0.05) in vitamin D_3 plus nicotine (VDN) group. The values of +LV dp/dt_ max and-LV dp/dt_ max were significantly lower in VDN group (P

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.

Objective To test the hypothesis that IL-10 may promoting left ventricular remodeling and cardiac function by modulating extracellular matrix after acute myocardial infarction. Methods Male adult rats were randomly divided into three groups:control group (n=6),MI/AAV2 group (n=16) and MI/AAV2-IL-10 group (n=16). Establishing animal modol of experimental myocardial infarction and recombinant adeno-associated virus type 2 (AAV)/IL-10 (AAV2-rhIL-10) and AAV2 were injected around the ischemic zone. Echocardiography parameters,hemodynamic parameters,left ventricular mass index (LVMI),collagen volume fraction (CVF),perivascular circumferential area (PVCA),collagen type Ⅰ&Ⅲ volume fraction and mRNA levels of collagen type Ⅰ&Ⅲ,matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were compared among the three groups. Results Improved cardiac function was observed in MI/AAV2-IL-10 group shown by echocardiography and hemodynamic examination. Four weeks after myocardial infarction,thickness of different parts of LV was not different in MI/AAV2-IL-10 group and MI/AAV2 group. Nevertheless CVF,PVCA and collagen type Ⅰ volume fraction was significantly descending in remote zone of MI/AAV2-IL-10 group compared with that of MI/AAV2 group. The mRNA expression of collagen type I and MMP-2 was lower in MI/AAV2-IL-10 group than that in MI/AAV2 group. Conclusion Recombinant IL-10 expression mediated by AAV2-rhIL-10 transfection of rats' myocardium promotes LV remodeling and cardiac function after acute myocardial infarction. The promotion was partially achieved by inhibition myocardium collagen deposition.

Objective To test the hypothesis that IL-10 may promoting left ventricular remodeling and cardiac function by modulating extracellular matrix after acute myocardial infarction. Methods Male adult rats were randomly divided into three groups: control group (n=6) , MI/AAV2 group (n=16) and MI/AAV2-IL-10 group (n=16). Establishing animal modol of experimental myocardial infarction and recombinant adeno-associated virus type 2 (AAV)/IL-10 (AAV2-rhIL-10) and AAV2 were injected around the ischemic zone. Echocardiography parameters, hemodynamic parameters, left ventricular mass index (LVMI) , collagen volume fraction (CVF) , perivascu-lar circumferential area (PVCA) , collagen type Ⅰ & Ⅲ volume fraction and mRNA levels of collagen type Ⅰ & Ⅲ , matrix metalloproteinases-2 ( MMP-2 ) and tissue inhibitor of metalloproteinase-1 ( TIMP-1) were compared among the three groups. Results Improved cardiac function was observed in MI/AAV2-IL-10 group shown by echocardiography and hemodynamic examination. Four weeks after myocardial infarction, thickness of different parts of LV was not different in MI/AAV2-IL-10 group and MI/AAV2 group. Nevertheless CVF, PVCA and collagen type Ⅰ volume fraction was significantly descending in remote zone of MI/AAV2-IL-10 group compared with that of MI/ AAV2 group. The mRNA expression of collagen type I and MMP-2 was lower in MI/AAV2-IL-10 group than that in MI/AAV2 group. Conclusion Recombinant IL-10 expression mediated by AAV2-rhIL-10 transfection of rats' myocardium promotes LV remodeling and cardiac function after acute myocardial infarction. The promotion was partially achieved by inhibition myocardium collagen deposition.

Aim To observe the influence of hydrogen sulfide on L-arginine/nitric oxide synthase(NOS)/NO pathway,explore the interaction between H_2S and NO as cardiovascular regulatory gasotransmitters.Methods Aortic thin slices in vitro were administrated with NaHS(10~(-7) mol?L~(-1)～10~(-4) mol?L~(-1)),a donor of H_2S,and incubated for 4 hours,or 50 ?mol?L~(-1) NaHS and incubated for 2 h,4 h and 6 h,respectively.The nitrite production Was measured with greiss assay;NOS activity and L-arginine transportation,with isotope tracer method;the eNOS and CAT1-A gene expression,with RT-PCR.Results After being given with NaHS(50 ?mol?L~(-1)) one time,and incubating for 2 h,the nitrite production decreased by 62%,NOS activity reduced by 48% and L-arginine transport decreased by 50%.After incubation for 6 h,the nitrite production further was inhibited by 19%(P0.05).NaHS(10~(-7) mol?L~(-1)～10~(-4) mol?L~(-1)) inhibited the L-arginine/NOS/NO pathway in a dose-dependent manner,and IC_(50) was 0.499,3.198 and 3.927 ?mol?L~(-1)(P

Objective:To investigate the changes of pulmonary IMD and its receptor system - calcitonin receptor-like receptor (CL) and receptor activity modifying proteins (RAMPs) mRNA in acute lung injury(ALI) induced by oleic acid of rats. Methods: Contents of IMD in plasma and lung homogenates were measured by radioimmunoassay(RIA). The lung mRNA of IMD, CL and RAMPs was determined by semi-quantitative RT-PCR. Results: Compared with control group, in ALI group, the contents of IMD_ 1-53 in plasma and lung homogenates were decreased by 20.8% and 74.5% (all P

Aim To determine the protective effects of IMD on ischemia/reperfusion(I/R) injury and its possible mechanism.Method Isolated rat hearts were perfused by Langendorff mode,and after 45 min global ischemia and 30 min reperfusion ventricular function was measured on a Power Lab,and adequate amount of ventricular tissues and perfusate were collected for biochemical measurement.Results Treatment with IMD during the reperfusion period significantly attenuated the effects of I/R on cardiac function inhibition and tissue injury.Compared with I/R group,IMD induced increase in △LVP,LV(dp/dtmax,HR and CF,whereas induced decrease in LVDP.Reperfusion with IMD exerted decrease in LDH,total protein,Mb and MDA content compared with I/R group,but increased myocardial cAMP content.All these values were similar to the effects of ADM.Furthermore,I/R induced significant increase in Bmax and Kd value.Conclusion IMD exerted beneficial effects on cardiac injury induced by I/R which might be mediated by cAMP pathway.And the cardioprotective effects of IMD were equal to ADM,a potent cytoprotective factor.

AIM　To investigate effect of urotensin Ⅱ (UⅡ)on proliferation of aort a smooth muscle cells （ASMC）of rat and study the signal transduction pathway o f it. METHODS　In cultured ASMC of rat, UⅡ was used to stimulate proliferation of these cells and levels of ［3H］-TdR incorporation were used to evaluate the speed of DNA synthesis, and different inhibitors were used to s tudy the action of different signal transduction pathway of mitogenic effect of UⅡ on VSMC. RESULTS　1×10-9～1×10-7 mol*L- 1 UⅡ caused marked concentration-dependent increasing of ［3H］-TdR i ncor poration of ASMC. ［3H］-TdR incorporation of 1×10-9,1×10-8 and 1×10-7 mol*L-1 UⅡ were 22%（P<0.05）, 57%（P<0.01）and 65%（P<0.01）higher than control. Nicardipine, H7, W7 and PD98059 , which are inhibitors of calcium channel, PKC, CaM-PK and MAPK respectively, inhibited the effects of UⅡ obviously, with the inhibitory rate by 55%（P< 0.01）, 27%（P<0.01）,18%（P<0.05）and 16%（P<0.05）respectively . CONCLUSION　UⅡ is a strong mitogen for VSMC and the mitogenic e ffect of UⅡ is probably mediated by Ca2+, PKC, CaM-PK and MAPK signal tr ansduction pathway.

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.

] AIM: Lysophosphatidic acid (LPA) is a bioactive phospholipid known to have growth factor-like activity on fibroblasts, and is involved in cardiovascular diseases. Besides direct effects, usually, LPA can work together with other bioactive factors to regulate cardiovascular homeostasis by induction of their expression and production, or increase in their activity. Among variety of bioactive factors, adrenomedullin (ADM) is a multifunctional peptide with an important cytoprotective effect against cardiovascular damage, but the interaction between ADM and LPA on adventitia remains unknown. METHODS: The experiment was performed on the bath of isolated rat aortic adventitia, ADM produced and secreted from adventitia stimulated by LPA was detected by using radioimmunoassay, proliferation in adventitia cells was evaluated by the level of [3H]-thymine incorporation, and prepro ADM gene expression was measured by semi-quantitative reverse transcriptase polymerase chain reaction. RESULTS: It was found that LPA stimulated aortic adventitia to secrete ADM and express its mRNA in a concentration-dependent manner. ADM inhibited LPA-induced proliferation in adventitial cells, and attenuated the activity of mitogen activated protein kinase (MAPK) stimulated by LPA. In contrast, the treatment with specific antagonists of ADM receptor potentiated the LPA-induced proliferation in adventitial cells. CONCLUSION: LPA stimulates adventitia to produce and secrete ADM, and in turn, ADM produced by adventitia regulates the vascular biological effects of LPA. [