The Neuroendocrinal Modulating Mechanism Of Gaseous Signaling Molecule Hydrogen Sulfide In Sepsis

Sepsis was defined as infection plus systemic inflammatory response syndrome. Sepsis can progress to severe sepsis or septic shock. Sepsis is primary death reason of patients in ICU. The mechanism of sepsis has not been clarified completely and can’t be cured effectively. Hydrogen sulfide（H₂S）which can be produced endogenously is a new signal molecular found recent year. H₂ S involve in pathology of many diseases contain sepsis.This study contain two parts:1. Effects of hydrogen sulfide on rats serum electrolytes and renal function during sepsis.Objective To investigate effects of hydrogen sulfide（H₂S） on septic rats serum electrolytes and renal function.Methods Ninety-two female SD rats,twenty rats were randomly divided into 5 groups: normal rats group, sepsis 6h、12h、24h group（n=5/group）. Seventy-two rats randomly divided into 4 groups（n=18/group）: negative contrast group, sepsis +saline group, sepsis + sodium hydrosulfide（NaHS） group, sepsis +propargylglycine（PAG） group. Rats were administrated saline, NaHS, PAG respectively by peritoneal injection 1h before operation. Rats were sacrificed at designated time and serum was collected for detecting serum electrolytes, creatinine（Cr） and urea nitrogen（BUN） concentrations.Results Septic rats serum Na+ level increased followed by a decline, then returned to normal level after CLP. Serum Cl- level increased after sepsis till 6h. After 6h, serum Cl- level started to decline in a time-depended manner. Serum K+, Cr and BUN levels increased in a time-depended manner after sepsis. Serum Ca2+ level decreased at all time points after sepsis. Compared with sepsis + saline group, serum Na+, Cl-, K+, Cr and BUN levels were significantly decreased in sepsis + NaHS group（P <0.05）. There was no effect on serum Ca2+ level at all time points（P >0.05）. At all time points in sepsis +PAG group, Serum Na+, Cl-, K+,Cr and BUN levels were significantly elevated（P <0.05） and serum Ca2+ level do not significantly changed（P >0.05）.Conclusion Sepsis induce serum electrolytes disturbance. Renal function is injured at early phase of sepsis and deteriorates in a time-depended manner. H₂ S may regulate serum electrolyte concentrations through effecting on renal function during sepsis.2. Effects of hydrogen sulfide on septic rats Hypothalamic-Pituitary-Adrenal axis response.Objective To investigate the effects of H₂ S on serum corticosterone（CORT）, adrenocorticotropin（ACTH） and hypothalamic corticosterone（CRH） concentration in septic rats.Methods Sepsis was induced in adult male Sprague-Dawley（SD） rats by cecal CLP. Sixty-three rats were randomly divided into nine groups（n=7/group）: negative contrast group; sepsis 6h, 12 h, 24 h groups; sepsis 12h+ NaHS; sepsis 12h+ hydroxylamine（HA）+ propargylglycine（PAG） group; sepsis 12h+ HA group; sepsis 12h+ PAG group. Some septic rats were sacrificed at 6h, 12 h, 24 h after CLP. Others received intraperitoneal injection of different drugs 1h before CLP and were sacrificed at 12 h after CLP. The samples of serum or hypothalamus were collected. Serum CORT, ACTH and hypothalamic CRH concentration were detected by enzyme-linked immunosorbent assay（ELISA）.Results 1.Serum CORT, ACTH and hypothalamic CRH concentrations increased significantly 6h,12 h,24h after model making（P <0.05）. Serum CORT, ACTH and hypothalamic CRH concentrations were significantly higher 12 h,24h after CLP than that of 6h after CLP（P<0.05）. Serum CORT concentration at 24 h after CLP was significantly higher than that at 12 h after CLP（P<0.05）, serum ACTH concentration was significantly lower than that at 24 h after CLP（P <0.05）. 2. Inhibition of central or peripheral H₂ S generation increased serum CORT, ACTH and hypothalamic CRH concentrations（P<0.05）. Inhibition of the production of central H₂ S increased serum CORT, ACTH and hypothalamic CRH concentration（P<0.05）. Inhibition of the production of peripheral H₂ S increased serum CORT concentration（P<0.05）and decreased hypothalamic CRH concentration（P<0.05）. Serum ACTH concentration did not significantly changed（P <0.05）.Conclusion: HPA axis is active during sepsis; H₂ S inhibit HPA axis response by central and peripheral mechanism during sepsis.