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Acta Pharmacologica Sinica 2006年第9期27卷 1159-1164页

作者： Jin QIN Zheng-xiang LIU~1 Department of Cardiology,tongji hospital,tongji medical college,huazhong university of science and technology,wuhan 430030,china Department of Cardiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To examine the inhibitory effect of FAK-related nonkinase(FRNK)in cardiachypertrophy in vitro and investigate the possible ***:A func-tional fragment of FRNK cDNA was amplified by reverse transcription-polymerasechain reaction and cloned into the vector *** in neonatal ratcardiac myocytes was established with angiotensin-Ⅱ *** pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes byLipofectamine *** surface area and mRNA expression of atrial natriureticpeptide(ANP)of myocytes were employed to detect cardiac ***-κBp65 protein in nuclear extracts,phosphorylation levels of ERK1/2(p-ERK 1/2)andAKT(p-AKT),as well as total ERK1/2,and AKT in variant treated cardiomyocyteswere determined by Western ***:Under the stimulation of angiotensin Ⅱ,the surface area of myocytes and levels ofANP mRNA were significantly *** transient transfection with pcDNA3.1-FRNK in advance may reduce the sur-face area and expression of ANP mRNA of hypertrophic *** proteinlevels of NF-κB p65 in nuclear extracts and p-ERKI/2,p-AKT in FRNK treatedcardiomyocytes were significantly decreased compared with that in angiotensin-Ⅱ induced cardiomyocytes,while different treatments had little effect on totalERK1/2 and ***:FRNK may inhibit angiotensin-Ⅱ-inducedcardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 andAKT,consequently downregulating nuclear translocation of NF-κB p65.

关键词： FAK-related nonkinase angiotensin Ⅱ cardiomyocyte hypertrophy extracellular signal-regulated kinase 1/2 protein kinase B NF-kappaB p65

Growth-inhibitory Effects of Curcumin on Ovary Cancer Cells and Its Mechanisms

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Journal of huazhong university of science and technology(medical sciences) 2004年第1期24卷 55-58页

作者：郑丽端童强松吴翠环 Department of Pathology Department of Pediatric Surgery

To study the growth inhibitory effects of curcumin on human ovary cancer A2780 cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780 cancer cells, after being treated with 10 μmol/L-50 μmol/L curcumin for 6-24 h, were examined by MTT method. The morphological changes of cancer cells were observed under inversion microscopy. Cellular apoptotic rates were determined by using TUNEL. The protein expression levels of bcl 2, p53 and MDM2 in cancer cells were examined by SP immunohistochemistry. After being treated by various concentrations of curcumin, the growth of cancer cells was inhibited significantly. Some cancer cells presented characteristic morphological changes of apoptosis. The rates of apoptosis were 6.41 % -28.48 % ( P 2 and p53 was decreased, which depended on the action time ( P 2 expression. It was concluded that curcumin could significantly inhibit the growth of ovary cancer cells. The induction of apoptosis by down re gulating the expression of bcl 2 and p53 was probably one of its molecular mechanisms.

关键词： curcumin ovary cancer gene expression apoptosis

Regulating expressions of cyclin D1,pRb,and anti-cancer effects of deguelin on human Burkitt's lymphoma Daudi cells in vitro

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Acta Pharmacologica Sinica 2005年第7期26卷 873-880页

作者： Hong-li L1U Yan CHEN~2 Guo-hui CUI Qiu-ling WU Jing HE Department of Hematology,union hospital,tongji medical college,huazhong university of science arid technology,wuhan 430022,china Department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To investigate anticancer effects and molecular mechanism of deguelin onhuman Burkitt’s lymphoma Daudi cells in vitro and compare the cytotoxicities ofdeguelin on Daudi cells and human peripheral blood monocular cells(PBMC).Methods:The effects of deguelin on the growth of Daudi cells were studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium(MTT)*** dectected through Hoechst 33258 staining and Annexin V/PI *** effect of deguelin on the cell cycle of Daudi cells were studied bya propidium iodide *** expressions of cyclin D 1 and pRb were checkedby Western ***:The proliferation of Daudi cells were decreased indeguelin-treated group with a 24-h IC50value of 51.55 nmol/*** inducedDaudi cells apoptosis was in a time-and dose-dependent manner.G0/G1phaseincreased and S phase decreased in Daudi cells treated with *** deguelin0,5,10,20,and 40 nmol/L treatment for 24 h,G0/G1phase increased from 37.34% to56.56%,whereas S phase decreased from 37.72% to 21.36%.PBMC was lesssensitive to the cytotoxic effect of deguelin than Daudi *** expression ofcyclin D 1 and pRb protein were decreased sharply in Daudi cells treated ***:Deguelin is able to inhibit the proliferation of Daudi cellsby regulating the cell cycle that arrested cells at G0/G1phase and inducing the ***,deguelin selectively induced apoptosis of Daudi cells withlow toxicity in *** antitumor effects of deguelin were related to down-regulating the expression of cyclin D1 and pRb protein.

关键词： deguelin Daudi cells cyclin D1 pRb apoptosis

Intercellular Adhension Molecule-1 in the Pathogenesis of Heroin-induced Acute Lung Injury in Rats

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Journal of huazhong university of science and technology(medical sciences) 2004年第5期24卷 430-432页

作者：周琼白明邹世清 Department of Respiratory Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China Department of Withdrawal Liyuan Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430072 China

The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin into tail vein in rats. Thirty-six rats were randomly divided into heroin-treated groups (1 h, 2 h, 4 h, 6 h and 24 h) and normal control group. Changes in histopathologic morphology and biological markers of ALI were measured. The expression of ICAM-1 in lung tissue was detected by using immunohistochemistry and RT-PCR. The results showed that the W/D ratio and protein contents in BALF of the heroin-treated groups were significantly higher than that of the control group (P<0.01). The histopathological changes in the lung tissue were more obvious in heroin-treated groups. The ICAM-1 protein and mRNA expression in the lung tissue of heroin-treated groups were significantly increased as compared with that of the control group (P<0.01), and correlated with the ALI parameters in a time-dependent manner. Increasing of ICAM-1 expression was involved in the formation of heroin-induced lung injury. Furthermore, the level of expression was positively correlated with the severity of lung injury.

关键词： heroin acute lung injury intercellular adhesion molecule-1

Passive sensitization increases histamine-stimulated calcium signaling and NF-κB transcription activity in bronchial epithelial cells

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Acta Pharmacologica Sinica 2006年第6期27卷 708-714页

作者： Si JIN~(2,5)Dan TIAN~3 Jian-guo CHEN~4 Li-ping ZHU~2 Sheng-yuan LIU~2 Di-xun WANG~2 2 Department of Pathophysiology,tongji medical college,huazhong university of science and technology Key Laboratory of Pulmonary Disease of Ministry of Health of china,wuhan 430030,china 3 Department of Pathology,tongji medical college.huazhong university of science and technology.wuhan 430030,china 4 Department of Pharmacology,tongji medical college,huazhong university of science and technology,wuhan 430030,china Department of Pathophysiology Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Pulmonary Disease of Ministry of Health of china Wuhan China Department of Pathology Tongji Medical College Huazhong University of Science and Technology Wuhan China Department of Pharmacology Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To find out if the two aspects of asthma（chronic airway inflammation andbronchial hyperresponsiveness）are related to hypersensitivity of calcium signal-ing in bronchial epithelial ***:Porcine bronchial epithelial cells（PBEC）were divided into sensitized（S）and nonsesitized（N）*** group S,the cellswere preincubated with serum from ovalbumin sensitized guinea *** group N,the cells were preincubated with serum from nonsensitized guinea *** calcium imaging and ELISA-based NF-κ3 activity were used to evaluate thehistamine-stimulated intracellular free calcium level and NF-κB activity,***:First,0.1μmol/L histamine could induce [Ca2+]ioscillationsin PBEC of group S,but not in group ***,1/Jmol/L histamine could induce[Ca2+]ioscillations of PBEC in both group S and group *** [Ca2+]ioscillationfrequency of PBEC was significantly higher in group S than in group N,thoughthe[Ca2+]ioscillation amplitude showed no difference between the two ***,when 10 μmol/L histamine was used to stimulate PBEC a transient initialincrease followed by a sustained elevation（FSE）of [Ca2+]iwas observed in PBECin both *** amplitude of the FSE of [Ca2+]iin PBEC was significantlyhigher in group S than in group *** subsequent NF-κB activity was in accor-dance to the calcium oscillation frequency evoked by histamine,but not to ***:It was suggested that the increased sensitivity of calciumsignaling in bronchial epithelial cells might contribute to the exorbitant inflamma-tion or increased susceptibility in asthmatic airway epithelial cells.

关键词： asthma histamine calcium signaling bronchi epithelial cell nuclear factor of kappaB

Sonic hedgehog protein promotes bone marrow-derived endothelial pro-genitor cell proliferation,migration and VEGF production via PI 3-kinase/Akt signaling pathways

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Acta Pharmacologica Sinica 2006年第6期27卷 685-693页

作者： Jin-rong FU~2 Wen-li LIU~(2,4)Jian-feng ZHOU~2 Han-ying SUN~2 Hui-zhen XU~2 Li LUO~2 Heng ZHANG~2 Yu-feng ZHOU~3 2 Department of Hematology.tongji hospital,tongji medical college,huazhong university of science and technology,wuhan 430030,china:3 Department of Pediatrics,tongji hospital,tongji medical college,huazhong university of science and technology,wuhan 430030,china Department of Hematology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To investigate the effects of Sonic hedgehog(shh)protein on bone marrow-derived endothelial progenitor cells(BM-EPC)proliferation,migration and vascu-lar endothelial growth factor(VEGF)production,and the potential signaling path-ways involved in these ***:Bone marrow-derived Flk-1~+ cells wereenriched using the MACS system from adult Kunming mice and then BM-EPCwas cultured in gelatin-coated culture *** effects of shh N-terminal pep-tide on BM-EPC proliferation were evaluated using the MTT colorimetric *** migration was assayed using a modified Boyden chamber *** of VEGF was determined by ELISA and immunofluorescence *** potential involvement of PKC and PI3K signaling pathways was exploredusing selective inhibitor or Western ***:The proliferation,migrationand VEGF production in BM-EPC could be promoted by endogenous shh N-terminal peptide at concentrations of 0.1μg/mL to 10 μg/mL,and could be inhib-ited by anti-shh ***-mediated proliferation and migration in BM-EPCcould be partly attenuated by ***-PI3-kinase expression in newlyseparated BM-EPC was low,and it increased significantly when exogenous shhN-terminal peptide was added,but could be attenuated by anti-human/mouse shhN-terminal peptide ***,the inhibitor of the PI3-kinase,but notthe inhibitor of the PKC,significantly inhibited the shh-mediated proliferation,migration and VEGF ***:Shh protein can stimulate bonemarrow-derived BM-EPC proliferation,migration and VEGF production,whichmay promote neovascularization to ischemic *** results also suggeststhat the PI3-kinase/Akt signaling pathways are involved in the angiogenic effectsof shh.

关键词： mouse Sonic hedgehog protein endothelial cells stem cells protein kinase C 1-phosphatidylinositol 3-kinase vascular endothelial growth factor A cell proliferation emigration immigration

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

The Role of Angiopoietin-1 and Thrombospondin-1 in the Kidney of Rats Subject to 5/6 Nephrectomy

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Journal of huazhong university of science and technology(medical sciences) 2009年第5期29卷 557-562页

作者：杨晓刘兰香 Department of Nephrology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

The expression of angiopoietin- 1 （Ang- 1） and thrombospondin- 1 （TSP- 1） in 5/6 subtotal nephrectomy （STN） rats model, and its correlation to the renal microvasculature injury were investigated. Rat 5/6 STN model was established in adult male SD rats, and the sham-operated group and 5/6 STN group were set up. The renal function and histopathological changes were examined at the 1st, 2nd, 4th, 8th and 12th week after operation. The expression orAng-1, TSP-1 and CD31 in renal tissues was detected by using immunohistochemistry. From 2nd to 8th week after operation, Ang-1 was significantly expressed in glomeruli of rats with STN. Ang-1 staining in glomeruli of STN group was increased significantly as compared with that in sham-operated group at 4th and 8th week after operation, and subsequently decreased after the 12th week. The expression of TSP-1 was increased significantly in STN group. As compared with sham-operated group, the CD31 expression was significantly down-regulated from the 2nd week. The expression of Ang-1 mRNA was detected by using RT-PCR at the same time points. The expression of Ang-1 mRNA in renal tissue of rats with STN was significantly up-regulated at the 2nd, 4th and 8th week after operation as compared with that in STN group at other time points or in sham-operated group at the same time points, while decreased evidently at the 12th week as compared with that in sham-operated group. It is concluded that there are changes in the mRNA expression of Ang-1, and the significant up-regulation of the expression of TSP-1 in renal tissue of rats with STN, which may be involved in the remnant renal microvasculature injury.

关键词： 5/6 nephrectomy angiopoietin- 1 thrombospondin- 1 CD31 microvasculature injury

Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity

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Acta Pharmacologica Sinica 2006年第11期27卷 1447-1452页

作者： Chun-yan SUN~1 Yu HU~(1,3)Tao GUO~1 Hua-fang WANG~1 Xiao-ping ZHANG~1 Wen-juan HE~1 Hao TAN~2 1 Institute of Hematology,union hospital,tongji medical college,huazhong university of science and technology.wuhan 430022 2 Institute of Occupational Medicine,School of Public Health,tongji medical college,huazhong Universtiy of science and technology,wuhan 430030,china Institute of Hematology Union Hospital Tongji medical college Huazhong University of Science and Technology Wuhan China Institute of Occupational Medicine School of Public Health Tongji Medical College Huazhong Universtiy of Science and Technology Wuhan China

Aim:To examine the in vitro antitumor activity of resveratrol against multiplemyeloma（MM）cell lines（RPMI 8226,U266,and KM3）,and the ***:The growth inhibition of resveratrol was determined by 3-（4,5-dimethyl-2-thiazyl）-2,5-diphenyl-2H-tetrazolium bromide（MTT）*** of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide *** effect of resveratrol on the invasion throughMatrigel matrix was detected by transwell invasion *** activity ofmatrix metalloproteinase（MMP）-2 and -9 proteins were determined by gelatinzymography *** expression of MMP-2,MMP-9,Bcl-2,Bcl-xL,XIAPand Bax protein were detected using Western blotting ***:Resveratrol inhibited proliferation of MM cells in a dose-and *** of MM cells with resveratrol resulted in apoptotic cell *** down-regulated the expression of the antiapoptotic proteins Bcl-2,Bcl-xLand XIAP and up-regulated the expression of the proapoptotic protein ***,resveratrol inhibited invasion of RPMI 8226,U266,and KM3 cellswith IC50values of 64±8 μmol/L,93±11 μmol/L,and 153±11 μmol/L,*** inhibited the constitutive expression of MMP-2 and-9 proteins ofMM cells and suppressed its gelatinolytic ***:Resveratrol in-hibits the proliferation of MM cells by inducing apoptotic cell *** inhibits MM cell *** inhibition of invasion may be associated withthe attenuation of the enzymatic activities of MMP-2 and-9.

关键词： resveratrol multiple myeloma proliferation invasion matrix metalloproteinase