H₂S Attenuates Myocardial Injury In Septic Rats Through Inhibition Of PERK-eIF2α Pathway

Objective: Based on the "PERK-EIF2α-CHOP pathway in endoplasmic reticulum stress",this study investigated the potential role of exogenous hydrogen sulfide in myocardial injury in a rat model of sepsis and whether it plays a regulatory role in myocardial injury in sepsis by attenuating the PERK-EIF2α-CHOP pathway in endoplasmic reticulum stress.Methods: SD rats(males,84 in total)were divided by randomization into 7 groups: sham-operated group with sutures after open abdomen only(Sham group),sham-operated + sodium thiodicarbonate group with sutures after open abdomen injected with sodium thiodicarbonate(Sham+Na HS group),sham-operated +endogenous H2 S inhibitor group with sutures after open abdomen injected with sodium thiodicarbonate(Sham+PAG group),sepsis group with perforated cecum ligation after open abdomen(CLP group),sepsis+ sodium thioredoxin-treated group(CLP + Na HS group),sepsis + endogenous H2 S inhibitor-treated group(CLP + PAG group),and sepsis + sodium thioredoxin + endogenous H2 S inhibitor-treated group(CLP +Na HS + PAG group),were taken at 12 h hours.The levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-2(IL-2),interleukin-6(IL-6)and interleukin-10(IL-10)in rat serum were measured by ELISA kits,and pathological HE staining(hematoxylin-The extent of myocardial injury was monitored by hematoxylin-eosin(HE)staining;the apoptosis rate of myocardial cells in each group was measured by apoptosis kit;the expression of PERK,e IF2α,p-PERK,p-e IF2α,GRP78,ATF4 and CHOP in myocardial tissues of each group was detected by protein immunoblotting technique.Results:(1)Sham group,Sham+Na HS group and Sham+PAG group in the sham-operated group,and there were no statistical differences in the detection indexes of these three groups.(2)Compared with the Sham group,myocardial injury markers CK-MB and c Tn I were significantly higher and pathological injury was more severe in the CLP group,and TNF-α,IL-2,IL-6 and IL-10 among serum inflammatory factors were significantly higher and statistically significant in rats.(3)Compared with CLP group,myocardial injury markers CK-MB and c Tn I levels were significantly lower in CLP+Na HS group,pathological injury in pathological HE sections was less severe,TNF-α,IL-2,IL-6 levels in serum inflammatory factors were lower and IL-10 levels were higher in rats with statistical significance.(4)Compared with the Sham group,the protein expression of p-PERK,p-EIF2α,ATF4,CHOP,and GRP78 were significantly higher in the CLP group,and there was more apoptosis in cardiac myocytes.(5)The protein expressions of p-PERK,p-EIF2α,ATF4,CHOP,and GRP78 were decreased in the CLP+Na HS group compared with the CLP group.Conclusion: Exogenous H2 S reduced myocardial cell apoptosis in septic rats by inhibiting the PERK-e IF2αsignaling pathway,thereby reducing myocardial injury and protecting myocardial tissue function.