricular nucleus of the hypothalamus on the gastric function of rats. Methods: An immunofluorescence histochemistry double-labelling technique was used to determine whether cystathionine-beta-synthase (CBS) and c-Fos neurons are involved in PVN stress. Through microinjection of different concentrations of NaHS, physiological saline (PS), D-2-Amino-5-phosphonovaleric acid (D-AP5), and pyrrolidine dithiocarbamate (PDTC), we observed gastric motility and gastric acid secretion. Results: c-Fos and CBS co-expressed the most positive neurons after 1 h of restraint and immersion, followed by 3 h, and the least was at 0 h. After injection of different concentrations of NaHS into the PVN, gastric motility and gastric acid secretion in rats were significantly inhibited and promoted, respectively (p < 0.01); however, injection of normal saline, D-AP5, and PDTC did not cause any significant change (p > 0.05). The suppressive effect of NaHS on gastrointestinal motility and the promotional effect of NaHS on gastric acid secretion could be prevented by D-AP5, a specific N-methyl-D-aspartic acid (NMDA) receptor antagonist, and PDTC, an NF-κB inhibitor. Conclusion: There are neurons co-expressing CBS and c-Fos in the PVN, and the injection of NaHS into the PVN can inhibit gastric motility and promote gastric acid secretion in rats. This effect may be mediated by NMDA receptors and the NF-κB signalling pathway.

Keywords: CBS (cystathionine β-lyase); gastric acid secretion; gastric motility; hydrogen sulfide; hypothalamic paraventricular nucleus (PVN).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Histological identification of microinjection, the location of the PVN in the brain. (A) A brain section stained with neutral red. The blue dot represents injection into the PVN. (B) The position of the PVN in the brain atlas.
FIGURE 2
FIGURE 2
The expression of CBS (green) and c-Fos (red) neurons at different time periods of RWIS. (A) The expression of CBS and c-Fos at 0 h of RWIS. (B) Enlarged picture of PVN of RWIS for 0 h. (C) Expression of CBS and c-Fos for 1 h of RWIS. (D) Enlarged picture of PVN of RWIS for 1 h. (E) Expression of CBS and c-Fos of restrained immersion for 3 h. (F) Enlarged picture of PVN of RWIS for 3 h.
FIGURE 3
FIGURE 3
The effect of microinjection of drugs in the PVN on gastric motility in rats. (A) The curve of rat gastric movement recorded under the dose of PVN microinjection of 2 nmol NaHS. (B) The curve of rat gastric movement recorded under the dose of PVN microinjection of 4 nmol NaHS. (C) The curve of rat gastric movement recorded under microinjection of 8 nmol NaHS. (D) The curve of rat gastric movement recorded under PVN microinjection of physiological saline.
FIGURE 4
FIGURE 4
Gastric motility data before and after microinjection of NaHS (2, 4, and 8 nmol) or saline (PS) into the PVN. (A) AACW, average amplitude contraction wave. (B) ADCW, average duration contraction wave. (C) Average gastric motility index. (D) Inhibition rate of AACW, ADCW, and average gastric motility index. **p < 0.01, after injection compared with before microinjection.
FIGURE 5
FIGURE 5
The effect of microinjection of 2 nmol NaHS and 2 nmol NaHS + PDTC into the PVN on gastric motility in rats. (A) Curve of gastric motility recorded in rats with 2 nmol NaHS + PDTC microinjection in PVN (B) Data of AACW. (C) Data of ADCW. (D) Data of mean gastric motility index. **p < 0.01, after injection compared with before microinjection.
FIGURE 6
FIGURE 6
The effect of microinjection of 2 nmol NaHS and 2 nmol NaHS + D-AP5 into the PVN on gastric motility in rats. (A) Curve of gastric motility recorded in rats with 2 nmol NaHS + D-AP5 microinjection in PVN (B) Data of AACW. (C) Data of ADCW. (D) Data of mean gastric motility index. **p < 0.01, after injection compared with before microinjection.
FIGURE 7
FIGURE 7
(A) The effect of PVN microinjection of 2, 4, 8 nmol NaHS and normal saline on gastric acid secretion. (B) The promotion rate of 2, 4, 8 nmol NaHS and PS on gastric acid secretion **p < 0.01, after injection compared with before microinjection.
FIGURE 8
FIGURE 8
The effect of microinjection of 2 nmol NaHS and 2 nmol NaHS + PDTC into the PVN on gastric acid secretion in rats. **p < 0.01, after injection compared with before microinjection.
FIGURE 9
FIGURE 9
The effect of microinjection of 2 nmol NaHS and 2 nmol NaHS + D-AP5 into the PVN on gastric acid secretion in rats. **p < 0.01, after injection compared with before microinjection.
FIGURE 10
FIGURE 10
Relationship between H2S and NMDA receptor/NF-κB pathway.
See this image and copyright information in PMC

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