1.Mechanism of M-current modulation by neural transmitters
Academic Journal of Second Military Medical University 1985;0(05):-
M channel, a voltage-dependent potassium channel, has been found in a variety of neurons. It is activated near the threshold of neuron action potential,producing a primary K~+ current, namely the M-current. The M-current can be modulated by many neurotransmitters and hormones, which can influence neuron excitability, conduction and neurotransmitter release. This review discusses the signal transduction pathway from G_~ q/11 activation to intracellular calcium, membrane phospholipid and phosphokinase, and explains the mechanism of M-current modulation by neurotransmitters.
2.The Cultivation of Harmonious Employment Ethics of Medical Students
Chinese Medical Ethics 1996;0(01):-
Combining with the disharmonious ethical phenomena in employment of medical students at present,this paper analyses its subjective and objective reasons,and puts forward some practical approaches to the cultivation of harmonious employment ethics of medical students.
3.Setting up the Ideology of Humanism to do Better Employment of Medical Graduate
Qingzhong PAN ; Aiqin ZHANG ; Ruirong WEI
Chinese Medical Ethics 1996;0(01):-
Combing with the ideology of humanism to expound the intention of the ideology of humanism in the employment work of graduate. Advancing the thinking and practice to carry out the ideology of humanism in the employment work of graduate.
4.Investigation on 6 genetical traits in Yi and Bai ethnic groups in Guizhou province
Qingzhong ZHANG ; Guoqin SONG ; Yuesheng YU
Basic & Clinical Medicine 2006;0(06):-
Objective To study distributive frequencies and the corelation among 6 genetical traits in Yi and Bai ethnic groups in Guizhou province. Methods According to the techniques of human population genetics and cluster random sampling,a survey on 6 genetical characters of 879 cases (Yi ethnic group 472 and Bai ethnic group 407) was carried out in October 2008,then dealt with data using SPSS13.0 software. Results The distributive frequencies in 6 dominant traits of Yi ethnic group are 20.6%,34.3%,74.4%,76.3%,25.4% and 60.8% respectively; Those of Bai ethnic group are 17.2%,39.3%,64.9%,86.2%,15.5% and 66.8% respectively. There are very significant differences(P
5.Mechanism of anti-apoptotic action of dipfluzine on neuronal damage of the rat hippocampal CA1 region subjected to transient forebrain ischemia
Yingjun ZHANG ; Yang GUO ; Qingzhong JIA ; Yongli WANG ; Hailin ZHANG
Acta Pharmaceutica Sinica 2005;40(2):97-104
Aim To explore the relations between anti-apoptotic role of dipfluzine (DIP) and the death signaling transduction pathway initiated by CD95 molecules, and the transcription factor involved in the transcription regulation of CD95 molecules in the hippocampal CA1 region after transient forebrain ischemia. Methods The rat forebrain transient ischemia model was established through 15 min ischemia followed by 3 days reperfusion by using the four-vessel method. The rats were divided randomly into five groups: sham control group, ischemia / reperfusion (I/R) group, DIP treated groups (20, 40 and 80 mg·kg-1 body weight, ig, separately). Western blotting and RT-PCR were performed to detect the expression changes of Fas, FasL, caspase 10 p20, caspase 8, I-κB-α, and p-I-κB-α molecules in protein and mRNA levels, separately, and immunohistochemistry for molecular localization of Fas and FasL in rat hippocampus. Results The expression of Fas, FasL, and caspase 10 p20 in protein and mRNA levels increased after I/R, which was inhibited significantly after treatment with 20 and 40 mg·kg-1 of DIP (P<0.01). In 80 mg·kg-1 of DIP group, the expression of Fas and FasL protein was not significantly different from that of I/R group (P>0.05). The expression of caspase 8 and I-κB-α showed no significant differences in all groups (P>0.05), and no gene expression was observed for p-I-κB-α protein in the study. DIP significantly affected molecular distribution of Fas and FasL protein in CA1 subregion of hippocampus. Conclusion DIP inhibits the death signaling transduction pathway initiated by CD95 molecules in rat hippocampal CA1 subregion, and NF-κB transcription factor may not be involved in the transcription regulation of CD95 molecules after transient forebrain ischemia.
6.Characteristics of KCNQ2/3 potassium channel current and its modulation by M_1 receptor
Qingzhong JIA ; Zhanfeng JIA ; Yingjun ZHANG ; Boyi LIU ; Hailin ZHANG
Chinese Pharmacological Bulletin 2003;0(10):-
Aim To study the characteristics of KCNQ2/3 potassium channel expressed in CHO cells and its modulation by M_1 receptor.Methods KCNQ2 and KCNQ3 potassium channels and M_1 receptor were co-expressed in CHO cells.Whole cell patch-clamp techniques was used to observe the characteristics of KCNQ2/3 current,its modulation by the M_1 receptor,and the effects of the common potassium channel blockers.Results KCNQ2/3 current recorded in CHO cells was a slow-activation low-threshold non-inactivating,voltage-dependent outward potassium current.KCNQ2/3 current was elicited at about-60 mV,V_(1/2)(-26.8?1.2) mV and the deactivation current fitted two exponential function,with ?_(fast) of 101ms and ?_(slow) of 309 ms.The channel was not sensitive to common pharmacological blockers such as 4-AP,Ba~(2+) and TEA,but was inhibited significantly by linopirdine,with a IC_(50) of(6.5?0.83) ?mol?L~(-1).Acetylcholine suppressed the KCNQ2/3 current reversibly via M_1 receptor,with a IC_(50) of(0.7?0.05) ?mol?L~(-1).Conclusion KCNQ2 and KCNQ3 channels are the molecular basis of M-current observed in neuronal cells.KCNQ2/Q3 current expressed in CHO cells has similar characteristics as that seen in neuronal M-current.Linopirdine is a powerful blocker of KCNQ2/3 channel and acetylcholine inhibits the current by muscarinic M_1 receptor.This experiment has laid a solid basis for further study of M-current and KCNQ2/3 current,and is important for the study of neurological diseases relating to alteration of M-current,such as convulsion,epilepsy and Alzheimers disease.
7.Pharmacokinetic study of QO-58:a new potassium channel opener
Canfang LIU ; Jinlong QI ; Hailin ZHANG ; Qingzhong JIA
Chinese Pharmacological Bulletin 2014;(4):574-577
Aim To develop a sensitive, specific and accurate method for the pharmacokinetic study of QO-58 ( a novel M channel opener ) in rats after intragas-tric ( ig) and intravenous ( iv) administration. Meth-ods QO-58 was administered at the doses of 25,50, 100 mg · kg-1 ( ig ) and at single dose of 100 mg · kg-1(iv), respectively. Blood samples were obtained at intervals after each administration. Plasma samples were deproteinized with acetonitrile after addition of in-ternal standard, and detected by RP-HPLC. The main parameters of pharmacokinetics were calculated by DAS2. 1. 1 software. Results The calibration curve in plasma was linear over the range of 0. 1 ~160 mg · L-1 in rat plasma, and the limit of detection ( LOD) was 0. 1 mg · L-1 . The intra-day and inter-day RSD was less than 20%. The recovery of QO-58 in rat plas-ma was 89. 56% ~101. 38%. The concentration-time curves of QO-58 in rat palsma were consistent with the two-compartment model after both oral and intravenous administration. The main pharmacokinetic parameters for QO-58 following oral administration with three doses (25, 50, 100 mg· kg-1 ) in rat were as follows:Cmax (mg·L-1):8.25,16.29,18.27;T12β(h): 8.24, 5. 01, 5. 92; AUC0-∞ ( g · min · L-1 ):261. 94, 189. 57,90. 65. Conclusion The developed method is simple and specific, and is suitable for preclinical pharmacokinetic studies of QO-58 .
8.Role of PTEN on Proliferation of Airway Smooth Muscle Cells in Asthmatic Rats
Qingzhong LI ; Yuling LI ; Feng TIAN ; Haiyun LUAN ; Shuping ZHANG
Tianjin Medical Journal 2009;37(10):869-871,后插4
Objective:To investigate the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in regulating proliferation of airway smooth muscle cells in ovalbumin(OVA)-induced asthma rats. Methods:Male Wistar rats (n=16) were randomized into OVA-induced asthma group and control group(8 rats each). The histomorphological changes of bronchia and lung tissues were observed by H-E staining. The expressions of proliferating cell nuclear antigen(PCNA) and PTEN were assayed by immunohistochemistry. Reverse transcription-polymerase chain reaction(RT-PCR) was carried out to determine the changes in the expression of PTEN mRNA. Results: The typical pathological features of asthma were revealed in the OVA-exposed rats including numerous inflammatory cells infiltrated around the bronchia and in the lung tissues, the thickened airway smooth muscle and the narrowed airway. The levels of PCNA were distinctly increased in OVA-induced asthma group than that of control(P < 0.05),while the levels of PTEN and PTEN mRNA were significantly decreased in lung tissues of OVA-exposed rats(P < 0.05). Conclusion:The gene inactivation of PTEN may play a pivotal role in proliferation of airway smooth muscle cells in asthma rats, and the most probable mechanism is associated with the functions of PI3K signaling pathway.
9.Modulation of KCNQ2 and KCNQ3 potassium channels by extracellular pH
Qingzhong JIA ; Chuan WANG ; Xiaona DU ; Fang LI ; Hailin ZHANG
Chinese Pharmacological Bulletin 1987;0(01):-
Aim To study the modulation of KCNQ2/3 potassium cha nn els by extracellular pH.Methods In vitro transcription was used to synthesize cRNA of KCNQ2/3 potassium channels.The cRNA was injected into Xenopus oocytes to express the KCNQ2/3 channel.The modulation of KCNQ2/3 potass ium channels by extracellular pH was studied by two electrodes voltage clamp tec hniques.Results KCNQ2/3 currents were inhibited and current-vo ltage relationship of activation were shifted to the right with decreased extrac ellular pH. pH modulation of KCNQ2/3 currents was voltage dependent,with a more pronounced effect at more negative potentials above the activation threshold (-60 mV). Extracelluar pH also decreased activation and deactivation kinetics of KCNQ2/3 currents.Conclusion KCNQ2/3 channels, known to contr ibute to neuronal excitability, were modulated by extracelluar pH. The profound effects of the extracelluar pH exerted on KCNQ2/3 channel may play an important role during physiology neuronal activity and pathological events such a s epileptic seizures, cerebral ischemia and shock etc.
10.Spatiotemporal dynamics of pharmacological modulation of membrane PtdIns(4,5)P_2 metabolism by different agents
Chuan WANG ; Qingzhong JIA ; Xiaona DU ; Hailin ZHANG
Chinese Pharmacological Bulletin 1987;0(01):-
Aim To visualize the dynamics of PtdIns(4,5)P 2 hyd ro lysis and resynthesis, and modulate it by pharmacological agents wortmannin, LiC l, U73122 and neomycin. Methods We used a fusion construct of g reen fluorescent protein(GFP) with the PH domain of phospholipase C ?1(PL C ?1PH)(PLC ?1PH-GFP) known to bind PtdIns(4,5)P 2 specifically , and laser-scanning confocal microscopy to trace PtdIns(4,5)P 2 translocatio n. Results Stimulation of endogenous P 2Y receptors by ATP in CHO cells induced a reversible PLC ?1PH-GFP translocation, indicating Pt dIns(4,5)P 2 hydrolysis through the receptor-mediated phospholipase C (PLC) ac tivation. Wortmannin and LiCl did not affect the translocation of PLC ?1PH -GFP from plasma membrane to cytosol but blocked the recovery after the translo cation. The transient translocation from plasma membrane was blocked by the PLC inhibitor U73122 but was not affected by another PLC inhibitor neomycin. However , in the absence of PLC ?1PH-GFP expression, neomycin inlibited the recep tor-induced PLC hydrolysis of PtdIns(4,5)P 2.Conclusion PLC ?1PH-GFP can be used as a valuable fluorescence probe to visualize the dyn amic change of PtdIns(4,5)P 2 in living cells. Wortmannin, LiCl, U73122 and neo mycin have distinct modulation effects on PtdIns(4,5)P 2 metabolism. PLC ?1 PH,when bound to PtdIns(4,5)P 2,prevents neomycin from inhibiting PLC hydro lyzing PtdIns(4,5)P 2.