Influence of endothelin-1 on nitric oxide and hydrogen sulfide pathways in vascular smooth muscle cells in rats / 中华实用儿科临床杂志

Objective To explore the effect of different concentrations of endothelin-1 (ET-1)on the en-dogenous nitric oxide (NO)and hydrogen sulfide (H2S)pathways of vascular smooth muscle cells (A7r5 cell lines)in rats.Methods A7r5 cell lines were divided into the control group and the experimental group.ET-1 at a concentra-tion of 10 -8-10 -6 mol/L was added into the experimental group,and as for the control group,the same volume of sterile phosphate buffered saline (PBS)buffer solution was added.The content of NO and H2S in A7r5 cell lines was detected by fluorescent NO probe and H2S probe after ET-1 stimulation for 48 h,respectively.The content of NO in the supernatant was measured by NO assay kit at 48 h of the incubation.The content of H2S in the supernatant was measured by polarographic H2S sensor at 48 h of the incubation. The expressions of inducible nitric oxide synthase (NOS2),endothelial nitric oxide synthase (NOS3),cystathionine -γ -lyase (CSE),cystathionine -β -synthase (CBS)and proliferating cell nuclear antigen (PCNA)were detected by the Western blot method.Results The rela-tive fluorescence intensity of the content of NO in the A7r5 cell lines of ET-1 10 -8,10 -7 and 10 -6mol/L groups (0. 078 ± 0. 080,0.075 ± 0.002,0.056 ± 0.009)was markedly lower than that in the control group(0.094 ± 0. 061), and the differences were statistically significant(F＝15.248,P＜0.05);Compared with the control group[(2. 131 ± 0. 484)μmol/L],the content of NO in the supernatant of the experimental groups [(1.391 ± 0.134 )μmol/L, (1.219 ± 0. 280)μmol/L,(1.116 ± 0.181)μmol/L]was significantly decreased,and the differences were statistically significant(F＝20.833,P＜0.01);NOS2 protein expression(0.457 ± 0.097,0.462 ± 0.116,0.438 ± 0.180)was decreased markedly compared with that of the control group(0.721 ± 0.222),and the differences were statistically sig-nificant(F＝6.196,P＜0.01),but the expression of NOS3 showed no significant differences(F＝2.669,P＞0.05). The relative fluorescence intensity of the content of H2S in the A7r5 cell lines of ET-1 10 -8,10 -7 and 10 -6mol/L groups (0.063 ± 0.002,0.056 ± 0.008,0.042 ± 0.009)was markedly lower than that in the control group (0.082 ± 0. 006),and the differences were statistically significant(F ＝16.297,P＜0.01);Compared with the control group [(29.439 ±4.236)μmol/L],the content of H2S in the supernatant of the experimental groups [(17.516 ±5.144) μmol/L,(14.481 ± 4.885)μmol/L]was significantly decreased,and the differences were statistically significant (F＝12.518,P ＜0.01).CBS protein expression(0.359 ± 0.096,0.270 ± 0.038,0.174 ± 0.051)was decreased markedly compared with that of the control group(0.707 ± 0.107),and the differences were statistically significant (F＝20.833,P＜0.01),and the expression of CSE showed no significant differences(F＝0.708,P＞0.05).The data showed that PCNA protein expression in the 10 -7mol/L ET-1 group(0.686 ± 0.180)significantly increased com-pared with that of the control group(0.437 ± 0.191),and the difference was statistically significant (t＝ -2.840,P＜0.01).Conclusion ET-1 stimulation can lead to the proliferation of vascular smooth muscle cells and down-regu-late its endogenous NO and H2S pathways.

Effect of endogenous sulfur dioxide on the apoptosis induced by cobalt chloride in the human pulmonary arterial endothelial cells / 中华实用儿科临床杂志

Objective To explore the effect of endogenous sulfur dioxide (SO2)on the apoptosis induced by cobalt chloride (CoCl2)in the human pulmonary arterial endothelial cells (HPAECs).Methods CoCl2was used in the primary HPAECs to mimize hypoxia-induced cell apoptosis.The aspartate aminotransferase 1(AAT1),and the key enzyme generating endogenous SO2 were over -expressed by transfecting HPAECs with lentivirus containing AAT1 cDNA.HPAECs were divided into 4 groups:vehicle group,vehicle + CoCl2 group,AAT1 group and AAT1 + CoCl2 group.The expressions of AAT1,B-cell lymphoma-2 (bcl-2),bcl-associated X protein (bax),Caspase-3 and activated Caspase-3 (cleaved Caspase-3)in the HPAECs were measured by Western blot.The AAT activity was assessed with colorimetry method.The SO2 content in the HPAECs was in situ observed by SO2-specific fluorescent probe.The HPAECs apoptosis was investigated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)assay.Results There were significant differences in the endogenous SO2 content,the expre-ssions of AAT1 and bcl-2,and the ratio of cleaved Caspase-3/Caspase-3 among 4 groups of HPAECs were (F＝147.364,23.738,6.521,64.884,all P＜0.05).However,there was no difference in the expression of bax among 4 groups of HPAECs (F＝1.620,P＞0.05).Compared with vehicle group,AAT activity [(0.96 ± 0.24)Carmen's unit/μg vs.(2.21 ± 0. 60)Carmen's unit/μg],endogenous SO2 content (40.71 ± 7.72 vs.105.60 ± 16.20)and bcl-2 expression (0.59 ± 0.19 vs.1.02 ± 0.20)in the HPAECs of vehicle +CoCl2 group were significantly de-creased,while the cell apoptosis assessed by TUNEL and the ratio of cleaved Caspase-3/Caspase-3 (1.56 ± 0.25 vs.0.95 ± 0.13)were significantly increased (all P＜0.05).However,there were no differences in the expression of AAT1 (0. 50 ± 0.12 vs.0.53 ± 0.11)in the HPAECs between vehicle group and vehicle+CoCl2 group (P＞0.05). The SO2 content (351.50 ± 42.43 vs.105.60 ± 16.20)and AAT1 expression (1.22 ± 0.33 vs.0.53 ± 0.11)in the HPAECs of AAT1 group were higher than those of vehicle group (all P ＜0. 05 ). Compared with AAT1 group, endogenous SO2content (333.50 ± 46.22 vs.351.50 ± 42.43)and the expression of AAT1 (1.26 ± 0.36 vs.1.22 ± 0.33)and bcl-2 (1.14 ± 0.38 vs.1.03 ± 0.27)in the HPAECs of AAT1 +CoCl2group did not change (all P＞0. 05).Moreover,no difference was observed in the HPAECs apoptosis assessed by TUNEL and the ratio of cleaved Caspase-3/Caspase-3 (0.51 ± 0.17 vs.0.50 ± 0.11)between the two AAT1 -overexpressed groups (all P ＞0. 05).Conclusion Endo-genous SO2inhibited the hypoxic HPAECs apoptosis stimulated by the treatment of CoCl2.

Effects of endogenous sulfur dioxide on the oxidative stress induced by cobalt chloride in the rat pulmonary artery smooth muscle cells / 中华实用儿科临床杂志

Objective To investigate the effects of endogenous sulfur dioxide (SO2) on the oxidative stress induced by cobalt chloride (CoCl2) in the rat pulmonary artery smooth muscle cells (PASMCs).Methods Rat PASMCs were treated with 200 μ mol/L CoCl2 to mimic the hypoxia insult.Endogenous SO2 generating enzyme aspartate aminotransferase 1 (AAT1) expression was upregulated or downregulated (AAT1 sh) by transfection with lentivirus.Rat PASMCs were randomly divided into 8 groups:vehicle group,vehicle + CoCl2 group,AAT1 group,AAT1 + CoCl2 group,scramble group,scramble + SO2 group,AAT1 sh group and AAT1 sh + SO2 group.SO2 donor Na2 SO3/NaHSO3 at concentration of 100 μ mol/L were added in scramble + SO2 group and AAT1sh + SO2 group.The expressions of AAT1,superoxide dismutase 1 (SOD1) and SOD2 in PASMCs were detected by Western blot method.In situ SO2 content in PASMCs was detected by fluorescent probe.The superoxide anions in PASMCs were labeled by dihydroethidium (DHE) probe under fluorescent microscope.Results Compared with the vehicle group,the levels of SO2 and the expressions of AAT1 (0.221 ± 0.002 vs.0.446 ± 0.004),SOD1 (0.076 ± 0.028 vs.0.171 ± 0.019) and SOD2 (0.080 ± 0.031 vs.0.196 ± 0.018) significantly decreased (all P ＜ 0.01),and superoxide anion increased in rat PASMCs of vehicle + CoCl2 group.Meanwhile,compared with vehicle + CoCl2 group,the levels of SO2 and the expressions of AAT1 (0.839 ± 0.056 vs.0.221 ± 0.002),SOD1 (0.177 ± 0.020 vs.0.076 ± 0.028) and SOD2 (0.195 ±0.018 vs.0.080-± 0.031) markedly increased (all P ＜ 0.01),and superoxide anion decreased in rat PASMCs of AAT1 + CoCl2 group.On the contrary,compared with the scramble group,the levels of SO2 and the expressions of AAT1 (0.062 ±0.017 vs.0.354 ±0.034),SOD1 (0.054 ±0.029 vs.0.157 ±0.023) and SOD2(0.180 ±0.100 vs.0.586 ± 0.176)significantly decreased (all P ＜ 0.01),and superoxide anion increased in rat PASMCs of AAT1sh group.Furthermore,compared with the AAT1 sh group,the levels of SO2 and the expressions of SOD1 (0.155 ± 0.022vs.0.054 ± 0.029) and SOD2 (0.578 ± 0.200 vs.0.180 ± 0.100) significantly increased (all P ＜ 0.01),and superoxide anion decreased in rats PASMCs of AAT1sh + SO2 group.Conclusion Endogenous SO2/AAT1 inhibits CoCl2-induced oxidative stress in rat PASMCs.

Evaluation of the changes in heart rate during head-up test predicting the efficacy of oral rehydration salts on postural tachycardia syndrome in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To predict the therapeutic efficacy of oral rehydration salts (ORS) by quantifying changes in heart rate during the head-up test (HUT) in children with postural tachycardia syndrome (POTS).</p><p><b>METHOD</b>Fifty-four children from Peking University First Hospital during July 2005 to September 2013 were enrolled into POTS group. Twenty healthy children were enrolled in this study as the control group. Children with POTS were treated with ORS and successfully followed up. HUT test was done before and at the end of the treatment. POTS children were further divided into responding group and the non-responding group depending on if the symptom scores were reduced by 50% or greater after the treatment. The heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes during the HUT test were analyzed between the control group and the POTS patients. A receiver operating characteristic (ROC) curve was used to analyze the predictive value of the increase in heart rates (from the supine to upright) and the maximum upright heart rate in 10 minutes after ORS treatment.</p><p><b>RESULT</b>POTS children were 6-17 (11.3 ± 3.0) years old and the control group children were 10-12 (11.0 ± 0.8) years old. The changes of the heart rate during the HUT was different between the POTS patients and the controls ((41 ± 10) vs. (20 ± 7) beats/min, t = -10.441, P = 0.000) . There was no significant difference between the two groups in the maximum upright heart rate in 10 minutes during the HUT ( (117 ± 12) vs. (114 ± 8) beats/min, t = -1.322, P = 0.192) . The symptom scores were reduced compared with those before treatment ((3.2 ± 1.8) vs. (5.7 ± 2.0), t = 10.958, P < 0.001) and the heart rate changes from supine to upright were decreased in 30 patients ((33 ± 11) vs. (41 ± 11) beats/min, t = 2.956, P = 0.006). Compared with the non-responding group (28 cases), the heart rate change during the HUT test was great in the responding group (26 cases) before treatment ((46 ± 10) vs. (37 ± 9) beats/min, t = -3.582, P = 0.001), and the maximum upright heart rate in 10 minutes was also high in the responding group ( (122 ± 12) vs. (113 ± 10) beats/min, t = -2.693, P = 0.010). The ROC curve showed that ORS for children with POTS would be predicted to be effective when the pre-treatment increase of heart rate was 41 beats/min (sensitivity 72% and specificity 70%), or when the maximum upright heart rate in 10 minutes was 123 beats/min before treatment (sensitivity 48% specificity 56%). When the two indices were used together, sensitivity was 84% and specificity was 56%.</p><p><b>CONCLUSION</b>The changes in heart rate during the HUT was useful in predicting the response to ORS in children with POTS.</p>

Changes of plasma intermedin during head-up tilt test in children with postural tachycardia syndrome and its significance / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore possible mechanisms of postural tachycardia syndrome (POTS) by comparing plasma intermedin (IMD) during head-up tilt test (HUTT) in children with POTS.</p><p><b>METHOD</b>The study subjects were divided into two groups: POTS group and control group. The POTS group consisted of twenty-nine children (male 14, female 15) with POTS, the mean age (12.4 ±3.1) years old, admitted into Peking University First Hospital from November 2013 to June 2014. The control group consisted of 32 healthy children (male 17, female 15). Their mean age was (11.6±2.2) years old, who were confirmed as healthy by physical examination and HUTT. Finapres Medical System was used to continuously monitor heart rate and blood pressure during HUTT, and electrocadiogram was performed. Supine systolic and diastolic blood pressure, mean arterial pressure (MAP), ΔMAP (standing mean arterial pressure-supine MAP), supine heart rate and ΔHR (standing HR-supine HR) were compared between POTS group and control group. Sandwich immunoluminescence assay was used to test plasma IMD. The plasma IMD level was compared in supine between POTS and control group. The plasma IMD level in supine was compared with HUTT in POTS group.</p><p><b>RESULT</b>No significant differences were found in age, height, weight, supine systolic and diastolic blood pressure, MAP, ΔMAP and supine heart rate between POTS group and control group (P>0.05). ΔHR in POTS group was significantly higher than that of control group ((48±10) vs. (22±7) beats /min, t=9.797, P<0.05). The plasma IMD level in POTS group was lower than that of control group in supine position ((497±61)×10(-6) vs. (529±58)×10(-6) mg/L, t=2.117, P<0.05). But, it was higher during HUTT than supine IMD in POTS group ((537±57) ×10(-6) vs. (497±61)×10(-6) mg/L, t=-2.464, P<0.05). The plasma delta IMD level (HUTT vs. supine) was positively correlated with delta HR in POTS group (r=0.435, P<0.05).</p><p><b>CONCLUSION</b>The excessively high heart rate during HUTT have a positive correlation with plasma IMD, which may play a role in the pathogenesis of POTS in children.</p>

Change of the renal hydrogen sulfide system in salt-sensitive hypertensive rats / 中华实用儿科临床杂志

Objective To study the change of the renal endogenous hydrogen sulfide (H2 S) pathway in the development of salt-sensitive hypertension in Dah1 rats.Methods Sixteen male Dah1 rats,in accordance with the random number table,were randomly divided into control group and high salt group fed with diet containing 80 g/kg NaCl.After 8 weeks,24 h urine sodium,24 h urinary protein,serum creatinine and serum urea were measured.The microstructural and ultrastructural changes in kidney were observed with light microscope and electronic microscope.The serum and kidney H2S contents were determined by using sulphur-sensitive electrode method.The mRNA levels of cystathionine β-synthase(CBS),cystathionine γ-lyase(CSE) and mercaptopyruvate sulfurtransferase(MPST) in renal tissue were determined by means of real-time polymerase chain reaction(RT-PCR).The protein expressions of CBS,CSE and MPST in renal tissue were detected by using Western blot.Results Compared with control group,high salt group rats had a significant rise in blood pressure,declined renal function,damaged renal structure,segmental glomerular sclero sis,small artery wall thickening,and occlusion of the lumen.Moreover,the endogenous H2S pathway in kidney of Dah1rats with high salt diet was downregulated markedly,demonstrated by the decreased serum and kidney H2S content,the reduced renal CBS,CSE and MPST mRNA expressions and CBS protein expression of kidney tissue.Conclusion The endogenous H2S/CBS pathway is downregulated during the development of salt-sensitive hypertension in Dah1 rats.

Changes of atrial natriuretic peptide and antidiuretic hormone in children with postural tachycardia syndrome and orthostatic hypertension: a case control study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The abnormal blood volume regulation is one of the most important pathogenesis in postural tachycardia syndrome in children. This study was designed to investigate the plasma atrial natriuretic peptide and antidiuretic hormone levels in postural tachycardia syndrome children, and their associations with the changes in heart rate and blood pressure in head-up test.</p><p><b>METHODS</b>Twenty-one postural tachycardia syndrome patients ((12 ± 2) years) and 26 healthy children ((12 ± 1) years) were included. According to blood pressure changes in head-up test, the postural tachycardia syndrome patients were divided into two subgroups: postural tachycardia syndrome with orthostatic hypertension and postural tachycardia syndrome without orthostatic hypertension. The plasma atrial natriuretic peptide and antidiuretic hormone levels were measured using enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The plasma atrial natriuretic peptide level in postural tachycardia syndrome patients was higher than the control (P = 0.004), whereas the difference in plasma antidiuretic hormone level between postural tachycardia syndrome and controls was not significant (P = 0.222). The plasma antidiuretic hormone level of patients suffering from postural tachycardia syndrome with orthostatic hypertension was much higher than that of children having postural tachycardia syndrome without orthostatic hypertension (P < 0.05). In postural tachycardia syndrome patients, the upright max heart rate was positively correlated with the plasma atrial natriuretic peptide level (r = 0.490, P < 0.05) and the upright systolic blood pressure was positively correlated with the plasma antidiuretic hormone levels (r = 0.472, P < 0.05).</p><p><b>CONCLUSIONS</b>There was a disturbance of plasma atrial natriuretic peptide and antidiuretic hormone in postural tachycardia syndrome children.</p>

Immune regulation of hydrogen sulfide in children with acute lymphoblastic leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lymphoblastic leukemia (ALL) and chemotherapy can cause immune imbalance, and gaseous molecule hydrogen sulfide (H2S) can participate in the process of immune response. This study aimed to investigate the immune regulation of H2S in pediatric ALL.</p><p><b>METHODS</b>Children (n = 78) with ALL admitted during 2010-2013 were included in this study. Two blood samples were collected in period of before chemotherapy, bone marrow remission and two days after chemotherapy, respectively. Serum contents of H2S and cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10) and macrophage inflammatory protein-1α (MIP-1α), were detected using ELISA method. Stepwise regression was used to analyze the correlation between H2S and cytokines. Furthermore, human Jurkat cells were cultured in vitro, and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells (PBMCs) were collected, contents of cystathionine γ-lyase (CSE) and certain cytokines were measured by Western blotting.</p><p><b>RESULTS</b>Serum concentrations of H2S, IL-1β, IL-6, IL-10 and MIP-1a in children with ALL were increased significantly (P < 0.01), while concentrations of IL-2, TNF-α, IFN-γ and IL-4 decreased obviously (P < 0.01). In patients after chemotherapy, concentrations of H2S and IL-10 were decreased significantly (P < 0.05), but IL-4 and IFN-γ concentrations increased markedly (P < 0.05). At remission stage, H2S, IL-1β, IL-4, IL-6, IL-10 and MIP-1α concentrations were further decreased markedly (P < 0.05), but concentrations of IL-2, TNF-α and IFN-γ increased again (P < 0.05). Protein contents of CSE, IL-10, IL-4 and IL-2 of PBMCs also increased markedly in children with ALL. Moreover, changes of CSE protein contents of PBMCs were consistent with serum H2S contents, and there were significant correlation between H2S and certain cytokines based on stepwise regression analysis. Furthermore, compared with those of PBMCs group, in vitro study indicated that Jurkat cells of H2S group expressed IFN-γ, IL-10, IL-4 and IL-2 protein increased obviously (P < 0.05), while IL-4, IL-2 and CSE expression of PPG group decreased markedly (P < 0.05).</p><p><b>CONCLUSION</b>Gaseous molecule H2S might participate in the process of immune regulation in pediatric ALL through modulating transcription and expression of cytokines.</p>

Effects of continuous intermedin infusion on blood pressure and hemodynamic function in spontaneously hypertensive rats / 老年心脏病学杂志（英文版）

Objective To examine the effects of exogenously administered intermedin (IMD,adrenomedullin-2) on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n =12),SHR group (n =12),IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour,n =12),and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour,n =12).Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax),left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2),aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor (CRLR);suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP).Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.

Serum hydrogen sulfide reduces in idiopathic pulmonary fibrosis patients / 基础医学与临床

Objective To explore the effect of endogenous H_2S in idiopathic pulmonary fibrosis(IPF) patients, and its relationship with the severity of IPF. Methods Plasma H_2S in 27 patients with IPF (IPF group) and 28 healthy people (control group) were tested. PaO_2, ESR, CRP, LDH, HRCT and pulmonary function in IPF group were tested to evaluate the severity of the disease at the same time. Then the concentrations of H_2S in aggravating and palliative period in IPF group were observed. Results (1) Compared with the control group, the concentration of plasma H_2S in IPF group was significantly reduced(P 0. 05). Conclusion Endogenous H_2S was probably involved in the course of IPF, and was associated with the progress of the disease.

Effect of Endurance Training on JAKs and SOCSs Expression of Left Ventricle Muscle in Rats / 中国运动医学杂志

Objective To evaluate Janus kinase (JAKs) and Suppressors of cytokine signaling(SOCSs) expression in myocardium after endurance training. Methods 30 male Sprague-Dawley rats undertook 10 weeks grade treadmill training program and were sacrificed at 0 and 24 h respectively after the last exercise. JAK1,JAK2,JAK3 and SOCS1 ,SOCS2,SOCS6 expression in the myocardium were determined by im munohistochemistry method. Results The percentage of JAK1 positive cell significantly increased immediately after last running and recovered to the sedentary level 24 hrs after exercise;The percentage of JAK2 positive cell significantly increased immediately after last running and continuously at a higher level 24 hrs after exercise (P0.05). The percentage of SOCS1 and SOCS2 positive cell also significantly increased both immediately and 24 hrs after exercise (P0.05). Conclusion Endurance training could induce different responses of JAK1,JAK2 and JAK3. The increased expressions of JAK1 and JAK2 might indicate the changes of JAK/STAT signal pathway in regulating myocardial function. The increased expressions of SOCS1 and SOCS2 after endurance training might indicate the increased exertion in regulating JAK/STAT signal pathway in cardiac muscle.

Role of Endogenous Hydrogen Sulfide in Airway Inflammation and Airway Responsiveness in a Rat Model of Chronic Passive-Smoking / 中国呼吸与危重监护杂志

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 intraporitoneally injected with normal saline, sodium hydrosulfide (NailS) or propargylglycine (PPG, an irreversible inhibitor of cystathionine-γ-lyase).The animals were divided into six subgroups,ie.Con group, Naris group, and PPG group, CS group, CS + Naris group, and CS + PPG group.After 4 months,lung histological change and airway tension were measured.The H2 S 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 < 0.05) ; the H2S levels of plasma were significantly higher in GS group,NariS group and CS + Naris group,and much lower in PPG group (P < 0.05, respectively).Compared with CS group, the H2 S levels of plasma were significantly higher in CS + Naris group, and much lower in CS + PPG group (P < 0.05, respectively).The H2S level of lung tissue in each group had no significant difference (P > 0.05).Compared with Con group, score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to Ach and KCI 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 + NariS group(P < 0.05), and vise versa in CS + PPG group (P < 0.01).Conclusion H2 S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airway inflammation and airway responsiveness.

Effect of midkine, a newly heparin - binding cytokine, on cardiovascular functions / 中国病理生理杂志

Midkine (MK) , a newly discovered heparin - binding growth factor, promotes growth, survival, and migration in various cells. Meanwhile, MK stimulates statistically significant forms in new arterioles and capillaries, causes vascular remodeling, prevents ischemia myocardial cells from injury via inhibiting apoptosis. MK also regulates the level of blood - fat.In general, MK plays key roles in cardiovascular diseases.

Effects of peptide fragments from the proadrenomedullin on cAMP——"The intramolecular regulation" of signal transduction pathway in cells / 中国药理学通报

Aim To study the effect of Peptide fragments that originate from the same proadrenomedullin on cAMP in rat aorta.Methods Isolated aortic tissues were exposed to ADM,PAMP and ADT for 2 h.The content of cAMP in the incubated media was assayed by radioimmunoassay.Results ① The content of cAMP in the aortic tissues that were exposed to ADM (10~(-7) and 10~(-8) mol·L~(-1)) was significantly increased. The content of cAMP in the aortic tissues stimulated by PAMP (10~(-8) mol·L~(-1))or ADT (10~(-8) mol·L~(-1))alone was significantly increased, compared with the control.② The content of cAMP was not in-creased when the tissues were treated with ADM (10~(-8) mol·L~(-1)) and PAMP (10~(-8) mol·L~(-1)) or ADT (10~(-8) mol·L~(-1)) in combination, compared with that after the treatment with ADM(10~(-8) mol·L~(-1))alone, but was significantly decreased than that in PAMP(10~(-8) mol·L~(-1)) or ADT(10~(-8)mol·L~(-1)) groups. After incubation with ADM,PAMP and ADT at the same dose (10~(-8) mol·L~(-1)), the content of cAMP did not change as compared with that of the ADM group (10~(-8) mol·L~(-1),P>0.05), but was greatly reduced, compared with that of the PAMP or ADT groups(10~(-8) mol·L~(-1),P<0.01).Conclusion ADM, PAMP and ADT which originate from the proadrenomedullin have an antagonism on cAMP production in rat aorta.

Urotensin Ⅱ aggravated β-glycerophosphate-stimulated calcification in cultured rat vascular smooth muscle cells / 中国药理学通报

Aim To investigate the effect of urotensin Ⅱ on vascular calcification.Methods Calcified VSMCs of rat in vitro were induced by β-glycerophosphate.Cellular calcium content,ALP activities,~(45)Ca accumulation and osteocalcin content were measured.Results Compared with those of control group,calcium content,ALP activities,~(45)Ca uptake and osteocalcin in calcified VSMCs increased greatly(P<0.01).Calcium content,ALP activities,~(45)Ca uptake and osteocalcin of calcified VSMCs stimulated by urotensin Ⅱ (10~(-10)、10~(-9) and 10~(-8) mol·L~(-1))were greatly increased in a concentration-dependent manner as compared with those of calcified group(P<0.01).Conclusion UrotensinⅡ aggravates the calcification of VSMCs induced by β-glycerophosphate.

Endoplasmic reticulum stress and cardiovascular diseases / 老年心脏病学杂志（英文版）

The endoplasmic reticulum (ER) serves several important functions, mainly post-translational modification, folding and assembly of newly synthesized secretary proteins, synthesizing lipids and cellular calcium storage. Various factors can disrupt ER homeostasis and disturb its functions, which leads to the accumulation of unfolded and misfolded proteins and to potential cellular dysfunction and pathological consequences, collectively termed ER stress. Recent progress suggests that ER stress plays a key role in the immune response, diabetes, tumor growth, and some neurodegenerative diseases. In particular, ER stress is involved in several processes of cardiovascular diseases, such as ischemia/reperfusion injury, cardiomyopathy, cardiac hypertrophy, heart failure, and atherosclerosis. Further research on the relation of ER stress to cardiovascular diseases will greatly enhance the understanding of these pathological processes and provide novel avenues to potential therapies.

Effects of different antithrombotic interventions on platelet activation in patients with atrial fibrillation / 国际脑血管病杂志

Objective To observe the effects of different antithrombotic interventions on the changes of plasma lysophosphatidic acid (LPA) level in patients with nonvalvular atrial fibrillation (NVAF) and to provide the basis for clinical antithrombotic therapy. Methods A total of 235 patients with NVAF who did not receive antithrombotic therapy diagnosed by clinical and auxiliary examinations were randomly allocated to receive aspirin (100 mg/d) plus dipyridamole (100 mg/d) (n =76), aspirin (100 mg/d) plus fixed-dose warfarin (1.25 mg/d) (n =79), and dose-adjusted warfarin (international normalized ratio (INR) range of 1.5 to 2. 1) (n =80). They gore redivided into <60, 60-75, and ≥76 year-old groups according to their age. The plasma LPA levels were measured and compared before treatment and 2 and 6 weeks after treatment. Results 1he plasma LPA levels were decreased more significantly in the aspirin plus fixed-dose group than those in the aspirin plus dipyridamole and dose-adjusted warfarin groups (all P < 0.01). Two and 6 weeks after treatment with aspirin plus dipyridamole in the < 60 year-old group, the plasma LPA levels were significantly lower than those before treatment (all P<0. 01). Two and6 weeks after treatment with aspirin plus fixed-dose warfarin in the < 60 year-old group, the plasma LPA levels were significantly lower than those before treatment (all P <0. 01). Two and 6 weeks after treatment with aspirin plus fixed-dose warfarin in the 60-75 year-old group, the plasma LPA levels were significantly lover than those before treatment (all P <0.01). Two and 6 weeks after the treatment with dose-adjusted warfarin (INR 1.5-2. 1) in patients in each age group, the plasma LPA levels were significantly lower than those before treatment. Conclusions 1he different antithromhotic therapeutic modalities have different effects on platelet activation in patients with NVAF in different age groups. The patients in the < 60 year-old group can receive aspirin plus dipyridamole, the patients in the < 75 year-old group can receive aspirin plus fix-dose warfarin, and the patients > 75 year-old, dose-adjusted warfarin (INR 1. 5-2. 1) should he recommend.

Relationship Between Lysophosphatidic Acid Levels in Cerebrospinal Fluid and Cerebral Vasospasm After Subarachnoid Hemorrhage / 国际脑血管病杂志

Objective: To observe the characteristics of dynamic changes of lysophosphatidic acid (LPA) levels in cerebrospinal fluid (CSF) in patients with subarachnoid hemorrhage (SAH) and its relationship with cerebral vasospasm (CVS) and to explore the pathogenesis of CVS. Methods: Sixty-seven patients with SAH diagnozed by clinical and accessory examinations were selected. The LPA levels in CSF were measured at 24 hours, day 7,14, and 28 respectively after the onset of symptoms,and they were compared with a control group. The correlation between LPA levels and CVS on the time course was also observed at the same time. Results: Of the 67 patients with SAH, a total of 29 patients (43.3%) occurred CVS, the average time of occurrence was 6. 6 days. There was no significant difference between the LPA levels in CSF in patients with SAH and the control group at 24 hours after the onset of symptoms; they were significantly higher than the control group at day 7 (P ＜0. 001); they were significantly higher than the control group at day 14 (P ＜ 0. 001), but they were significantly lower than those at day 7 (P ＜ 0. 01); they decreased to baseline at day 28, and there was significant difference compared with the control group. There was no significant difference between the LPA levels in the CVS group and those in the non-CVS group at 24 hours, they were significantly higher than those in the non-CVS group at day 7 (P ＜0. 001), they were still significantly higher than those in the non-CVS group at day 14 (P ＜0. 01); and there was no significant difference between the 2 groups at day 28. Conclusions: The LPA levels in CSF in patients with SAH increased significantly from day 7 to day 14 after the onset of symptoms, and they had obvious association with CVS on the time course. The detection of the LPA levels in CSF may have important significance in predicting the occurrence of CVS.

Elevated plasma lysophosphatidic acid levels and risk of silent brain infarction in patients with atrial fibrillation / 中华神经科杂志

Objective To investigate the changes of plasma lysephosphatidic acid (LPA) or acidic phospholipids (AP) levels in patients with nonvalvular atrial fibrillation(NVAF) or NVAF associated with silent brain infarction (SBI) and to provide biochemistry evidence to antithrombotic therapy. Methods Plasma LPA/AP levels was examined in blood freshly sampled in 235 cases of NVAF who were not receiving any antithrombotic therapy, 116 cases SBI who were not with NVAF and 120 cases healthy volunteers as control enrolled in the LPA and stroke prevention study. Plasma LPA was assayed by measuring its inorganic phosphorus after separation by chromatograph. Meanwhile, the platelet activation in NVAF or (and) SBI were observed. Results SBI was found in 31.5% of the participants with NVAF, and in 37.6% of the elderly NVAF subjects (age60 years old). LPA/AP levels were significantly increased in NVAF with SBI group((3.78±0.61) μmol/L) compared with controls ((2.66±0.49) μmol/L, 95% CI 3.47-4.21,P = 0.000), NVAF without SBI group ((3.29±0.57) μmol/L, 95 % CI 3.01-3.76, P = 0.008), SBI without NVAF group((3.17±0.54) μmol/L, P=0.004). The platelet activation was significantly higherin NVAF with SBI group, the odds ratio (95% CI) was 21.39(10.17 to 45.02),than those in NVAF without SBI group (P<0.01). Conclusion The plasma LPA/AP levels were significantly elevated in NVAF or NVAF with SBI, NVAF contributes to the risk of SBI. Platelet activation may play an important role in the pathogenesis of thromboembolism in NVAF and the measurement of LPA reflects activation of platelets in vivo and may be a useful marker for the diagnosis of thrombosis or prothrombotic states.Consideration of the role of antiplatelet therapy should be given when choosing antithrombotic therapy to NVAF-associated ischemic stroke.

Hydrogen sulfide system in the pathogenesis of renovascular hypertension in rats / 老年心脏病学杂志（英文版）

Objective To investigate the role of hydrogen sulfide (H2S) synthases/H2S pathway in the pathogenesis of renovascular hypertension.Methods Wistar rats were subdivided into 4 groups:(1) 2-kidney,1-clip (2K-1C group,n=7),(2) control (n=7),(3)sham (n=7),and (4) 2K-1C plus sodium hydrosulfide (NariS) (NariS-treated group,n=7).The systolic blood pressure (SBP) was measured by a tail-cuff method using a pulse transducer once a week.Four weeks later,all rats were killed and the concentration of plasma hydrogen sulfide (H2S),the activity of the H2S syntha.ses in the kidneys on both sides,the plasma angiotensin Ⅱ concentration,and the left-to-whole heart weight ratio were measured.Results The SBP was significantly increased in the 2K-IC group (185.4± 14.0mmHg) comparing with those in the sham group (112.9±6.5mmHg,,or the NariS-treated group(134.8±9.5mmHg) (both P＜0.01).At 4 weeks,the angiotensin Ⅱ concentration in the plasma was increased in the 2K-1C and NariS-treated group,comparing with the control and the sham group (306.92±7.03 pg/ml and 240.73±13.22 pg/ml vs 122.6±25.49 pg/ml and 125.95±10.55 pg/ml,respectively,both P＜0.05).The plasma H2S concentration and the activity of H2S synthases in the left kidney were decreased in the 2K-1C group comparing with those in the sham and the control groups.There was no difference of the activity of the H2S synthases in the right kidneys among the 4 groups.The left-to-whole heart weight ratio was increased in the 2K-1C and the NariS-treated group camparing with that in the sham and natural control groups.Conclusions Dysfunction of the H2S synthases/H2S pathway was involved in the 2K-1C-induced renovascular hypertension in rat.Exogenous administration of H2S donor can attenuate the development of hypertension.These findings suggest that the H2S synthases/H2S pathway participates in the pathogenesis of renovascular hypertension.