李小强；招明高；梅其柄；张延凤；曹蔚；王海芳；陈丹；崔毅
AIM: To investigate the effect of nicotine on 1β1-adrenergic receptor (β1-AR) in the hippocampal slice of rat. METHODS: Hippocampal slices (400 μm thick) were incubated in artificial cerebrospinal fluid (ACSF) previously saturated with 95 % O2 and 5 % CO2 at 28 ℃ for 120 min, and then incubated with nicotine 10 μmol/L for 30, 60, 90, and 120 min. mRNA of the β1-adrenergic receptor was examined with semiquantitative reverse transcriptionpolymerase chain reaction (RT-PCR), and the protein level was measured by Western blot and RIA. RESULTS: The mRNA gene expression and the protein level of β1-adrenergic receptor in hippocampal slices were increased after nicotine treatment. The peak of protein occurred later but higher than that of mRNA level. CONCLUSION:Both expression of β1- adrenergic receptor gene transcription and post-transcriptional protein level in rat hippocam pus were altered by nicotine.
作者：王勇；朱小南；颜杰；余剑平；黄晓卉；陈汝筑 刊期： 2003年第12期
AIM: To investigate the possible effect of nitric oxide on receptivity and apoptosis of mouse endometrium and the possible pathway. METHODS: Female pregnant mice were treated with either molsidomine, a generator of nitric oxide (NO), or N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. The pregnancy rates of each group were calculated; 3'-end-labeling was used to detect DNA fragmention of apoptotic cells; immunohistochemistry, in situ hybridization, and Western blot were applied respectively to estimate expression levels of Fas/FasL proteins and mRNA. RESULTS: The pregnancy rate in the drug treated group was reduced in a dose-dependent manner; apoptosis, Fas protein and mRNA levels in the endometrium of drug treated mice were correlatively decreased during the peri-implantation period. CONCLUSION: The decreased pregnant rate in mice by abnormal levels of nitric oxide may be brought about by inhibiting the normally occurrence of apoptosis in the receptive endometrium.
作者：魏鹏；苑金香；金萱；胡召元；刘以训 刊期： 2003年第12期
AIM: To study the relationship between genotype of CYP2D6*10B and pharmacokinetics of propafenone enantiomers. METHODS: Genotype of 17 healthy Chinese HAN subjects was determined by an allele specific amplification method. The blood samples (0-15 h) of the subjects were taken after oral administration of a single dose (400 mg) of propafenone hydrochloride. Concentrations of propafenone enantiomers in plasma were mea sured by a reverse-phase HPLC with precolumn derivatization. RESULTS: Seventeen subjects characterized for CYP2D6* 1 0B genotype included (* 1/* 1) (n = 4), (* 1/* 10) (n = 5) and (* 10/* 10) (n = 8). The metabolic ratios (lg MR) of the three genotypes were -2.68+0.23, -2.2+0.7, and -1.1 +0.5, respectively. The AUC of the three groups that of *1/*10 group or *1/*1 group, and the CL of both enantiomers in *10/*10 is only half of that of *1/*10 group or * 1/* 1 group (P＜0.05). CONCLUSION: CYP2D6* 10B alleles induce the declined activity of CYP2D6 and impair the metabolism of propafenone.
作者：陈冰；蔡卫民 刊期： 2003年第12期
AIM: To determine survival and differentiation of cultured neural stem cells (NSCs) into viable and functional neurons upon transplantation into mice brain of MPTP-induced Parkinson disease (PD). METHODS: Mouse model of PD was established with two subcutaneous (sc) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 40 mg/kg) twice, 16 h apart. NSCs isolated from rat embryo midbrain were cultured in clonal density.After labeled with 5-bromo-2'-deoxyuridine (BrdU), the NSCs were transplanted into the uni- or bi-lateral striatum of PD mouse. Tyrosine hydroxylase (TH) immunofluorescence was used to evaluate the toxicity of MPTP on theneural cells in the substantia nigra. Immunohistology and laser confocal microscope were used to detect the survival and differentiation of transplanted NSCs. RESULTS: The cultured NSCs generated neurospheres and differentiated into neuron and astrocyte. It indicated that the cultured NSCs were multipotent and self-renewal in vitro.TH-positive neural cells were significantly reduced in the substantia nigra. Immunohistology showed that the uni- or bi-lateral transplanted NSCs survived in the brain of PD model mouse. Laser confocal microscope indicated that some transplanted NSCs could properly differentiate into targeted TH-positive neural cells in vivo. CONCLUSION:The transplanted multipotent NSCs could survive and differentiate into functional dopamine neurons.
作者：李学坤；郭安臣；左萍萍 刊期： 2003年第12期
During the past several decades, clinical investigators world-wide have continued to study the causes,pathophysiology, and treatment strategies for acute lung injury (ALI). This syndrome, which is characterized by nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, is slowly becoming better understood as a result of these efforts.
作者：Roger G SPRAGG 刊期： 2003年第12期
AIM: To investigate the role of Fas-FasL pathway in the pathogenesis of streptozotocin (STZ)-induced type I diabetes mellitus. METHODS: Low dose injections of STZ were used to induce type I diabetes mellitus in the CMV-hFasL transgenic mice. Blood glucose concentration was measured with Glucotrand Plus blood glucose test strips. Expression of hFasL was detected by RT-PCR and Western blotting. The severity of insulitis was determined by histologicalexamination. Expressions of IL- 1 β and TNF-α mRNA in the pancreas were detected by semi-quantitative RT-PCR analysis. Fas expression in apoptotic RIN-5F cells was also confirmed by RT-PCR in vitro. RESULTS: hFasL was expressed in the islets of CMV-hFasL transgenic mice. The transgenic mice were sensitive to diabetic induction than the control WT mice. IL-1 β and TNF-α expressions in the pancreas of CMV-hFasL transgenic mice were far more than that in WT mice. We also found STZ and IL-1β could both induce higher expression of Fas in RIN-5F. The combining of Fas-FasL could lead to the apoptosis of β cells in the CMV-hFasL transgenic mice. CONCLUSION: Fas-FasL interaction plays a significant role in the pathogenic mechanism of type I diabetes mellitus.
作者：林波；章振林；余路阳；郭礼和 刊期： 2003年第12期
The emergence of nucleic acid-based molecular techniques has significantly enhanced laboratory diagnosis and monitoring of atypical pneumonia. These techniques have not only provided rapid and sensitive detection of fastidious microbial organisms but have also played critical roles in identifying and characterizing emerging patho gens that cause atypical pneumonia. Other benefits that molecular techniques can bring to the field include organ ism differentiation, quantitation, typing, and antibiotic resistance profiles. Gradually becoming standardized and widely available, the future will see some promising molecular methods become a mainstay in clinical laboratories for recognition and diagnosis of atypical pneumonia pathogens.
作者：Tang YW 刊期： 2003年第12期
AIM: To determine whether ONO-1078 {pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy)benzoyl-amono]-2-(tetrazol 5-yl)-4H-1-benzopyran hemihydrate}, a potent leukotriene receptor antagonist, possesses a neuroprotective effect on global cerebral ischemia in rats, and to explore its possible mechanism of action. METHODS: Transient global cerebral ischemia was induced by four-vessel occlusion for 10 min and followed by 72-h reperfusion. ONO-1078 (0.03-0.3 mg/kg) and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one, a neuroprotective agent) 10 mg/kg were ip injected 30 min before ischemia and 1 h after reperfusion, and once a day afterward. Neurological outcome was evaluated before ischemia and 24, 48, 72 h after reperfusion. Neuron density, the expressions of N-methyl-D aspartate (NMDA) receptor subunit proteins (NR1, NR2A, NA2B) and vascular cell adhesion molecule 1 (VCAM-1) in the cerebral cortex and hippocampus were measured at 72 h after reperfusion. RESULTS: ONO-1078 (0.1, 0. 3 mg/kg) and edaravone (10 mg/kg) improved ischemia-induced neurological deficiency and reduced neuron death. ONO-1078 (0.1, 0.3 mg/kg) significantly inhibited the enhanced expression of NMDA receptor subunit protein NR2A in the cortex and VCAM-1 in the hippocampus of ischemic rats. CONCLUSION: ONO-1078 possesses a neuroprotective effect on global cerebral ischemia in rats, and its mechanism may be partly related to the inhibition of the upregulation of NR2A and VCAM- 1 in different regions of the brain.
作者：张丽慧；魏尔清 刊期： 2003年第12期
AIM: The characteristics of transepithelial transport and uptake of CPU-86017 {[7-(4-chlorbenzyl)-7,8,13,13α tetrahydroberberine chloride, CTHB] }, a new antiarrhythmia agent and a new derivative of berberine, were investi gated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives. METHODS: Caco-2 cell was used. RESULTS: 1) The permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitor-cyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5 mg/L had no effect on the transepithelial electrical resistance (TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfac tants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100 μmol/L and low pH (pH=6.0) induced a reversible decrease of TEER; enhancements of the transepithelial transport of CPU-86017 were also observed with some surfactants; 2) In the process of uptake of CPU-86017, the initial uptake rates of CPU-86017 were saturable with a Vmax of (250+39) μg.min-1.g-1 (protein) and Km of (0.90+0.12) mmol/L. This process was enhanced by cyclosporine A (7.5 mg/L) with a Vmax of (588+49) μg.min-1.g-1 (protein) and Km (0.42+0.08) mmol/L. CONCLUSION: Some surfactants and P-gp inhibitors can be considered as enhancers of its transepithelial trans port and uptake.
作者：杨海涛；王广基 刊期： 2003年第12期
INTRODUCTIONPhospholipases A2 (PLA2s) belong to a family of enzymes that hydrolyze phospholipids at the sn-2 posi tion leading to the liberation of fatty acids andlysophospholipids (Fig 1).
作者：Touqui L；WU YZ 刊期： 2003年第12期
AIM: To evaluate the anti-inflammatory effect of methoxyphenamine compound (MC) on chronic obstructive pulmonary disease (COPD) in rats by measurement of proinflammatory cytokines, total and differential white cell counts (WCC) of bronchroalveolar lavage fluid (BALF). METHODS: Adult rat model of COPD (COPD group) was induced by intratracheal instillation of lipopolysaccharides and exposure to cigarette smoke. Treatment groups received different dosage of MC (3, 9, and 27 mg daily, MC group) or prednisone (0.25 mg daily, P group) respectively. Tumor necrosis factor alpha (TNF-α), interleukin lbeta (IL-1 β), interleukin-6 (IL-6), transforming growth factor β (TGF-β) of BALF were determined by ELISA. Total and differential WCC were performed after Giemsa staining. RESULTS: The levels of TNF-α, IL-1 β, IL-6, TGF-β, total and differential WCC in BALF of MC groups were significantly decreased than that of COPD group (P＜0.01), and there was no significant difference among MC groups. There was no significant decrease in the levels of TNF-α, IL-1β, and count of alveolar macrophages in P group compared to those of COPD group. More significant decrease in total WCC and neutro phils was found in P than in COPD group (P＜0.01). CONCLUSION: MC has anti-inflammmatory effect in the rats with COPD.
作者：王悦红；白春学；洪群英；陈杰 刊期： 2003年第12期
COLLECTINS AND INNATE IMMUNITYPulmonary surfactant comprises two hydrophobic proteins SP-B and SP-C, which are important for the adsorption and spreading of the surfactant film at the air-liquid interface[1].
作者：Haagsman HP；Herias V；van Eijk M 刊期： 2003年第12期
AIM: To study the effect of puerarin (Pue) on Na+ channel in rat ventricular myocytes. METHODS: Whole-cell patch-clamp technique was applied on isolated cardiomyocytes from rats. RESULTS: Pue inhibited cardiac INa in a positive rate-dependent and dose-dependent manner, with an IC50 of 349 μtmol/L. The kinetics of blockage ofcardiac sodium channel by Pue resembled the ClassIa/Ic of antiarrhythmic agents. Pue 300 μmol/L did not alter the shape of the I-V curve of INa, but markedly shifted the steady-state inactivation curve of INa towards more negative potential by 15.9 mV, and postponed the recovery of INa inactivation state from (21.9+ 1.6) ms to (54.4+3.4) ms (P＜0.01). It demonstrated that the steady state of inactivation was affected by Pue significantly. CONCLUSION:Pue protected ventricular myocytes against cardiac damage and arrhythmias by inhibiting recovery from inactivation of cardiac Na+ channels.
作者：张广钦；郝雪梅；戴德哉；付昱；周培爱；吴才宏 刊期： 2003年第12期
AIM: To explore the possible mechanism of β-amyloid (Aβ)-induced apoptosis in rat cortical neurons and the protective effect of ginsenoside Rg1. METHODS: AO-EB staining was used to quantify the apoptotic cells. DNA fragmentation was observed by gel electrophoresis. The levels of cyclin-dependent kinases-4 (CDK4) and phosphorylated pRB were detected by Western blot. RT-PCR was used to examine the expression of E2F1 mRNA. RESULTS: Treatment with A1-40 at the concentration of 20, 40, 80 mg/L for 48 h induced rat cortical neuron apoptosis from 12.5 %+1.5 % (control) to 22.3 %+1.4 %, 38.8 %+1.3 %, 36.7 %+1.4 %, respectively. Pretreat ment with Rg1 at the dose of 0.5, 1, 2, 4, 8, 16 μmol/L for 24 h, then treatment with A~-40 40 mg/L for 24 h, the percentage of apoptotic neurons decreased from 38.8 %+1.3 % to 14.5 %+1.3 %, 13.3 %+1.0 %, 11.6 %+0.29 %, 11.8 %+ 1.0 %, 6.2 %+0.8 %, 5.8 %+0.8 %, respectively. After treatment with Aβ1-40 40 mg/L for 24 h, there were transient increases in CDK4 and phosphorylated pRB protein level, as well as the expression of E2F1 mRNA. However, the above levels decreased markedly after pretreatment with Rg1 8 μmol/L for 24 h. CONCLUSION: Ginsenoside Rg1 attenuated Aβ1-40-induced apoptosis in rat cortical neurons via inhibiting the activity of CDK4, decreasing the phosphorylation of pRB and downregulating the expression of E2F1 mRNA.
作者：陈晓春；陈丽敏；朱元贵；方芳；周宜灿；赵朝晖 刊期： 2003年第12期
AIM: To study the blockade of paeoniflorin (Pae) on INa in the acutely isolated hippocampus neurons of mice.METHODS: The whole-cell patch clamp technique was used. RESULTS: Pae inhibited INa in frequency-dependentand concentration-dependent manners, with an IC50 of 271 μmol/L. Pae 0.3 mmol/L shifted the activation potential of the maximal INa from -40 mV to -30 mV, shifted the steady-state activation and inactivation curves toward more positive and negative potentials byl0.8 mV, and 18.2 mV, respectively, and postponed the recovery of INa inactivation state from (4.2+0.7) ms to (9.8± 1.2) ms. CONCLUSION: Pae inhibited INa in mouse hippocampus neurons.
作者：张广钦；郝雪梅；陈世忠；周培爱；程和平；吴才宏 刊期： 2003年第12期
Every year, millions of patients worldwide receive ventilator support during surgery. Mechanical ventilation has become an important therapy in the treatment of patients with impaired pulmonary function and particularly in patients suffering from adult respiratory distress syndrome (ARDS). ARDS is caused by multiple factors and is characterized by respiratory dysfunction including hypoxemia and decreased lung compliance. It is known that the decrease in lung distensibility is due to a disturbed surfactant system with an elevated surface tension. This increase in surface tension leads to an increase in forces acting at the air-liquid interface, resulting finally in end expiratory collapse, atelectasis, an increase in right-to-left shunt and a decrease in PaO2.
作者：Haitsma JJ；Lachmann RA；Lachmann B 刊期： 2003年第12期
AIM: To investigate the ability of an antisense RNA eukaryotic expression plasmid pcDNA3.1/survivin in downregulating the expression level of survivin mRNA and survivin protein and reversed multidrug resistance (MDR) in adriamycin-resistant HL-60/ADR cell line. METHODS: The expression of survivin mRNA was measured by RTPCR and the expression of survivin protein was measured by Western blot. Caspase-3 activity was determined by Phar Mingen colorimetric assay kit. Apoptosis was assessed by flow cytometry. The chemosensitivity of HL-60/ ADR ceils to adriamycin (ADR) was measured by MTT assay. RESULTS: pcDNA3.1/survivin down-regulated the expression level of survivin mRNA and survivin protein obviously, and induced apoptosis of HL-60/ADR cells in a time-dependent manner during 12-48 h. After transient transfection with pcDNA3.1/survivin for 48 h, survivin mRNA decreased by 67 %, survivin protein decreased by 57 %, caspase-3 activity increased 4.37 times, and the apoptosis rate increased by 4.41% compared with control. Compared with ADR alone, pcDNA3.1/survivin significantly reversed MDR in HL-60/ADR cells, the chemosensitivity of HL-60/ADR cells to ADR was increased to 5.36folds. CONCLUSION: pcDNA3.1/survivin down-regulated the expression level of survivin mRNA and survivin protein obviously, the threshold of apoptosis was decreased and MDR was reversed.
作者：王磊；张桂梅；冯作化 刊期： 2003年第12期
Inhaled nitric oxide (iNO) has now been used clinically since 1991, or twelve years. The acute aims of therapy have mainly been improvement of oxygenation and reduction of lung vasoconstriction. This is true also for the use in ALI (acute lung injury) of various degrees of severity including ARDS (acute respiratory distress syndrome).
作者：Frostell CG 刊期： 2003年第12期
AIM: To compare the effects of moxonidine (Mox), clonidine (Clo), agmatine (Agm), and xylazine (Xyl) on action potentials (AP) of the rabbit sinoatrial node (SAN) pacemaker cells and investigate the contribution of α-adrenoceptors to the cardiac electrophysiologic responses induced by the agonists. METHODS: Intracellular microelectrode technique was used to record AP in the rabbit SAN pacemaker cells. Vasoconstrictive responses to norepinephrine (NE), Mox, Clo, Agm and Xyl were observed in the thoracic aorta and ear vein isolated from rabbits. RESULTS: (1) In the rabbit thoracic aorta, a rank order of potency producing vasoconstrictive responses was NE＞Clo＞Mox;and a rank order of potency in ear vein was Clo＞NE＞Xyl=Mox. Agm did not produce any vascular responses in both preparations, and Xyl did not produce vascular responses in the thoracic aorta. (2) Mox, Clo, Xyl, and Agm concentration-dependently decreased the rate of pacemaker firing (RPF), and prolonged APD50 and APD90 in the rabbit SAN pacemaker cells. The rank order of decreasing RPF or prolonging APD was Clo＞Xyl=Mox. (3) Most effects of Clo were partially inhibited by yohimbine, but those of Xyl and all the effects of Agm on the AP in SAN pacemaker cells were not affected by the treatment with yohimbine. (4) In the presence of propranolol 1 μmol/L, phenylephrine did not cause any effects on AP in the rabbit SAN pacemaker cells. CONCLUSION: Like Mox, Clo changes AP of the rabbit SAN pacemaker cells via α2-adrenoceptors partially, but the effects of Xyl and Agm on the AP are almost not related to α2-adrenoceptors. Moreover, there are no obviously functional α1-adrenoceptors in the rabbit SAN pacemaker cells.
作者：赵丁；任雷鸣 刊期： 2003年第12期
AIM: To investigate the role of quercetin (Que) in the proliferation of cultured human skin microvascular endothelial cells (MVEC). METHODS: Cell count and [methyl-3H]thymidine ([3H]TdR) uptake assay were used to measure the effect of Que in the proliferation of cultured MVEC. Cytotoxicity of Que on MVEC was also evaluated by 51Cr release assay. RESULTS: When MVEC were treated with Que, the proliferation was significantly inhibited in a time-course and dose-dependent manner. Que 5 μmol/L did not inhibit the proliferation of MVEC. When the concentration of Que increased to 20, 40, 80, and 160 μmol/L, the cell numbers per well were decreased and the inhibition rate was 12.2 %, 23.5 %, 35.3 %, and 54.1% respectively with IC50 of 138 μmol/L. The inhibitory rate of [3H]-TdR uptake was 18.7 %, 34.4 %, 48.9 %, and 62.5 % respectively (ICs0=87.5 μmol/L). 51Cr release assay showed that Que 160 μmol/L incubated with MVEC from 1 to 16 h had no clear cytotoxicity compared with control group. CONCLUSION: Que greatly inhibited the proliferation of cultured human MVEC in vitro. This effect may not be related to the cytotoxicity of Que on MVEC.
作者：范盘生；顾振纶；盛瑞；梁中琴；王晓霞；朱益 刊期： 2003年第12期
中国药理学报（英文版）杂志
主管:中国科学技术协会
主办：中国药理学会和中科院上海药物研究所
