title: [Effects of hydrogen sulfide on vascular inflammation in pulmonary hypertension induced by high pulmonary blood flow: experiment with rats].
abstract: OBJECTIVE
  To investigate the effects of hydrogen sulfide (H2S) on vascular inflammation in pulmonary hypertension induced by high pulmonary blood flow.
  
  
  METHODS
  Forty-four male SD rats were randomly divided into 8 groups: 4-week control group (n = 7), 4-week shunt group (n = 7), 4-week shunt + propargylglycine (PPG, an endogenous H2S release inhibitor) intraperitoneal injection group (n = 8), 11-week control group (n = 7), 11-week shunt group (n = 7), and 11-week shunt + sodium hydrosulfide (NaHS, a H2S donor) intraperitoneal injection group (n = 8). Right ventricular catheterization was used to measure the mean pulmonary arterial pressure (mPAP). Immunohistochemistry was used to detect the expression of inflammatory related factor intercellular adhesion molecule-1 (ICAM-1), and the key molecules of nuclear factor-kappaB (NF-kappaB) signal transduction pathway, including NF-kappaB p65 and inhibitor of NF-kappaB (IkappaBalpha), in the pulmonary artery, and ELISA was used to detect the concentrations of the inflammatory related factors, including ICAM-1, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in blood plasma and lung tissues so as to reflect the corresponding inflammatory responsiveness.
  
  
  RESULTS
  The plasma and lung tissue ICAM-1, IL-8 and MCP-1 contents of the 4-week shunt group were all significantly higher than those of the 4-week control group (P < 0.05 or P < 0.01). The mPAP of the 4 week shunt + PPG group was (20.3 +/- 1.7) mm Hg, significantly higher than that of the 4-week shunt group [(16.2 +/- 1.5) mm Hg, P < 0.01]. The expression levels of ICAM-1 and NF-kappaB p65 in the small and median pulmonary artery endothelin cells of the 4-week shunt + PPG group were both significantly stronger than those of the 4-week shunt group (P < 0.05 or P < 0.01), whereas the expression of IkappaBalpha was weaker than that of the 4-week shunt group (P < 0.05). The plasma IL-8 content of the 4-week shunt + PPG group was (148 +/- 29) micromol/L, significantly higher than that of the 4 week-shunt group [(118 +/- 23) micromol/L, P < 0.05], and the lung tissue ICAM-1 and MCP-1 levels of the 4-week shunt + PPG group were (27.3 +/- 5.0) micromol/g and (12.9 +/- 1.1) micromol/g respectively, both significantly higher than those of the 4-week shunt group [(21.9 +/- 2.1) and (10.2 +/- 1.4) micromol/g respectively, both P < 0.05]. The mPAP and expression levels of ICAM-1 and NF-kappaB p65 of the large, median, and small pulmonary artery endothelia cells of the 11-week shunt group were all higher than those of the 11-week control group (P < 0.05 or P < 0.01), whereas the expression levels of IkappaBalpha were all less obvious (P < 0.05 or P < 0.01). The plasma and lung tissue ICAM-1, IL-8, and MCP-1 levels of the 11-week shunt group were all significantly higher than those of the 11-week control group (all P < 0.01). The mPAP of the 11 week shunt + NaHS group was (23.2 +/- 3.0) mm Hg, significantly lower than that of the 11-week shunt group [(27.5 +/- 1.9) mm Hg, P < 0.05]. The ICAM-1 and NF-kappaB p65 expression levels of large, median, and small pulmonary artery endothelia cells of the 11-week shunt + NaHS group were all significantly weaker than those of the 11-week shunt group (P < 0.05 or P < 0.01), whereas the protein expression levels of IkappaBalpha in small and median pulmonary artery endothelia cells of the 11-week shunt + NaHS group were significantly higher than those of the 11-week shunt group (both P < 0.05). The plasma and lung tissue ICAM-1 contents of the 11-week shunt + NaHS group were (124 +/- 11) micromol/L and (19.9 +/- 2.5) micromol/g, both significantly lower than those of the 11-week shunt group [(154 +/- 20) micromol/L and (23.9 +/- 3.6) micromol/g respectively, both P < 0.01]. The plasma and lung tissue IL-8 contents of the 11-week shunt + NaHS group were (92 +/- 11) micromol/L and (15.0 +/- 1.7) micromol/g, both significantly lower than those of the 11-week shunt group [(121 +/- 17) micromol/L and (19.0 +/- 3.9) micromol/g respectively, both P < 0.01]. The lung tissue MCP-1 content of the 11-week shunt + NaHS group was (10.8 +/- 1.6) micromol/g, significantly lower than that of the 11-week shunt group [(13.5 +/- 1.4) micromol/g, P < 0.01].
  
  
  CONCLUSIONS
  H2S attenuates the development of pulmonary hypertension induced by high pulmonary blood flow through ameliorating pulmonary vascular inflammation. The inhibitory effect of H2S on the pulmonary vascular inflammation involves elevating IkappaBalpha expression, down-regulating NF-kappaB p65 expression and then inhibiting the expression of inflammatory related factors.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Key Lab of Molecular Cardiovascular Medicine, Ministry of Education, Beijing 100034, China.
authors.forename: Hong-fang
authors.initials: HF
authors.lastname: Jin
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Jia-min
authors.initials: JM
authors.lastname: Liang
authors.forename: Chao-shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Jun-bao
authors.initials: JB
authors.lastname: DU
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014657:Vasculitis / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016209:Interleukin-8; D013440:Sulfides; D051996:Transcription Factor RelA; D018799:Intercellular Adhesion Molecule-1; C025451:sodium bisulfide; D006862:Hydrogen Sulfide