[Protective effect of hydrogen sulfide on intestinal ischemia/reperfusion injury in rats by regulating c-Jun N-terminal kinase/activator protein-1 signaling pathway].

Objective: To investigate whether hydrogen sulfide (H₂S) protects against intestinal ischemia/reperfusion (I/R) injury in rats by regulating c-Jun N-terminal kinase/activator protein-1 (JNK/AP-1) signaling pathway.

Methods: Thirty male Wistar rats were divided into sham operated group (Sham group), I/R group, and H₂S donor sodium hydrosulfide (NaHS) intervention group (I/R+NaHS group), with 10 rats in each group. The I/R injury model was established by blocking the superior mesenteric artery with a non-traumatic vascular clip, with 60 minutes of ischemia followed by 120 minutes of reperfusion. In the I/R+NaHS group, 100 μmol/kg of NaHS was injected through the tail vein 10 minutes before reperfusion, followed by continuous infusion of 1.07 mmol×kg^-1×h^-1 until the end of the 120-minute reperfusion period. Plasma H₂S concentration was measured using a sensitive sulfur electrode. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the small intestine tissue were assayed spectrophotometrically. Histological sections of the small intestine were stained with hematoxylin-eosin (HE) staining and scored using the Chiu scoring system to assess the degree of intestinal mucosal injury. Western blotting was used to detect the protein expressions of phosphated-JNK (p-JNK), JNK, AP-1, and BCL-2 in the small intestine tissue.

Results: Compared with the Sham group, the I/R group exhibited damage to the lamina propria, hemorrhage, and ulceration, with a significantly higher Chiu score (4.80±0.63 vs. 0.70±0.09, P < 0.01); plasma H₂S concentration and SOD activity in the ileum tissue were significantly reduced [H₂S (μmol/L): 17.29±1.40 vs. 34.62±1.48, SOD (kU/g): 5.38±0.93 vs. 20.56±1.85, both P < 0.01], while MDA level was significantly elevated (μmol/g: 16.06±1.71 vs. 4.80±0.92, P < 0.01); expression of BCL-2 protein in the ileum tissue was significantly down-regulated (BCL-2/β-actin: 0.32±0.06 vs. 0.79±0.05, P < 0.01), while expressions of p-JNK and AP-1 proteins were significantly up-regulated (p-JNK/β-actin: 0.69±0.03 vs. 0.10±0.03, AP-1/β-actin: 0.82±0.02 vs. 0.22±0.02, both P < 0.01). Compared with the I/R group, the I/R+NaHS group showed moderate separation between the epithelial and lamina propria layers, with partial damage to the tips of the villi; the Chiu score was significantly lower (2.90±0.56 vs. 4.80±0.63, P < 0.01); plasma H₂S concentration and SOD activity in the ileum tissue were significantly increased [H₂S (μmol/L): 24.48±1.84 vs. 17.29±1.40, SOD (kU/g): 10.29±1.26 vs. 5.38±0.93, both P < 0.01], while MDA level was significantly reduced (μmol/g: 7.88±1.01 vs. 16.06±1.71, P < 0.01); expression of BCL-2 protein in the ileum tissue was significantly up-regulated (BCL-2/β-actin: 0.44±0.06 vs. 0.32±0.06, P < 0.01), while expressions of p-JNK and AP-1 proteins were significantly down-regulated (p-JNK/β-actin: 0.54±0.05 vs. 0.69±0.03, AP-1/β-actin: 0.66±0.04 vs. 0.82±0.02, both P < 0.01). There was no statistically significant difference in the expression of JNK in the ileum tissue among the Sham group, I/R group, and I/R+NaHS group (JNK/β-actin: 0.63±0.02, 0.66±0.02, 0.64±0.02, respectively, P > 0.05).

Conclusions: H₂S exerts a protective effect on intestinal I/R injury in rats by down-regulate the expression of the JNK/AP-1 signaling pathway, as well as reducing oxidative stress levels.