PMID- 28585141 OWN - NLM STAT- MEDLINE DCOM- 20180316 LR - 20181113 IS - 1993-1352 (Electronic) IS - 1672-0733 (Linking) VI - 37 IP - 3 DP - 2017 Jun TI - Protective effects of hydrogen sulfide on portal hypertensive vasculopathy in rabbits by activating AKT-NF-kappaB pathway. PG - 348-351 LID - 10.1007/s11596-017-1738-4 [doi] AB - The role of hydrogen sulfide (H(2)S) 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 H(2)S levels, apoptosis of esophageal-gastric junction vascular smooth muscle cells, and the expression of nuclear transcription factor-kappaB (NF-kappaB), p-AKT, IkappaBa and Bcl-2 were detected. The cystathionine gamma lyase (cystathionine-gamma-splitting enzyme, CSE) in the junction vascular tissue was measured. The results showed that the plasma H(2)S levels and the CSE expression levels had statistically significant difference among different groups (P<0.05). As compared with PH group, plasma H(2)S 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-kappaB 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, IkappaBa 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, H(2)S 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-kappaB 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 IkappaBa 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. H(2)S can activate NF-kappaB by the p-AKT pathway, leading to the down-regulation of Bcl-2, eventually stimulating apoptosis of vascular smooth muscle cells, easing PH. H(2)S/CSE system may play an important role in remission of PH via the AKT-NF-kappaB pathway. FAU - Wang, Chao AU - Wang C AD - Department of Integrative Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Han, Juan AU - Han J AD - Department of Biliary and Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Li, Dong-Jian AU - Li DJ AD - Department of Integrative Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Yang, Zhen AU - Yang Z AD - Department of Integrative Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Zhang, Lin AU - Zhang L AD - Department of Breast and Thyroid Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zhanglinar@163.com. LA - eng PT - Journal Article DEP - 20170606 PL - China TA - J Huazhong Univ Sci Technolog Med Sci JT - Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban JID - 101169627 RN - 0 (Alkynes) RN - 0 (Antihypertensive Agents) RN - 0 (NF-kappa B) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 64165-64-6 (propargylglycine) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) RN - TE7660XO1C (Glycine) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Alkynes/pharmacology MH - Animals MH - Antihypertensive Agents/*pharmacology MH - Apoptosis/drug effects MH - Cystathionine gamma-Lyase/genetics/metabolism MH - Disease Models, Animal MH - Endothelial Cells/drug effects/metabolism/parasitology MH - Esophagus/blood supply/drug effects/pathology MH - Gene Expression Regulation MH - Glycine/analogs & derivatives/pharmacology MH - Hydrogen Sulfide/*pharmacology MH - Hypertension, Portal/complications/*drug therapy/genetics/parasitology MH - Intercellular Junctions/drug effects/metabolism/parasitology MH - Male MH - Muscle, Smooth, Vascular/drug effects/metabolism/parasitology MH - NF-KappaB Inhibitor alpha/genetics/metabolism MH - NF-kappa B/*agonists/genetics/metabolism MH - Portal System/drug effects/metabolism/parasitology MH - Proto-Oncogene Proteins c-akt/*agonists/genetics/metabolism MH - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism MH - Rabbits MH - Schistosoma japonicum/growth & development MH - Schistosomiasis japonica/complications/*drug therapy/genetics/parasitology MH - Signal Transduction MH - Stomach/blood supply/drug effects/pathology OTO - NOTNLM OT - apoptosis OT - hydrogen sulfide OT - portal hypertension OT - vascular smooth muscle EDAT- 2017/06/07 06:00 MHDA- 2018/03/17 06:00 CRDT- 2017/06/07 06:00 PHST- 2016/08/26 00:00 [received] PHST- 2017/05/01 00:00 [revised] PHST- 2017/06/07 06:00 [entrez] PHST- 2017/06/07 06:00 [pubmed] PHST- 2018/03/17 06:00 [medline] AID - 10.1007/s11596-017-1738-4 [pii] AID - 10.1007/s11596-017-1738-4 [doi] PST - ppublish SO - J Huazhong Univ Sci Technolog Med Sci. 2017 Jun;37(3):348-351. doi: 10.1007/s11596-017-1738-4. Epub 2017 Jun 6.