郑凌
糖尿病及其并发症的机理和治疗;器官缺血再灌注损伤的机理和治疗。
个性化签名
- 姓名:郑凌
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
细胞生物学
- 研究兴趣:糖尿病及其并发症的机理和治疗;器官缺血再灌注损伤的机理和治疗。
郑凌,教授、博士生导师
专业: 细胞生物学
研究方向:糖尿病及其并发症的机理和治疗;器官缺血再灌注损伤的机理和治疗
学 历:
1992-1996,武汉大学生物系, 学士
1996-1999,华南农业大学植物细胞分子生物学,硕士
2000-2005,美国凯西西储大学Case Western Reserve University,药理系,博士
主要工作经历与任职:
2008-现在,教授,武汉大学生命科学学院。
2007-2008, 讲师,凯西西储大学Case Western Reserve University,医学系
2005-2007,博士后,凯西西储大学Case Western Reserve University,医学系
目前的主要研究领域和兴趣:
1)研究糖尿病及其并发症糖尿病视网膜病变(Diabetic Retinopathy), 糖尿病肾病 (Diabetic Nephropathy) ,神经疾病(Diabetic Neuropathy) 的机理,病变过程,及治疗。
2) 研究器官缺血再灌注(Ischemia and reperfusion)的机理,病变过程,及治疗。
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201
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成果数
7
郑凌, Ling Zheng, , *, Shuqing Liu, Ming-Zhong Sun, Jinsook Chang, Mark R. Chance, and Timothy S. Kern
Proteomics. 2009 April; 9 (7): 1869-1882.,-0001,():
-1年11月30日
Retinal ischemia contributes to multiple ocular diseases while aminoguanidine (AMG) treatment significantly inhibits the neuronal and vascular degeneration due to acute retinal ischemia and reperfusion (I/R) injury. In the present study, two-dimensional differential in gel electrophoresis (2D DIGE) was applied to profile global protein expression changes due to retinal I/R injury, and the protection effects mediated by AMG. Retinal ischemia was induced by elevated intraocular pressure to 80–90 mmHg for 2 hours, and reperfusion was established afterward. Retinal tissues were collected 2 days after I/R injury. After 2D DIGE analysis, a total of 96 proteins were identified. Among them, 28 proteins were identified within gel spots whose intensities were normalized by AMG pre-treatment, pathway analysis indicated that most were involved in glycolysis and carbohydrate metabolism. Selected enzymes identified by MS/MS within these pathways, including transketolase, triosephosphate isomerase 1, aldolase C, total enolase, and pyruvate kinase were validated by quantitative Western blots. Glycolytic enzymes and other differentially regulated proteins likely play previously unrecognized roles in retinal degeneration after I/R injury, and inhibition of the resulting metabolic changes, using pharmacologically gents such as AMG, serve to inhibit the changes in metabolism and mitigate retinal degeneration. Select glycolytic enzymes may provide novel therapeutic targets for inhibiting the neuronal and vascular degeneration after retinal I/R injury.
2D DIGE, Aminoguanidine, Glycolysis, Protein profiling, Retinal ischemia and reperfusion
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【期刊论文】CD40 Mediates Retinal Inflammation and Neurovascular Degeneration1
郑凌, Jose-Andres C. Portillo, * Jennifer Van Grol, *† Ling Zheng, ‡ Genevieve Okenka, * Katrin Gentil, * Alejandra Garland, * Eric C. Carlson, * Timothy S. Kern, *‡§ and Carlos S. Subauste*†‡
The Journal of Immunology,2008, 181: 8719-8726.,-0001,():
-1年11月30日
Retinopathies are major causes of visual impairment. We used a model of ischemic retinopathy to examine the role of CD40 in the pathogenesis of retinal injury. Retinal inflammation, loss of ganglion cells, and capillary degeneration were markedly attenuated in ischemic retinas of CD40/ mice. Up-regulation of NOS2 and COX2 after retinal ischemia were blunted in CD40/mice. NOS2-COX-2 up-regulation in ischemic retinas from wild-type mice was at least in part explained by recruitment of NOS2 COX-2 leukocytes. Up-regulation of KC/CXCL1 and ICAM-1 also required CD40. Retinal endothelial and Muller cells expressed CD40. Stimulation of these cells through CD40 caused ICAM-1 up-regulation and KC/CXCL1 production. Bone marrow transplant experiments revealed that leukocyte infiltration, ganglion cell loss, and up-regulation of proinflammatory molecules after retinal ischemia were dependent on CD40 expression in the retina and not peripheral blood leukocytes. These studies identified CD40 as a regulator of retinal inflammation and neurovascular degeneration. They support a model in which CD40 stimulation of endothelial and Muller cells triggers adhesion molecule up-regulation and chemokine production, promoting the recruitment of leukocytes that express NOS2/COX-2, molecules linked to neurovascular degeneration.
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郑凌, Timothy S. Kern, Casey M. Miller, , Yunpeng Du, Ling Zheng, Susanne Mohr, Sherry L. Ball, M. Kim, Jeffrey A. Jamison, and David P. Bingaman
DIABETES, VOL. 56, FEBRUARY 2007,-0001,():
-1年11月30日
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郑凌, L. Zheng & Y. Du & C. Miller & R. A. Gubitosi-Klug & T. S. Kern & S. Ball & B. A. Berkowitz
Diabetologia (2007) 50: 1987-1996,-0001,():
-1年11月30日
Aims/hypothesis Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos−/−). Materials and methods iNos−/− mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls. Mice were killed at different time points after the induction of diabetes for assessment of vascular histopathology, cell loss in the ganglion cell layer (GCL), retinal thickness, and biochemical and physiological abnormalities. Results The concentrations of nitric oxide, nitration of proteins, poly(ADP-ribose) (PAR)-modified proteins, endothelial nitric oxide synthase, prostaglandin E2, superoxide and leucostasis were significantly (p<0.05) increased in retinas of WT mice diabetic for 2 months compared with nondiabetic WT mice. All of these abnormalities except PARmodified proteins in retinas were inhibited (p<0.05) in diabetic iNos−/− mice. The number of acellular capillaries and pericyte ghosts was significantly increased in retinas from WT mice diabetic for 9 months compared with nondiabetic WT controls, these increases being significantly inhibited in diabetic iNos−/− mice (p<0.05 for all). Retinas from WT diabetic mice were significantly thinner than those from their non-diabetic controls, whereas diabetic iNos−/− mice were protected from this abnormality. We found no evidence of cell loss in the GCL of diabetic WTor iNos−/− mice. Deletion of iNos had no beneficial effect on diabetes-induced abnormalities on the electroretinogram. Conclusions/interpretation We demonstrate that the inflammatory enzyme iNOS plays an important role in the pathogenesis of vascular lesions characteristic of the early stages of diabetic retinopathy in mice.
Capillary degeneration, Diabetic retinopathy, Inducible nitric oxide synthase, Inflammation, itric oxide, PAR activation
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【期刊论文】Salicylate-Based Anti-Inflammatory Drugs Inhibit the Early Lesion of Diabetic Retinopathy
郑凌, Ling Zheng, Scott J. Howell, Denise A. Hatala, Kun Huang, and Timothy S. Kern,
DIABETES, VOL. 56, FEBRUARY 2007,-0001,():
-1年11月30日
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【期刊论文】Retinal Ischemia and Reperfusion Causes Capillary Degeneration: Similarities to Diabetes
郑凌, Ling Zheng, , * Bendi Gong, Denise A. Hatala, and Timothy S. Kern, *
Investigative Ophthalmology & Visual Science, January 2007, Vol. 48, No.1,-0001,():
-1年11月30日
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郑凌, Ling Zheng, Csaba Szabo´, and Timothy S. Kern,
DIABETES, VOL. 53, NOVEMBER 2004,-0001,():
-1年11月30日
The current study investigated the role of poly(ADPribose) polymerase (PARP) in the development of diabetic retinopathy. Activity of PARP was increased in whole retina and in endothelial cells and pericytes of diabetic rats. Administration of PJ-34 (a potent PARP inhibitor) for 9 months to diabetic rats significantly inhibited the diabetes-induced death of retinal microvascular cells and the development of early lesions of diabetic retinopathy, including acellular capillaries and pericyte ghosts. To further investigate how PARP activation leads to cell death in diabetes, we investigated the possibility that PARP acts as a coactivator of nuclear factor- B (NF- B) in the retinal cells. In bovine retinal endothelial cells (BRECs), PARP interacted directly with both subunits of NF- B (p50 and p65). More PARP was complexed to the p50 subunit in elevated glucose concentration (25 mmol/l) than at 5 mmol/l glucose. PJ-34 blocked the hyperglycemia-induced increase in NF- B activation in BRECs. PJ-34 also inhibited diabetes-induced increase expression ofintercellular adhesion molecule-1, a product of NF-B-dependent transcription in retina, and ubsequent leukostasis. Inhibition of PARP or NF- B inhibited the hyperglycemia (25 mmol/l glucose)-induced cell death in retinal endothelial cells. Thus, PARP activation plays an important role in the diabetes-induced death of retinal capillary cells, at least in part via its regulation of NF-B. Diabetes 53: 2960-2967, 2004
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