Objective To investigate the role of endogenous Hydrogen Sulfide ( H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking. Methods Male SD rats were randomly divided into a control group ( breathing fresh air) and a passive smoking group [ cigarette smoking( CS) passively] , with 18 rats in each group. Six rats in each group were randomly intraperitoneally injected with normal saline, sodium hydrosulfide ( NaHS) or propargylglycine ( PPG, an irreversible inhibitor of cystathionine- γ-lyase) . The animals were divided into six subgroups, ie. Con group, NaHS group, and PPG group, CS group, CS+ NaHS group, and CS + PPG group. After 4 months, lung histological change and airway tension were measured. The H2S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay. The expression of cystathionine-γ-lyase ( CSE) was measured by western blot. Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group( P lt;0. 05) ; the H2 S levels of plasma were significantly higher in CS group, NaHS group and CS + NaHS group, and much lower in PPG group ( P lt; 0. 05, respectively) . Compared with CS group, the H2S levels of plasma were significantly higher in CS + NaHS group, and much lower in CS + PPG group( P lt; 0. 05, respectively) . The H2S level of lung tissue in each group had no significant difference ( P gt; 0. 05) . Compared with Con group,score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to ACh and KCl was significant augmented in CS group. Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS +NaHS group( P lt;0. 05) , and vise versa in CS + PPG group( P lt; 0. 01) . Conclusion H2S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airwayinflammation and airway responsiveness.
目的 研究同型半胱氨酸转硫途径、维生素B6及内源性硫化氢在慢性阻塞性肺疾病急性加重期（AECOPD）中的作用。 方法 2010年2月－4月间筛选AECOPD患者16例和健康志愿者（对照组）13例，测定AECOPD患者加重期、缓解期及对照组的肺功能、血清硫化氢（H2S）、丙二醛（MDA）、叶酸、维生素B12、C反应蛋白、白介素6、血浆同型半胱氨酸、胱硫醚、半胱氨酸和维生素B6的浓度。计算半胱氨酸转化率（半胱氨酸浓度/胱硫醚浓度）与胱硫醚转化率（胱硫醚浓度/同型半胱氨酸浓度）参与分析。 结果 ① 加重期血清MDA水平[（7.3 ± 5.1）nmol/L ]比缓解期[（3.0 ± 1.4）nmol/L ]和对照组[（3.0 ± 2.2）nmol/L ]均升高（P＜0.01）；血清MDA水平与第1秒用力呼气容积/用力肺活量（FEV1/FVC）、第1秒用力呼气容积占预计值百分比（FEV1%预计值）呈负相关。② 加重期血清H2S水平与血浆维生素B6水平较缓解期与对照组降低（P＜0.01）；缓解期血清H2S水平[（47.2 ±5.1） μmol/L ]高于对照组[（38.8 ± 2.1） μmol/L ]，P＜0.01；血清H2S水平、血浆维生素B6水平均与FEV1%预计值呈正相关（r=0.651、0.680，P＜0.01），均与血清MDA水平呈负相关（r=-0.334、-0.448，P＜0.05）。③ 加重期半胱氨酸转化率（3.97 ± 2.41）低于缓解期（5.92 ± 2.18）与对照组（6.14 ± 3.15）差异有统计学意义（P＜0.05）；而胱硫醚转化率则相反。④ 叶酸与维生素B12水平各组间均无差异。 结论 提高AECOPD患者维生素B6及H2S浓度可能能促使AECOPD患者向稳定状态转归，减轻氧化应激损伤。维生素B6与H2S可能成为AECOPD患者的一个新的治疗点。Objective To study the roles of homocysteine (Hcy) transsulfuration pathway, Vitamin B6 and endogenous hydrogen sulfide in treating patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Sixteen AECOPD patients and 13 healthy controls (Control group) from February to April 2010 were recruited in this study. Lung function, serum hydrogen sulfide (H2S), malondialdehyde (MDA), folate, vitamin B12, C-reactive protein (CRP), interleukin-6 (IL-6), Hcy, cystathionine, cystein (Cys) and vitamin B6 were all measured for all the patients in the acute exacerbation period and alleviation period and healthy controls. The conversion rate of Cys (expressed as Cys/cystathionine) and the conversion rate of cystathionine (expressed as cystathionine/Hcy) were calculated for analysis. Results Serum MDA level for patients in the acute exacerbation period (AE period) [(7.3 ± 5.1) nmol/L] was significantly higher than that in the alleviation period [(3.0 ± 1.4) nmol/L] and in the healthy controls [(3.0 ± 2.2) nmol/L] (P ＜ 0.01). Serum MDA level was negatively correlated with percentage of FEV1 in predicted FEV1 (FEV1% pred) and FEV1/FVC. Serum H2S level and plasma vitamin B6 level for patients in the AE period were significantly lower than those in the alleviation period and in the healthy controls (P ＜ 0.01), and serum H2S level was significantly higher in the alleviation period [(47.2 ± 5.1) μmol/L] than in the controls [(38.8 ± 2.1) μmol/L] (P ＜ 0.01). Both serum H2S and plasma vitamin B6 levels were correlated positively with FEV1% pred for patients in the AE period and healthy controls (r=0.651, 0.680; P ＜ 0.01), but negatively correlated with serum MDA level (r=-0.334, -0.448; P ＜ 0.05). The conversion rate of Cys for patients in the AE period (3.97 ± 2.41) was significantly lower than that in the alleviation period (5.92 ± 2.18) and the control group (6.14 ± 3.15) (P ＜ 0.05), but the conversion rate of cystathionine was just the opposite (P ＜ 0.05). There were no significant differences in the levels of serum folate and vitamin B12 among the three groups. Conclusion Raising the Vitamin B6 and H2S level may facilitate stabilizing of conditions in patients with AECOPD and reduce oxidative stress. Therefore, it may become a new treatment method for AECOPD.
Objective To explore the influences of hydrogen sulfide （H2S） on acute necrotizing pancreatitis （ANP）. Methods Forty-three SD male rats were grouped by random number table， and divided into five groups：the sham group （n=4）， ANP group 〔n=21， which was divided into 3 subgroups：3， 6， and 12 hours group （n=7）〕， NaCl＋ANP group （n=4）， NaHS＋ANP group （n=7）， and PAG＋ANP group （n=7）. Models of ANP were formed byretrograde cholangiopancreatography injection of 5% sodium taurocholate. The NaCl＋ANP group， NaHS＋ANP group， and PAG＋ANP group rats were given pretreatment of saline， NaHS， or PAG at 1 hour before modelingrespectively. The levels of serum amylase （AMY）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， blood urea nitrogen （BUN）， and creatinine （Cr） were detected， and the pathological histological changes of pancreatic tissues were observed. Results The levels of serum AMY， AST， ALT， BUN， and Cr were increased in ANP group. The levels of serum AMY， AST， ALT， BUN， and Cr in the NaHS＋ANP group were higher than those of NaCl＋ANP group （P＜0.05）， and the pathological damage of the pancreatic tissues was more serious in the NaHS＋ANP group. The levels of serum AMY， AST， ALT， BUN， and Cr in the PAG＋ANP group were lower than those of NaCl＋ANPgroup （P＜0.05）， and the pathological damage of pancreatic tissues in the PAG＋ANP group was not so serious as in the NaCl＋ANP group. Conclusions The impairment of liver， kidney， and pancreas function in ANP rats may be related to elevated H2S concentration. Prophylactic administration the PAG of H2S antagonist can improve the function of the liver， kidney， and pancreas， and have the effects of organ protection.
Objective To study the role of hydrogen sulfide （H2S） in prophase of acute peritoneal cavity infection. Methods NaHS was taken as a donor of H2S. Seventy-two Sprague-Dawley rats were divided into 4 groups randomly：control group， cecal ligation and puncture （CLP） and treated with natural saline group，CLP and treated with NAHS group， and CLP and treated with DL-propargylglycine （PAG， an inhibitor of H2S formation） group. Selected 6 rats at 2h， 6h， and 12h after treatment in each group. The contents of TNF-αand H2S in serum and the content of MPO in intestinal tissue were measured， respectively. The histopathological change of ileum tissues were observed at 6 h after treatment in each group. Results The H2S could alleviate CLP-induced inflammation obviously， decrease the content of TNF-α in serum when inflammation，and attenuate the infiltration of neutrophilic granulocyte in small intestine. Conclusion The H2S has anti-inflammation effect in prophase of acute peritoneal cavity infection.
ObjectiveTo investigate the potential role and mechanism of hydrogen sulfide (H2S) in regulating arterial baroreflex (ABR) in septic rats. MethodsThe rat model of cecal ligation and puncture (CLP) induced sepsis was established. Fortyseven male SpargueDawley rats were randomly divided into 9 groups: ① Sham operation (SO)+0.9% NaCl (NS) intravenous injection (i.v.) group; ② SO+NaHS i.v. group; ③ CLP+NaHS i.v. group; ④ SO+artificial cerebrospinal fluid (aCSF) bilater nucleus tractus solitarii (NTS) microinjection group; ⑤ SO+NaHS bilater NTS microinjection group; ⑥ SO+vehicle (DMSO)+NaHS group; ⑦ SO+Gli+NaHS group; ⑧ CLP+vehicle (DMSO) group; ⑨ CLP+Gli group. The ABR function was measured before administration and 5 min and 30 min after administration. Results① The ABR value of rats at different time in the same group: Compared with the ABR value before administration in the SO+NaHS i.v. group, CLP+NaHS i.v. group, SO+NaHS bilater NTS microinjection group, and SO+vehicle+NaHS group, the ABR values of rats significantly decreased at 5 min and 30 min after administration (Plt;0.05, Plt;0.01), which significantly increased in the CLP+Gli group at 5 min and 30 min after administration (Plt;0.05). ② The ABR value of rats at the same time in the different groups: Before administration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v.group (Plt;0.05). At 5 min and 30 min after adminis tration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v. group (Plt;0.05), which in the SO+NaHS i.v. group or SO+NaHS bilater NTS microinjection group was significantly lower than that in the SO+NS i.v. group or SO+aCSF bilater NTS microinjection group, respectively (Plt;0.05, Plt;0.01), in the SO+Gli+NaHS group or CLP+Gli group was significantly higher than that in the SO+vehicle+NaHS group or CLP+vehicle group, respectively (Plt;0.05). ConclusionsH2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the downregulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.
Objective To investigate the relation between gaseous signal molecule hydrogen sulfide (H2S) and diseases. Methods Literatures about the advancement of H2S were reviewed and analyzed. Results H2S is recognized as a novel gaseous signal molecule. By acting specially on ＫATPchannels, H2S can relax smooth muscle cells to regulate blood pressure.It even plays an important roles in pulmonary hypertension, ischemia/reperfusion injury, neurotransmission， apoptosis and inflammatory reaction. Conclusion H2S has been regarded as the third gaseous signal molecule， which exerts many physiological and pathological effects on mammals, and will pave way for development of new drugs and provide therapeutic intervention for various diseases.
ObjectiveTo summarize the mechanism of hydrogen sulfide (H2S) in regulating autophagy and ameliorating multi-organ dysfunction in the treatment of sepsis.MethodThe relevant literatures at home and abroad in recent years were systematically searched and read to review the mechanism of H2S in regulating autophagy and ameliorating multi-organ dysfunction during sepsis.ResultsAs a new medical gas signal molecule, H2S could regulate autophagy by regulating multiple signal pathways such as Nrf2, NF-κB, MAPK, AMPK, etc., then ameliorated multi-organ dysfunction in sepsis.ConclusionH2S inhibits inflammation, oxidative stress, and apoptosis by regulating autophagy, thus ameliorating multi-organ dysfunction in sepsis, which is expected to become an effective therapeutic target for sepsis.