Study On The Effect Of Hydrogen Sulfide On Portal Hypertension

Aims: In the present study, we have investigated the impact of endogenous hydrogen sulfide (H2S) in portal hypertension rats. What's more, the possible impact of hydrogen sulfide donor—sodium hydrosulfide (NaSH) on experimental portal hypertension (PH) induced by partly portal vein ligation, the impacts of it on endogenous nitric oxide/ nitric oxide synthase (NO/NOS) pathway and carbon monoxide/ heme oxygenase (CO/HO) pathway were detected, in order to explore the possible mechanisms.Methods:⑴Twenty male SD rats were randomly divided into three groups: control group, sham group undergoing sham operation and the group undergoing the operation of partly portal vein ligation (PPVL). Fourteen days later, portal venous pressure (PVP) and systemic mean arterial pressure (MAP) were measured. The expressions of cystathionine-γ-lyase (CSE) protein in liver and smooth muscle of portal vein were determined by immunohistochemistry. The expression of CSEmRNA in liver was determined by RT-PCR.⑵Thirty male SD rats were randomly divided into PPVL group (n=10), PPVL+ NaSH group (n=10), sham group (n=5) and control group (n=5). Rats in PPVL group and PPVL+ NaSH group were subjected to the operation of partly portal vein ligation to create an animal model of portal hypertension. 14 days later, portal venous pressure (PVP) and systemic mean arterial pressure (MAP) were measured. The expression of nitric oxide synthase (NOS2, NOS3) protein and that of heme oxygenase (HO-1, HO-2 ) protein in hepatic cells were determined by immunohistochemistry, the expression of NOS mRNA and that of HOmRNA were determined by RT-PCR.Results:⑴The PVP in PPVL group was remarkably increased compared with that in other groups, while the MAP was decreased (p<0.01). And the expression of CSE protein in liver and smooth muscle of portal vein was increased (p<0.05), the expression of CSEmRNA in liver was prominently increased (p<0.01). There was no difference between control group and sham group.⑵There was no difference between control group and sham group, and we didn't find the expression of NOS2 protein and that of NOS2 mRNA. Compared the PPVL group with the sham group, we can find that the PVP in PPVL group was increased (p<0.05), while the MAP was decreased (p<0.05). And the PVP in the PPVL + NaSH group was increased compared with that in the PPVL group (p<0.05), the MAP was decreased too (p<0.05). We found that the expression of NOS2 protein and that of NOS2 mRNA in both the PPVL group and the PPVL + NaSH group, and the expression of them were decreased in the latter group (p<0.05). Among four groups, the expression of NOS3 protein and that of NOS3 mRNA were not changed. Compared the PPVL group with the sham group, the expression of HO-1 protein was increased in the PPVL group(p<0.05), the expression of HO-1 mRNA was increased too (p<0.01); but the expression of HO-2 protein and that of HO-2 mRNA was not changed. Compared the PPVL+ NaSH group with the PPVL group, the same result occurred.Conclusion:⑴The endogenous H2S system may play an important role in the formation and maintenance of portal hypertension.⑵NaSH might promote portal hypertension induced by partly portal vein ligation, and its mechanism might be associated with the changes in endogenous NO/NOS2 pathway and CO/HO-1 pathway, but not NO/NOS3 pathway or CO/HO-2 pathway.