Effects of sodium hydrosulfide on HK2-NLRP3-GSDMD pathway and pyroptosis induced by lung ischemia/reperfusion in rats.

AIM: To investigate the effects of sodium hydrosulfide (NaHS) on hexokinase 2 (HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3 (NLRP3)-gasdermin D (GSDMD) pathway and pyroptosis induced by lung ischemia/reperfusion (I/R) in rats. METHODS: Male Sprague-Dawley rats were divided into 6 groups: control group, control+NaHS group, I/R group, low-dose NaHS+I/R (L+I/R) group, medium-dose NaHS+I/R (M+I/R) group, and high-dose NaHS+I/R (H+I/R) group, with 6 rats in each group. The NaHS was administered via intraperitoneal injection at 1.5 mL, 30 min before modeling. The left lung tissues were collected 30 min after ischemia and 1 h after reperfusion, and the wet/dry weight ratio and total lung water content were recorded. Hematoxylin-eosin (HE) staining was used to examine lung tissue morphological changes. The levels of malondialdehyde (MDA), myeloper oxidase (MPO) and lactate in lung tissues were measured with test kits. ELISA was employed to determine the levels of interleukin-1p (IL-1p) and IL-18. The expression of glycolysis- and pyroptosis-related indicators was analyzed by Western blot, qRT-PCR and immunofluorescence staining. RESULTS: Compared with control group, the rats in NaHS group showed no significant differences in all laboratory tests (P>0. 05). The rats in I/R group exhibited significant lung injury, oxidative stress, increased lactate level, and up-regulated glycolysis and pyroptosis (P<0. 05 or P<0. 01). Compared with I/R group, the indicators in L+I/R group showed a downward trend (P<0. 01) or no difference (P>0. 05), while those in M+I/R group displayed a significant reduction (P<0. 05 or P<0. 01). However, the indexes in H+I/R group exhibited no significant differences in these tests (all P>0. 05). CONCLUSION: A moderate dose (56 xmol"L-1-kg-1) of NaHS mitigated the occurrence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway, thus contributing to the attenuation of lung I/R injury in rats. [ABSTRACT FROM AUTHOR]