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Acta Pharmacologica Sinica 2004年第6期25卷 12-18页

作者： Bo HU, Sheng-gang SUN2, E-tang TONGNeurology department, union hospital, Tongji College, huazhong university of science and technology, wuhan 430022, China Neurology department Union Hospital Tongji College Huazhong University of Science and Technology Wuhan 430022

AIM: To study the effect of glutamate on the intracellular calcium signal of pure cultured rat astrocytes and the roleof N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) re-ceptors in the procedure. METHODS: The fluorescence of calcium was measured by Fura-2/AM (F345/F380).RESULTS: L-Glutamate induced [Ca2+]i increase in most of the cells in concentration- and time-dependent *** 50 mmol/L induced the fluorescence increase by almost three to four times, while the effect of AMPA 50mmol/L was just half of that of D-(-)-2-amino-5-phosphonopentanoic acid (D-AP-5; a selective antagonist of theNMDA receptor). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX, a selective antagonist of the AMPA receptor)abolished the effects of NMDA and AMPA, respectively. D-AP-5 and CNQX simultaneously or respectively attenu-ated the effect of L-glutamate at different degrees, but could not abolish it entirely. CONCLUSION: Glutamatemodulated intracellular Ca2+ of pure cultured rat astrocytes through different pathways. The activation of NMDAand AMPA receptors took part in the complex mechanisms.

关键词： glutamate astrocytes NMDA receptors AMPA receptors calcium

Inhibition of ethanol-induced toxicity by tanshinone ⅡA in PC12 cells

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Acta Pharmacologica Sinica 2006年第6期27卷 659-664页

作者： Xian-fang MENG~2 Xiao-jing ZOU~3 Bin PENG~2 Jing SHI~2 Xin-min GUAN~2 Chun ZHANG~(4,5)2.department of Neurobiology,Tongji Medical College,huazhong university of science and technology,wuhan 430030,China 3 department of Anesthesiology,4 department of Nephrology,union hospital,Tongji Medical College,huazhong university of science and technology,wuhan 430022.China department of Neurobiology Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Anesthesiology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To observe the effects of tanshinone IIA(Tan IIA)on the neurotoxicityinduced by ethanol in PC 12 cells and to explore its protective ***:PC 12cell survival was measured by MTT *** formation of reactive oxygenspecies(ROS)and lactate dehydrogenase(LDH)release were detected by 2′,7′-dichlorofluorescin(DCF)fluorescence and calorimetric method,*** of cell apoptosis was monitored by flow *** expression ofp53 was detected by immuno-fluorescence and flow ***:Ethanolsignificantly impaired the survival of PC12 cells as demonstrated by MTT *** also induced significant ROS formation and increased LDH ***-incubation with Tan IIA in the culture medium significantly reversed these *** caused cell apoptosis and the upregulation of p53 *** anti-apoptosis effects of Tan IIA on ethanol-induced toxicity were accompanied by thedownregulation of pro-apoptotic p53 protein ***:Tan IIAcan protect neurons from apoptosis and might serve as a potential therapeuticdrug for neurological disorders induced by ethanol.

关键词： apoptosis ethanol PC12 cells p53 tanshinone ⅡA

Deguelin inhibits expression of IκBα protein in Raji and U937 cells

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Acta Pharmacologica Sinica 2006年第4期27卷 485-490页

作者： Wei-hua CHEN Yan CHEN~2 Guo-hui CUI department of Hematology,union hospital.Tongji Medical College,huazhong university of science and technology,wuhan 430022,China department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To determine whether deguelin can regulate the expression of nuclear factorkappa B(NF-κB)binding protein(IκBα)in U937 human leukemia cells and Rajihuman B lymphoma ***:The localization of IκBα protein was investi-gated by using an immunofluorescence *** expression of IκBα and NF-κB/p65 proteins in Raji and U937 cells were investigated by using Western *** was detected through annexin V/PI double-labeled ***:IκBα localized in the cytoplasm in untreated and deguelin-treated *** with tumor necrosis factor α(TNF-α)or deguelin plus TNF-α for 15 min,there was a substantial reduction in the amount of IκBα *** expressionof IκBα was downregulated by deguelin in Raji and U937 *** inducedapoptosis in U937 ***:Deguelin inhibited the expression of IκBαprotein in U937 and Raji *** anti-proliferative activity of deguelin is relatedto the signal pathway of NF-κB.

关键词： deguelin IkBα nuclear factor kappa B tumor necrosis factor-α apoptosis Raji cells U937 cells

Radioiodine labeled SP-4 as an imaging agent foratherosclerotic plaques

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Nuclear science and Techniques 2000年第4期11卷 234-239页

作者： ZHANG Yong-Xue, WU Zhi-Jian, CAO Wei (union hospital, huazhong university of science and technology, wuhan 430022) 华中科技大学湖北武汉 430022

The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labeled with 131I and 125I by the Chloramine--T method and purified through Sephadex G25 column. Tewlve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR ). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then fed with high cholesterol and fat diet. 125I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125I-SP-4 in rabbits was investigated. The uptakes (%ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macroautoradiography and microautoradiography were performed in 2 AR atheroscle-rotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4hours postinjection were significantly higher than that of NR. The films of macroautoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of microautoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent.

关键词：放射性碘标记 SP-4 临床应用放射性显像药物诊断动脉粥样硬化实验兔动物实验

Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro1

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Acta Pharmacologica Sinica 2005年第10期26卷 1265-1273页

作者： Hong-li LIU~2, Yan CHEN~(2,3), Guo-hui CUI~2, Qiu-ling WU~2, Jing HE~2, Wei-hua CHEN~2, Jian-feng ZHOU~4 ~2.department of Hematology, union hospital, Tongji Medical College, huazhong university of science and technology, wuhan 430022 ~4 department of Hematology, Tongji hospital, Tongji Medical College, huazhong university of science and technology, wuhan 430030, China department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Hematology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim: To investigate the anticancer effects and the molecular mechanisms of deguelin on human U937 leukemia cells, and to explore the underlying mechanism regulating nucleoporin 98 （Nup98） and nucleoporin 88 （Nup88） in vitro. Methods: The effects of deguelin on the growth of U937 cells were studied by MTT assay. The effect of deguelin on the cell cycle of U937 cells was studied by using a propidium iodide method. The localization of the nuclear pore complex proteins Nup98 and Nup88 was investigated by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 and Nup88 in U937 cells was investigated by using flow cytometry and Western blot. Results: The prolif eration of U937 cells was inhibited in the deguelin-treated group, with a 24-h IC50value of 21.61 nmol/L and a 36-h IC50value of 17.07 nmol/L. U937 cells treated with deguelin had reduced percentages of cells in the G0/G1phase, whereas cells accumulated in the S and G2/M phases. Nup88 and Nup98 were found on both the nuclar and cytoplasmic sides of the U937 cells by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 was upregulated and that of the Nup88 protein was downregulated in U937 cells treated with deguelin. Conclusion: Deguelin is able to inhibit the proliferation of U937 cells by regulating the cell cycle such that cells are arrested at the S and G2/M phases, so that the proportion of cells in the G0/G1phase decreases. The antitumor effects of deguelin are related to upregulating the expression of Nup98 and downregulating the expression of Nup88 protein in U937 cells.

关键词： deguelin U937 cells nucleoporin Nup98 Nup88

Antioxidative effect of propofol during cardiopulmonary bypass in adults

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Acta Pharmacologica Sinica 2004年第3期25卷 80-86页

作者： Shi-hai ZHANG2,Shou-yong WANG,Shang-long YAO department of Anesthesiology,union hospital,Tongji MedicalCollege,huazhong universityof science & technology,wuhan 430022,China department of Anesthesiology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan 430022

AIM: To investigate the antioxidative potential of propofol (an intravenous anesthetic with a chemical structure similarto phenol-basedfree radicalscavengers suchas vitaminE) during cardiopulmonary bypass(CPB). METHODS: Thirty adult patients referred for elective cardiac procedure with CPB were included and randomly allocated to a propofol group or a control group. Patients in the propofol group received propofol (0.1 mg·kg-1·min-1) intrave- nously for anesthesia maintenance, whereas those allocated to the control group received fentanyl 10 μg/kg intrave- nously and inhaled enflurane (1 %-1.5 %). Blood samples were collected at 7 time points: before the start of CPB, at 30 and 60 min of CPB, at the conclusion of CPB, 10 min after the administration of protamine, and 12 and 24 h after the cessation of CPB. Plasma levels of free F2-isoprostanes (sensitive markers of free radicals production) and complement C5a were determined by mass-spectrometricassay and enzyme immunoassay, respectively. Neu- trophil adhesion to endothelial cells was observed at ×200 magnificationunder a light microscope. RESULTS: Levels of F2-isoprostanes, complement C5a and neutrophil adhesion rate increased significantly during and after CPB in both groups. There were significantly higher levels of F2-isoprostanes, C5a, and more neutrophils adhering to endothelial cells in the control group than those in the propofol group, respectively. CONCLUSION: Cardio- pulmonary bypass is associated with a great production of damaging free radicals. Propofol may be beneficial both as an anesthetic and as a potent free radical scavenger in patients presenting pathologies associated with free radical reactions during CPB.

关键词： propofol cardiopulmonary bypass free radicals F2-isoprostanes complement 5a

TLR4 signaling induced TLR2 expression in the process of mimic cerebral ischemia/reperfusion in vitro

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中国科学：生命科学英文版 2010年第2期53卷 223-228页

作者： SUN Peng1,ZHANG Qing2,HAN JiYuan1,TIAN Yuan3 & ZHANG JingHui3 1department of Emergency,union hospital,Tongji Medical College,huazhong university of science and technology,wuhan 430022,China 2department of Anesthesia,union hospital,Tongji Medical College,huazhong university of science and technology,wuhan 430022,China 3department of General Surgery,union hospital,Tongji Medical College,huazhong university of science and technology,wuhan 430022,China department of Emergency Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Anesthesia Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of General Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Both TLR4 and TLR2 participated in the mediation of the inflammatory injury in the process of partial cerebral ischemia/***,it still remains unclear whether a crosstalk exists between TLR2 and TLR4 in ischemic cerebral *** the present study,we investigated the effect of TLR4 signaling on TLR2 expression during mimic cerebral I/R in ***-2 cells were cultured and treated with ischemia/reperfusion,then transfected with the plasmid pEGFP-H1/TLR4-siRNA,the plasmid pEGFP-H1/control sequence-siRNA and the blank plasmid,***,the expression of TLR2 and TLR4 mRNA and protein,NF-κB p65 mRNA and supernatant TNF-α level were significantly higher in ischemia/reperfusion treated cells than those lack of ischemia/reperfusion treatment,and as compared with those in ischemia/reperfusion treated cells without transfection,no significant differences about the above mentioned gene and protein expression were found in the blank plasmid tranfected cells and the plasmid pEGFP-H1/control sequence-siRNA transfected cells respectively,while the expression levels in the plasmid pEGFP-H1/TLR4-siRNA transfected cells were significantly ***,in order to determine the effects of pyrrolidinediethyldithiocarbamate (PDTC),an NF-κB inhibitor,on the TLR4-induced TLR2 expression in BV-2 cells treated with ischemia/reperfusion,it was found that TLR4 and TLR2 mRNA expressions in PDTC pretreated cells were significantly lower in comparison with normal saline pretreated cells and non-pretreated *** data suggested that TLR2 activation,signaled by TLR4 and regulated by NF-κB,might be directly involved play an important role in ischemia/reperfusion induced brain damage.

关键词： Toll-like receptor 4 Toll-like receptor 2 cerebral ischemia/reperfusion microglia

Hyaluronic acid fragments evoke Kupffer cells via TLR4 signaling pathway

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science China(Life sciences) 2009年第2期52卷 147-154页

作者： ZHANG JinXiang1, WANG Hui2, XIAO Qing3, LIANG HuiFang4, LI ZhuoYa4, JIANG ChunFang1, WU HeShui5 & ZHENG QiChang5 1 department of Emergency Surgery, union hospital Affiliated to huazhong university of science and technology, wuhan 430022, China 2.department of Medical Genetics, Tongji Medical College Affiliated to huazhong university of science and technology, wuhan 430030, China 3 department of Ophthalmology, union hospital Affiliated to huazhong university of science and technology, wuhan 430022, China 4 department of Medical Immunology, Tongji Medical College Affiliated to huazhong university of science and technology, wuhan 430030, China 5 department of General Surgery, union hospital Affiliated to huazhong university of science and technology, wuhan 430022, China department of Emergency Surgery Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan China department of Medical Genetics Tongji Medical College Affiliated to Huazhong University of Science and Technology Wuhan China department of Ophthalmology Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan China department of Medical Immunology Tongji Medical College Affiliated to Huazhong University of Science and Technology Wuhan China department of General Surgery Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan China

Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acquire the ability to activate immune cells under inflammatory conditions. Here we inves- tigated whether HA fragments could activate Kupffer cells and analyzed the underlying mechanism. Kupffer cells were isolated from wild-type mice (WT, C3H/HeN) and TLR4 mutant mice (C3H/HeJ) and HA fragments were produced by the methods of enzyme digestion and chromatography. Then Kupffer cells were stimulated by HA fragments or other control stimuli. The activation of Kupffer cells was estimated as the release of pro-inflammatory cytokines. The activation of p38 MAPK pathway of Kupffer cells was checked and blocking experiments were done as well. The results indicated that HA fragments acquired the ability to activate Kupffer cells in vitro, which was TLR4 dependent and not due to contamination of lipopolysaccharide. Experiments of p38 MAPK kinase inhibition by SB-203580 verified p38 MAPK was required in HA fragments induced Kupffer cells activation. This suggests that HA fragments, degradative products of one of the major glycosaminoglycans of the extracellular matrix, play critical roles in Kupffer cell activation mediated by TLR4 signaling pathway, which is, at least partially, de- pendent on p38 MAPK activation.

关键词： Kupffer cells hyaluronic acid fragments toll-like receptor 4 p38 MAPK lipoplysaccharide reperfusion injury liver

Exact eigenstates for a class of models describing multiphoton processes in the presence of seven bosonic modes

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science China(Physics,Mechanics & Astronomy) 2004年第6期47卷 649-657页

作者： ZHAN Zhiming1,LI Weibin2,YOU Jun2,XIE Xiaotao2 & YANG Wenxing2 1.State Key Laboratory of Laser technology,huazhong university of science and technology,wuhan 430074,China 2.department of Physics,huazhong university of science and technology,wuhan 430074,China State Key Laboratory of Laser technology Huazhong University of Science and Technology Wuhan 430074 China department of Physics Huazhong University of Science and Technology Wuhan 430074 China

We present the analytical expressions of eigenstates and eigenenergies by using a parameter λ without the assumption of Bethe anzatz for three kinds of seven-bosonic-mode mixing models. The parameter is shown to be determined by the roots of a simple polynomial. We also demonstrate the exact analytical expressions of eigenstates and energies without any unknown parameter.

关键词： spectra, eigenstate, eigenvalue.