Protective Effects of Hydrogen Sulfide on Portal Hypertensive Vasculopathy in Rabbits by Activating AKT-NF-κB Pathway / 华中科技大学学报（医学）（英德文版）

ABSTRACT

The role of hydrogen sulfide (H2S) in portal hypertension (PH)-induced esophagus-gastric junction vascular lesions in rabbits was observed.The rabbit PH models were established.The animals were randomly divided into the following groups:normal,PH,PH+sodium hydrosulfide (PH+S),PH+propargylglycine (PH+PPG).The plasma H2S levels,apoptosis of esophageal-gastric junction vascular smooth muscle cells,and the expression of nuclear transcription factor-κB (NF-κB),p-AKT,Iκ Ba and Bcl-2 were detected.The cystathionine γ lyase (cystathionine-gamma-splitting enzyme,CSE) in the junction vascular tissue was measured.The results showed that the plasma H2S levels and the CSE expression levels had statistically significant difference among different groups (P＜0.05).As compared with PH group,plasma H2S levels were declined obviously (11.9±4.2 vs.20.6±4.5,P＜0.05),and CSE expression levels in the junction vascular tissue were notably reduced (1.7±0.6 vs.2.8±0.8,P＜0.05),apoptosis rate of vascular smooth muscle cells per unit area was significantly decreased (0.10±0.15 vs.0.24±0.07,P＜0.05),and the expression levels of p-AKT and NF-κB were significantly decreased (2.31±0.33 vs.3.04±0.38,P＜0.05;0.33±0.17 vs.0.51±0.23,P＜0.05),however,Iκ Ba and Bcl-2 expression increased obviously (5.57±0.17 vs.3.67±0.13,P＜0.05;0.79±0.29 vs.0.44±0.36,P＜0.05) in PH+PPG group.As compared with PH group,H2S levels were notably increased (32.7±7.3 vs.20.6±4.5,P＜0.05),the CSE levels in the junction vascular tissue were significantly increased (6.3±0.7 vs.2.8±0.8,P＜0.05),apoptosis rate of vascular smooth muscle cells per unit area was significantly increased (0.35±0.14 vs.0.24±0.07,P＜0.05),and the expression levels of p-AKT and NF-κB were significantly increased (4.29±0.49 vs.3.04±0.38,P＜0.05;0.77±0.27 vs.0.51±0.23,P＜0.05),yet Iκ Ba and Bcl-2 expression decreased significantly (3.23±0.24 vs.3.67±0.13,P＜0.05;0.31±0.23 vs.0.48±0.34,P＜0.05) in PH+S group.It is concluded that esophagus-gastric junction vascular lesions happen under PH,and apoptosis of smooth muscle cells is declined.H2S can activate NF-κB by the p-AKT pathway,leading to the down-regulation of Bcl-2,eventually stimulating apoptosis of vascular smooth muscle cells,easing PH.H2S/CSE system may play an important role in remission of PH via the AKT-NF-κB pathway.