Endothelial nitric oxide synthase traffic inducer in the umbilical vessels of the patients with pre-eclampsia

The expression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） was examined in the umbilical vessels of the patients with pre-eclampsia （PE） to explore its possible role in the pathogenesis of PE. The NOSTR1N rnRNA in umbilical tissues was determined by RT-PCR. The eNOS activity in umbilical vessels was spectrophotometrically detected. NO2 /NO3, the stable metabolic end products of NO, was measured by using nitrate reductase. RT-PCR showed that the expression level of NOSTRIN was significantly higher in women with PE than in the normal group （P〈0.01）. The activity of eNOS was significantly decreased in PE group [（12.83±3.61） U/mg] than in normal group [（21.72±3.83） U/mg] （P〈0.01）. The level of NO2-/NO3- in PE patients （27.53±7.48） pmol/mg was significantly lower than that of normal group （54.27±9.53） μmol/mg （P〈0.01）. The significant negative correlation existed between the expression of NOSTRIN and the activity of eNOS in umbilical vessels of women with PE （r=-0.58, P〈0.01）. It was concluded that the level of NOSTR1N expression was increased in umbilical vessel of women with PE, indicating that it may be involved in the pathogenesis of PE.     

Placental Isoferritin Action in Pathogenesis of Pre-eclampsia and/or Intrauterine Growth Retardation and Its Earlier Predictive Value

Pre- eclampsia and intrauterine growth retarda-tion(IUGR) are major sources of clinical morbidityand mortality in pregnant women and prenatal in-fants.Their mechanisms are not completely clear.The imbalance of maternal- fetal immune interactionwas demonstrated to play a role in them[1] .Recentlyplacental isoferritin (PLF) was demonstrated to be asignificant immune regular factor in pregnant im-mune inhibition[2 ] ,butitsrole in pathogenesisof pre-eclampsia and/or IUGR is unknown.In this s…     

The role of neutrophil activation in pathogenesis of preeclampsia

Pre- eclampsia,a common pregnancy complica-tion,isone of the leading causesof maternal mortali-ty and perinatal mortality and modality.The patho-genesis of this disease remains unclear.Endothelialdamage,which appears to be common to the patho-physiologicalfeatures of pre- eclampsia,has been doc-umented[1] .However,neutrophil activation may playan importantrole in vascular endothelium damage[2 ] .In this study,the CD1 1 b expression was examinedby using flow cytometry,and the levelsof plasma e…     

Expression of Platelet Membrane Glycoprotein Ib/Ⅸ/Ⅴ Complex,a Receptor of Thrombin,in Patients with Hemorrhagic Thrombopathy

To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.     

The Expression of PLF in Placenta in Pregnancy-Induced Hypertension and the Relationship between the PLF and Serum VCAM-1

Summary:To study the expression of placental isoferritin(PLF)in placental tissue of pregnancy-in-duced hypertension(PIH)and the relationship between the level of expression of PLF and theamount of vascular cell adhesion molecule-1(VCAM-1)in serum,immunohistochemical techniquewas used to detect the expression of PLF in placenta tissue in 45 PIH patients(PIH group)and 15normal pregnant women(normal group).High resolution pathological image analysis system(HPIAS-100)was employed to determine the quantity of PLF.The VCAM-1 in serum was exam-ined by enzyme linked immunoabsorbent assay(ELISA).The results showed that the levels of PLFexpressions in moderate and severe PIH patients were significantly lower than that of normal group(P<0.01).The serum VCAM-1 was significantly decreased in PIH group(1310±177ρ/mg/ml)than that of normal group(609±72ρ/ng/ml,P<0.01).The significant negative correlation exist-ed betweene the expression of PLF in placental tissue and the serum VACM-1(r=0.58,P<0.01).It was concluded     

Influence of L-arginine on the Expression of eNOS and COX2 in Experimental Pulmonary Thromboembolism

The influence of L-arginine on endothelial nitric oxide synthase (eNOS) and cyclooxy-genase 2 (COX2) was observed in experimental pulmonary thromboembolism and the action mechanism on pulmonary thromboembolism was explored. Wistar rats were randomly divided into control group, model group and treatment group. Pulmonary thromboembolism models were established by auto-blood back transfusion, and L-Arg 100 mg/kg was intraperitoneally injected after successful model preparation. The animals were sacrificed at 3 h, 1 day, 3 days and 7 days after embolism. Plasma NO, TXB2 and 6-Keto-PGF1αwere detected. The expression of eNOS and COX2 protein and mRNA in pulmonary tissues was detected by immunohistochemistry and RT-PCR respectively. The results showed that pulmonary thrombosis could be seen post pulmonary embolism and inflammatory reaction was significant. Plasma NO was decreased (P<0.01), and the levels of TXB2, 6-Keto-PGF1αand T/P ratio were all elevated. The expression of eNOS protein and mRNA in the pulmonary tissue was down-regulated (P<0.05), while that of COX2 protein and mRNA was upregu-lated (P<0.01). In treatment group, the level of NO was increased, the levels of TXB2 and T/P ratio were decreased, but the level of 6-Keto-PGF1αwas increased. The expression of eNOS protein and mRNA in pulmonary tissue was upregulated (P<0.05), while that of COX2 protein and mRNA was down-regulated (P<0.05). In conclusion, L-arginine can educe the role of pulmonary tissue protection through up-regulating the expression of intra-pulmonary NOS and down -regulating COX2 in pulmonary thromboembolism.     

Study on the Correlation of Plasma NO, ET-1 and ALT in the Patients with Chronic Hepatitis and Cirrhosis

Nitric oxide ( NO) is a small molecular sub-stance with many biological functions.NO is an un-stable molecule with free radical( or group) struc-ture. Its half life in vivo is 1 to 5s and is reduced tothe stable terminal products( NO2 -/NO3 -) quickly.Atpresent,many researchers reported that the levelof NO is related with the degree of liver disease. Wedetermined the levels of NO,endothelin- 1 ( ET- 1 )and ALT in the in- patients with chronic hepatitis Band active cirrhosisand analyze t…     

The relationship between constitutive nitric oxide synthase (cNOS) and pregnancy induced hypertension

Summary To study the relationship between constitutive nitric oxide synthase (cNOS) and pregnancy induced hypertension (PIH), cNOS expression and localization in placental villi of PIH patients (n=15) and normal pregnancy patients (n=15) were immunohistochemically studied. The positive immunostaining of cNOS was located in trophocytes and cytoplasm of vascular endothelial cells. The positive rate in PIH patients was much higher than that in cases of normal pregnancy. The positive rates were 34. 40 % in mild, 44. 74 % in middle and 50. 14% in severe PIH patients respectively. There was a significant difference in positive rate among the mild, middle and severe PIH patients (P<0.01). It is concluded that the increase of cNOS activity probably was the results of protective or compensatory mechanism of PIH course.     

妊高征患者胎盘中一氧化氮合酶含量的变化及其意义

为探讨胎盘中一氧化氮合酶（ Ｎ Ｏ Ｓ）在妊高征发病中的作用,采用免疫组化 Ａ Ｂ Ｃ法分析了３２例妊高征患者胎盘和３２例正常足月孕胎盘中,内皮型一氧化氮合酶（ｅ Ｎ Ｏ Ｓ）和诱导型一氧化氮合酶（ｉ Ｎ Ｏ Ｓ）含量的变化情况。结果：①正常足月孕胎盘和妊高征患者胎盘中均存在ｅ Ｎ Ｏ Ｓ和ｉ Ｎ Ｏ Ｓ抗原,两者均分布于绒毛血管内皮细胞和合体滋养细胞胞浆内;②妊高征患者胎盘中ｅ Ｎ Ｏ Ｓ含量显著低于正常足月孕者（ Ｐ＜ ０．０００５）,且轻度妊高征患者胎盘ｅ Ｎ Ｏ Ｓ含量显著高于中度及重度患者（ Ｐ＜ ０．０２５, Ｐ＜ ０．００５）。妊高征患者的血压与 ｅ Ｎ Ｏ Ｓ含量之间有显著的负相关（ｒ＝ － ０．６０１１, Ｐ＜ ０．０００５）;③妊高征患者胎盘ｉ Ｎ Ｏ Ｓ含量与正常足月孕者无显著差异。轻度与中度、轻度与重度以及中度与重度妊高征患者胎盘ｉ Ｎ Ｏ Ｓ含量均无显著差异。妊高征患者的血压与ｉ Ｎ Ｏ Ｓ含量之间无相关性。以上说明：妊高征患者胎盘中ｅ Ｎ Ｏ Ｓ含量的减少与其发病有关。     

Simvastatin increases the activity of endothelial nitric oxide synthase via enhancing phosphorylation

3-hydroxy-3-methylgulutaryl-coenzyme A （HMG-CoA） reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of Cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase （eNOS）. In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells （293-eNOS） with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin （10 μm/L） for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline （2889.70±201.51 versus 5630.18＋218.75 pmol/min . mg proteins） （P〈0.01）. Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 （ser） and also 495 （thr） but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate,the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.     

Effect of Nitric Oxide on Potassium Channels of Rat Airway Smooth Muscle Cells

Summary: The effect of nitric oxide donor sodium nitroprusside (SNP) on resting membrane potential (Em) and potassium currents of the bronchial smooth muscle cells from rats was investigated. All experiments were conducted in conventional whole-cell configuration. The changes of Em and potassium currents after addition of 0. 1 mmol/L SNP were measured under the current-clamp mode and the voltage-clamp mode respectively. Results showed that (1) SNP could decrease the Em from --33. 8±7.4 mV to -43. 7±6. 7mV (n=10, P＜0. 01); (2) SNP could increase the Ca2+-activated K+ channel peak currents under ramp protocol from 466.9±180. 1 pA to 597. 7±237. 6 pA (n= 7, P＜0. 01), and the currents under pulse protocol at +50 mV were increased from 544.2±145.4 pA to 678.1±206. 2 pA (n=6, P＜0.05); (3) SNP also could increase voltage-gated K+ channel peak currents under ramp protocol from 389. 6±84. 1 pA to 526. 7±98. 7 pA (n=7, P＜0. 01), the currents under pulse protocol at +50 mV were increased from 275.7±85.2 pA to 444.3±128.5 pA(n=6,P＜0. 01). It was concluded that SNP increases the activities of Ca2+-activated K+ channels and voltage-gated K+ channels and leads to K+ efflux and hyperpolarization of the cell membrane, resulting in a decrease of the cell excitement.     

Therapeutic Effect of Propofol in the Treatment of Endotoxin-induced Shock in Rats

Lipopolysaccharide (LPS) ,amaincomponentofgram negativebacterialendotoxin[1] ,istheleadingcauseofsepsisorendotoxicshock ,andwhenadmin isteredexperimentallytoanimals ,mimicsthesameinflammatoryresponse The pathophysiologicalchangesseeninsepsisareoftennotduetotheinfec tiousorganismitselfbuttotheuncontrolledproduc tionofinflammatorymediators ,includingtumornecrosisfactor (TNF) α ,nitricoxide (NO)andneu trophilaccumulation Accumulationoftheseleadstotissuedamage ,ultimately producingthelethalit…     

内皮型一氧化氮合酶基因T786C多态性与原发性高血压的相关关系

目的探讨内皮型一氧化氮合酶(eNOS)基因T786C多态性与中国汉族人原发性高血压(EH)的相关性。方法采用多聚酶链式反应(PCR)结合限制性内切酶片段长度多态分析方法,检测167例健康人和267例高血压患者的eNOS基因T786C多态性,并用硝酸还原酶法测定空腹血清一氧化氮代谢物(NOx)水平,用放射免疫法测定内皮素(ET)的浓度。结果EH组CT+CC基因型和C等位基因频率显著高于对照组(P<0.05);TT基因型的空腹血清NOx浓度[(77.68±33.36)μmol/L]、NOx/ET比(1.41±1.28)明显高于CT+CC基因型[(67.15±24.22)μmol/L、0.93±0.51](P<0.05);TT基因型ET水平[(68.70±29.04)ng/L]明显低于CT+CC基因型[(78.23±31.17)ng/L](P<0.05)。结论eNOS基因T786C多态性的C等位基因与中国汉族人EH的发生相关,C等位基因携带者可能通过减少内皮NO的释放参与EH发病。     

Clinical study on the treatment of premature ejaculation by Uighur medicine Gu-jing-mai-si-ha Tablet (固精麦斯哈片)

Objective:To observe the effect of Uighur medicine Gu-jing-mai-si-ha Tablet (固精麦斯哈片,GJMSHT) for treatment of premature ejaculation (PE) and to explore part of its mechanism. Methods:The condition of patients was scored by related questionnaire,and the intravaginal ejaculation latency time (IELT) was observed before and after GJMSHT treatment,with the blood levels of nitric oxide (NO) and prostaglandin F_(2α)(PGF_(2α)) detected in PE patients as well.The results were compared with those in the control group.Results:After treatment,the scores of PE and IELT,as well as the levels of NO and PGF_(2α) all increased significantly compared to those before treatment in the treated group (P<0.01),while in the control group,all the parameters were insignificantly changed (P>0.05). Therefore,the difference of these parameters between the two groups after treatment all showed statistical significance (P<0.01).Conclusion:GJMSHT could treat PE effectively,its mechanism is possibly by strengthening the coordination of the related smooth muscles through increasing the blood levels of NO and PGF(2α),and the endurance of patients to the cavitary effect of prostatico-urethral pressure,thus postponing the arrival of urgent ejaculatory feeling.     

Effect of Diallyl Trisulfide on the Activation of T Cell and Macrophage－mediated Cytotoxicity

(冯作化)(张桂梅)(郝天玲)(周斌)(张慧)(姜志尧)ＥｆｆｅｃｔｏｆＤｉａｌｌｙｌＴｒｉｓｕｌｆｉｄｅｏｎｔｈｅＡｃｔｉｖａｔｉｏｎｏｆＴＣｅｌｌａｎｄＭａｃｒｏｐｈａｇｅ－ｍｅｄｉａｔｅｄＣｙｔｏｔｏｘｉｃｉｔｙ￥ＦＥＮＧＺｕｏ－ｈｕａ；ＺＨＡＮＧＧｕｉ－...     

Inhibition of Expression of Hypoxia-inducible Factor-la mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

Summary In order to study the effect of nitric oxide (NO) on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L-argine (L-Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF-1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT-PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2.7 mmHg,l mmHg=0.133 kPa) was significantly lower than that in chronic hypoxic group (35.8 ±6.1 mmHg,t=0.2918,P<0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L-argine group (24.4±3.8 mmHg,t=0.2563,P<0.05). ISH showed that the expression of HIF-1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683,t=3.125,P<0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L-argine group (0.1928±0.0381,t=2.844,P<0.05). RT-PCR showed that the content of HIF-1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L-argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF-1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH. AO Qilin, male, born in 1971, Lecturer, M. D., Ph. D. This project was supported by a grant from National Natural Sciences Foundation of China (No. 39730190).     

Impact of luteinized unruptured follicles on endometrial receptivity

This study examined the impact of luteinized unruptured follicle (LUF) on endometrial receptivity. The menstrual cycle of 17 LUF patients (LUF group) and 13 ovulatory women (control group) was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E2 and P were detected by chemiluminescence. The results exhibited that (1) The mean serum P level in LUF group (7.32±2.56 ng/mL) was significantly lower than that in control group (11.17±3.17 ng/mL) (P<0.01). But there was no significant difference in the mean serum E2 levels between LUF group (179.35±81.60 pg/mL) and the control group (198.58±75.23 pg/mL) (P>0.05); (2) The mean expression intensities of ER, PR in endometrium of LUF group (183.86±2.43, 167.94±3.04) were significantly higher than those in control group (109.35±6.31, 105.98±4.07) (P<0.01); (3) The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients (114.90±11.38) were significantly lower than those in control group (191.34±1.82) (P<0.01); (4) The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level (r=0.77, P<0.01), but bore no significant relationship with serum E2 level (r=0.01, P>0.05). It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.     

Modulation of Matrix Metalloproteinase and TIMP-1 Expression by TGF-β1 in Cultured Human RPE Cells

Matrix metalloproteinases(MMPs)are a familyof zinc binding,calcium-dependent endopeptidases thatfunction by degrading extracellular matrix(ECM)components.The functional effects of these enzymesare in part controlled byinteractions withtissueinhibi-tors of metalloproteinases(TI MPs)acting as naturalMMPinhibitors.Aprecise balance between MMPandTI MPactivities may be i mportant for the integrity ofECMcomponents[1].It shows that the expression andactivity of MMPs could be regulated by va…     

Clinical significance of a myeloperoxidase gene polymorphism and inducible nitric oxide synthase expression in cirrhotic patients with hepatopulmonary syndrome

The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO-463 G/A geno...