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Potential involvement of nitric oxide synthase but not inducible nitric oxide synthase in the development of experimental corneal neovascularization
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作者 Yuan Chen Gao-Qin Liu and Pei-Rong Lu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2011年第4期343-348,共6页
AIM: To investigate the effect of nitric oxide and its synthetase on experimental corneal neovascularization (CRNV). METHODS: CRNV was induced by alkali injury in mice, nitric oxide synthetase (NOS) was inhibited by N... AIM: To investigate the effect of nitric oxide and its synthetase on experimental corneal neovascularization (CRNV). METHODS: CRNV was induced by alkali injury in mice, nitric oxide synthetase (NOS) was inhibited by NG-nitro-L-arginine (L-NAME) and inducible nitric oxide synthetase (iNOS) was inhibited by aminoguanidine hemisulfate salt (AG). The inhibitory effect was detected at day 2 and 4 after corneal alkali injury by reverse transcription polymerase chain reaction (RT-PCR). CRNV was compared between the control and the treated mice by microscopic observation and corneal whole mount CD31 immunostaining. RESULTS: The inhibition of L-NAME to NOS and AG to iNOS after corneal injury was confirmed by RT-PCR (P <0.05). Compared with control mice, L-NAME treated mice exhibited significantly decreased CRNV areas (P<0.05). In contrast, AG treatment failed to attenuate alkali induced CRNV (P>0.05). CONCLUSION: Our findings suggest that NOS but not iNOS plays a critical role in alkali injury induced CRNV. 展开更多
关键词 corneal neovascularization nitric oxide synthase inducible nitric oxide synthase
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Nerve growth factor and inducible nitric oxide synthase expression in the mesencephalon and diencephalon, as well as visual-and auditory-related nervous tissues, in a macaque model of type 2 diabetes 被引量:2
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作者 Qihui Luo Wentao Liu +4 位作者 Jingyao Chen Mingshu Wang Wen Zeng Zhengli Chen Anchun Cheng 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第4期302-307,共6页
The present study detected distribution and expression of nerve growth factor and inducible nitric oxide synthase in the mesencephalon and diencephalon, as well as visual- and auditory-related nervous tissues, in a ma... The present study detected distribution and expression of nerve growth factor and inducible nitric oxide synthase in the mesencephalon and diencephalon, as well as visual- and auditory-related nervous tissues, in a macaque model of type 2 diabetes using immunohistochemistry. Results showed that nerve growth factor expression decreased, but inducible nitric oxide synthase expression increased, in the mesencephalon and diencephalon, as well as visual- and auditory- related nervous tissues. These results suggested that nerve growth factor and inducible nitric oxide synthase play an important role in regulating the development of diabetic visual- and auditory-related diseases. 展开更多
关键词 DIENCEPHALON immunohistochemistry inducible nitric oxide synthase MESENCEPHALON nerve growth factor neural regeneration optic nerve type 2 diabetes
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Biliverdin Reductase-A correlates with inducible nitric oxide synthasein in atorvastatin treated aged canine brain 被引量:2
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作者 Fabio Di Domenico Marzia Perluigi Eugenio Barone 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第21期1925-1937,共13页
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug... Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed following atorvastatin treatment. 展开更多
关键词 neural regeneration age Alzheimer’s disease ATORVASTATIN biliverdin reductase-A cell stress-response cognitive function 4-hydroxy-2-nonenal heme oxygenase-1 inducible nitric oxide synthase oxidative stress neuroregeneration.
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Ginkgo biloba leaf extract effects on inducible nitric oxide synthase, Bcl-2, and Bax expression in rat models of spinal cord injury 被引量:1
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作者 Jiejun Jiao Bin Du 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第8期875-880,共6页
BACKGROUND:Ginkgo biloba leaf extract exhibits neuroprotective effects in spinal cord injury. However, the mechanisms of action remain unclear. OBJECTIVE: To investigate inducible nitric oxide synthase (iNOS) and ... BACKGROUND:Ginkgo biloba leaf extract exhibits neuroprotective effects in spinal cord injury. However, the mechanisms of action remain unclear. OBJECTIVE: To investigate inducible nitric oxide synthase (iNOS) and Bcl-2/Bax expression in the injured spinal cord, and to explore the neuroprotective mechanisms of ginkgo biloba leaf extract in rats with spinal cord injury. DESIGN, TIME AND SETTING: The randomized, controlled, cell molecular biology experiment was performed at Soochow University, China from March 2007 to March 2008. MATERIALS: A total of 120 healthy, adult Sprague Dawley rats were selected for this study. Rat models of moderate acute thoracic (T9) spinal cord injury were established using the modified Allen method. Shuxuening injection was obtained from Zhenbaodao Pharmaceutical Co., Ltd., China. Methylprednisolone was purchased from North China Pharmaceutical Co., Ltd. METHODS: All rats were equally and randomly divided into four groups. Only the spinal cord was exposed in the sham operation group rats. In the trauma group, rats were not treated with drugs following spinal cord injury. Rats in the hormone group were intraperitoneally injected with 30 mg/kg methylprednisolone following spinal cord injury. Rats in the ginkgo biloba leaf extract group were intraperitoneally infused with a 1.0 mL/kg Shuxuening injection per day. MAIN OUTCOME MEASURES: At 1 hour, as well as 1, 3, 5, 7, and 14 days after spinal cord injury, iNOS- and Bcl-2/Bax-positive cells were quantified with immunohistochemistry. Pathological changes were detected using hematoxylineosin staining under an optical microscope. RESULTS: Spinal cord injury in the ginkgo biloba leaf extract and hormone groups was milder compared with the trauma group. Demyelination was significantly ameliorated and the necrotic cavity was obviously reduced in the injured spinal cord of rats in the ginkgo biloba leaf extract and hormone groups at each time point. iNOS expression was increased in the injured spinal cord, and reached a peak at 5 days. The number of iNOS-positive cells was lower in the ginkgo biloba leaf extract and hormone groups compared with the trauma group (P 〈 0.05-0.01). The number of iNOS-positive cells was lower in the ginkgo biloba leaf extract group compared with the hormone group at 7 and 14 days after spinal cord injury (P 〈 0.05). Bcl-2 expression reached a peak at 3 days, and Bax expression reached a peak at 5 days following rat spinal cord injury. Bcl-2 expression was increased, but Bax expression was decreased in the ginkgo biloba leaf extract and hormone groups compared with the trauma group (P 〈 0.05-0.01). Bcl-2 expression was greater, but Bax expression was reduced in the ginkgo biloba leaf extract group compared with the hormone group at 7 and 14 days after spinal cord injury (P 〈 0.05). CONCLUSION: Ginkgo biloba leaf extract exhibits neuroprotective effects by upregulating Bcl-2 expression, downregulating Bax expression, and significantly inhibiting high expressions of iNOS in the injured spinal cord. The neuroprotective effects of ginkgo biloba leaf extract are greater compared with methylprednisolone at 1 week after spinal cord injury. 展开更多
关键词 apoptosis BCL-2/BAX ginkgo biloba leaf extract inducible nitric oxide synthase METHYLPREDNISOLONE NEUROPROTECTION spinal cord injury
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EFFECT OF TNF-a AND IFN-g ON THE EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE GENE AND PROLIFERATION INHIBITION OF HUMAN COLON CANCER CELL LINE 被引量:1
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作者 厐希宁 王芸庆 宋今丹 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2002年第2期131-136,共6页
Objective: To study the expression of the inducible nitric oxide synthase (iNOS) gene and the effects of tumor necrosis factor-α(TNF-a) and interferon-γ(IFN-g)on proliferation of the continuous cultured human colon ... Objective: To study the expression of the inducible nitric oxide synthase (iNOS) gene and the effects of tumor necrosis factor-α(TNF-a) and interferon-γ(IFN-g)on proliferation of the continuous cultured human colon cancer cell line CCL229. Methods: Using the molecular and biochemical techniques and electron microscopy to analyze the expression of iNOS, production of NO and growth characteristics of human colon cancer cells. Results: cytokine treatment can induce expression of the iNOS gene and production of nitric oxide was significantly higher after treatment of CCL229 cells with TNF-αor IFN-γ. Treatment with either cytokine or a combination of both significantly increased levels of Malondialdehyde (MDA) over control. Furthermore, cytokine treatment increased the proliferation inhibition rate as assessed in vitro and decreased the cell proliferation index on flow cytometry. Electron microscopy showed that cells treated with cytokines had fewer pseudopodia or cell processes than control cells and that cytokine treated cells had dilatation of the mitochondria and endoplasmic reticulum and dilated vesicular or tubular cisternae. Conclusion: Our findings indicate that TNF-α and IFN-γ induce the expression of iNOS gene in CCL229 cells, which increases the production of nitric oxide, inhibits proliferation, causes lipid peroxidation, and results in ultrastructural changes. 展开更多
关键词 inducible nitric oxide synthase Gene expression Colon cancer cells Proliferation inhibition
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Clinical Significance of a Myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary Syndrome 被引量:1
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作者 王燕颖 王文多 +2 位作者 张艳霞 赵欣 杨东亮 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第4期437-442,共6页
The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects we... The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO–463 G/A genotype and its relationship with iNOS expression in a typical cell block from ascitic fluid were detected by immunohistochemistry and polymerase chain reaction-restricted fragment length polymorphism analysis (PCR-RFLP). In the HPS group, the partial pressure of oxygen in blood and ascitic fluid was significantly decreased (8.95±1.58 kPa and 6.81±0.95 kPa, respectively; both P<0.01), while the partial pressure of carbon dioxide significantly increased (4.62±0.20 kPa and 5.92±0.45 kPa, respectively; P<0.01). MPO and iNOS levels were significantly increased in the HPS group as compared with the non-HPS group. These increases were even more remarkable in ascitic fluid (41.36±11.62 and 13.23±4.81 μg/L; 10.27± 3.20 and 4.95±1.12 μg/L) than in blood (16.66±5.24 and 4.87±1.73 μg/L; 5.79±2.31 and 2.35±0.84 μg/L). The distribution of the MPO genotypes GG, GA, and AA were 76.2%, 22.2% and 1.6% in the HPS group, and 57.7%, 37.9% and 4.4% in the non-HPS group (P<0.05). The expression of iNOS was significantly higher in patients with the G alleles (G/G and G/A) (61.54%, 48/78) than in patients with A alleles (G/A and A/A) (38.46%, 30/78) (P<0.01). It was suggested that the expression levels of iNOS and MPO were correlated with HPS-induced hypoxemia. The MPO-463 G/A mutation might be a protective factor that prevents the development of HPS. The MPO might be involved in the regulation of iNOS expression. In humans, MPO pathways, the iNOS/NO system, and their interaction might have an impact on the occurrence and development of HPS. 展开更多
关键词 hepatopulmonary syndrome MYELOPEROXIDASE inducible nitric oxide synthase POLYMORPHISM
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Expression and role of inducible nitric oxide synthase in ischemia-reperfusion liver in rats 被引量:1
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作者 Li-Ming Wang Xiao-Feng Tian +3 位作者 Qian-Ying Song Zhen-Ming Gao Fu-Wen Luo Chun-Ming Yang From the Department of General Surgery and Organ Transplantation Center, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2003年第2期568-574,共7页
OBJECTIVE: To investigate the expression and the role of iNOS expression in hepatic ischemia-reperfusion (L/R) injury. METHODS: Male Wistar rats were subjected to 30-minute hepatic ischemia, then iNOS protein and iNOS... OBJECTIVE: To investigate the expression and the role of iNOS expression in hepatic ischemia-reperfusion (L/R) injury. METHODS: Male Wistar rats were subjected to 30-minute hepatic ischemia, then iNOS protein and iNOS mRNA expression in liver tissue was assessed by Western blot and RT-PCR analysis respectively at different time points after reperfusion. The effects of L-NAME (Nω-nitro-L-arginine methyl ester, a nonselective NOS inhibitor) or AE-ITU (aminoethytl-isothiourea, a relative selective inhibitor of iNOS) treatment were also evaluated. RESULTS: High levels of iNOS protein and mRNA expression were detected in the liver tissue subjected to I/R, but not in the sham-operated rats. iNOS protein and iNOS mRNA expression reached a maximum on the first day after reperfusion and decreased later. The levels of iNOS protein and iNOS mRNA disappeared on 7th, 3rd day after reperfusion respectively. The high iNOS expression was correlated with hepatic dysfunction. L-NAME administration worsened hepatic dysfunction induced by hepatic I/R. In contrast, AE-ITU administration showed mild protective effects against hepatic dysfunction induced by hepatic I/R. CONCLUSION: Ischemia-reperfusion may induce or up-regulate the expression of iNOS protein and iNOS mRNA, which is detrimental to hepatic I/R injury. 展开更多
关键词 inducible nitric oxide synthase ischemia-reperfusion injury LIVER
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Lanthanum Chloride Inhibiting Expression of Inducible Nitric Oxide Synthase in RAW264.7 Macrophages Induced by Lipopolysaccharide
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作者 郭菲 娄远蕾 +2 位作者 汪泱 谢安 李国辉 《Journal of Rare Earths》 SCIE EI CAS CSCD 2007年第3期359-363,共5页
Nitric oxide(NO)and its reaction products were key players in the pathophysiology of sepsis and shock.The present study was designed to explore the effects of lanthanum chloride(LaCl3)on inducible nitric oxide syn... Nitric oxide(NO)and its reaction products were key players in the pathophysiology of sepsis and shock.The present study was designed to explore the effects of lanthanum chloride(LaCl3)on inducible nitric oxide synthase(iNOS)expression,at both gene and protein levels,in RAW264.7 macrophages induced by Lipopolysaccharide(LPS).Reverse transcription polymerase chain reaction(RT-PCR),immunofluorescence,and western blot were employed to measure iNOS gene expression,localization,and protein expression respectively.NO production in culture supernatants was detected by the nitrate reductase method.The results showed that LaCl3 significantly attenuated the iNOS gene and protein expression,as well as NO production in RAW264.7cells induced by LPS. 展开更多
关键词 lanthanum chloride LIPOPOLYSACCHARIDE nitric oxide inducible nitric oxide synthase rare earths
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Spatio-temporal expression of inducible nitric oxide synthase in and surrounding a region of rat frontal lobe damaged with a sharp instrument
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作者 Zhixian He Zhijun Zhang +3 位作者 Yulin Dong Guangming Lü Ting Wang Hengjian Ni 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第2期123-128,共6页
BACKGROUND: Inducible nitric oxide synthase (iNOS) cannot be detected in the neurons and glial cells of normal rats, but iNOS can be found in some neurons and glial cells of rats following ischemic, traumatic, neur... BACKGROUND: Inducible nitric oxide synthase (iNOS) cannot be detected in the neurons and glial cells of normal rats, but iNOS can be found in some neurons and glial cells of rats following ischemic, traumatic, neurotoxic or inflammatory damage. OBJECTIVE: To investigate iNOS expression and iNOS-positive cell types at various time points following damage to the rat frontal lobe using a sharp instrument. DESIGN: A nerve molecular biology, randomized, controlled study. TIME AND SETTING: This experiment was performed at the Department of Human Anatomy, Institute of Neurobiology, Medical School of Nantong University, between April 2006 and December 2007. MATERIALS: Rabbit anti-iNOS antibody (Santa Cruz, USA), biotin labeled goat anti-rabbit antibody (Sigma, USA), reverse transcription kit (Biouniquer, Hong Kong, China) and horseradish peroxidase labeled goat anti-rabbit antibody (Pierce, USA) were used for this study. METHODS: A total of 112 healthy rats aged 3 months were randomly assigned into a sham operation group (n = 28) and a damage group (n = 84). Rat models of frontal lobe damage were induced in the damage group using a sharp instrument to make an incision in the frontal lobe cortex. In the sham operation group, the rat bone window was opened but brain tissues were left intact. MAIN OUTCOME MEASURES: Parameters were measured at 3, 6, 12, 24, 72, 120 and 168 hours following damage in both groups. Pathological changes were observed using Nissl staining and hematoxylin-eosin staining. Expression of iNOS mRNA, iNOS protein and iNOS-positive cells were examined by RT-PCR, Western blot analysis and immunohistochemistry, respectively. RESULTS: A large number of inflammatory cells infiltrated the damaged region 12 and 24 hours following damage, iNOS mRNA and iNOS protein expression increased in and around the damaged region 3 hours following damage, reached a peak at 24 hours, and then gradually decreased. The changes in iNOS-positive cell number reflected the changes in iNOS mRNA and iNOS protein expression after damage, iNOS was mainly found in neural cells at 3 and 6 hours, in macrophages at 12 and 24 hours, and in glial cells at 72 and 120 hours after damage. iNOS-positive cells were few in and surrounding the damaged region at 168 hours. There were a few iNOS-positive neural cells in the rat frontal lobe cortex in the sham operation group. CONCLUSION: Neurons, macrophages and glial cells can express iNOS following rat frontal lobe damage caused by a sharp instrument. The levels of iNOS expression, and the cell types expressing iNOS, change with time. 展开更多
关键词 frontal lobe damage inducible nitric oxide synthase RT-PCR WESTERN-BLOT IMMUNOHISTOCHEMISTRY rats
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Spatiotemporal expression of inducible nitric oxide synthase and cyclooxygenase 2 in the spinal cord during early stage sciatic nerve crush injury
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作者 Qiben Wang Linfeng Zheng +4 位作者 Yinggui Xie Qinghong Huang He Huang Zhicheng Zeng Song Wu 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第10期747-751,共5页
BACKGROUND: Previous studies have shown that inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) participate in inflammatory immune responses and neuropathic pain following peripheral nerve injury... BACKGROUND: Previous studies have shown that inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) participate in inflammatory immune responses and neuropathic pain following peripheral nerve injury. However, few reports have addressed time-dependent expression of iNOS and COX-2 following peripheral nerve injury. OBJECTIVE: To investigate spatiotemporal expression of iNOS and COX-2 during early stage sciatic nerve crush injury.DESIGN, TIME AND SETTING: The randomized, controlled, animal experiment was performed at the Laboratory of Applied Anatomy, Department of Human Anatomy and Neurobiology, Central South University, China from September 2006 to September 2007.MATERIALS: Mouse anti-rat iNOS monoclonal antibody and goat anti-rat COX-2 monoclonal antibody (Transduction Laboratory, USA), as well as biotinylated rabbit anti-mouse lgG and biotinylated rabbit anti-goat IgG (Santa Cruz Biotechnology, USA) were used in the present study.METHODS: A total of 48 healthy, adult, Sprague Dawley rats were randomly assigned to three groups. In the model group (n = 32), crush injury to the right sciatic nerve was established using an artery clamp. The model group was further assigned to four subgroups according to survival time (6,12, 24, and 72 hours), respectively (n = 8). Sham surgery (n = 8) and normal control (n = 8) groups were also established.MAIN OUTCOME MEASURES: iNOS and COX-2 expression was detected in the L4-6 spinal cord with immunohistochemistry. Gray values of iNOS- and COX-2-postive cells in the anterior horn and posterior horn of spinal cord, as well as quantification of iNOS- and COX-2-positive cells in the anterior horn of spinal cord, were measured.RESULTS: iNOS and COX-2 expression gradually increased in the anterior horn and posterior horn of the spinal cord on the damaged side over time from 6 hours following sciatic nerve injury (P〈0.05) and peaked at 72 hours. Simultaneously, the number of iNOS- and COX-2-positive cells similarly increased in the anterior horn of spinal cord on the damaged side (P〈 0.05).CONCLUSION: iNOS and COX-2 expression increased in the spinal cord during early stage sciatic nerve crush, which suggested that iNOS and COX-2 participate in occurrence and development of inflammatory immune responses following peripheral nerve injury. 展开更多
关键词 inducible nitric oxide synthase cyclooxygenase 2 sciatic nerve spinal cord peripheral nerve injury neural regeneration
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Cervical sympathetic trunk transection affects inducible nitric oxide synthase expression in rat hippocampus following focal cerebral ischemia/reperfusion injury
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作者 Liangzhi Xiong Yan Wang +1 位作者 Qingxiu Wang Qingshan Zhou 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第10期1084-1087,共4页
BACKGROUND: The stellate ganglion block (SGB) plays a protective role in focal cerebral ischemia/reperfusion injury. The human SGB can be simulated by transection of the cervical sympathetic trunk (TCST) in rats.... BACKGROUND: The stellate ganglion block (SGB) plays a protective role in focal cerebral ischemia/reperfusion injury. The human SGB can be simulated by transection of the cervical sympathetic trunk (TCST) in rats. OBJECTIVE: To observe the effects of TCST on inducible nitric oxide synthase (iNOS) levels and cerebral infarct volume in the hippocampus of rats with cerebral ischemia/reperfusion injury, and to analyze the mechanism of action. DESIGN, TIME AND SETTING: A completely randomized, controlled, neuropathological experiment was performed at the Institute of Neurological Disease, Taihe Hospital, Yunyang Medical College between March and September 2006. MATERIALS: A total of 93 Wistar rats, aged 1718 weeks, of either gender, were used for this study. 2, 3, 5-triphenyl tetrazolium chloride was purchased from Changsha Hongyuan Biological Reagent Company China. Rabbit iNOS antibody and goat anti-rabbit IgG antibody were the products of Wuhan Boster Biological Reagent Co., Ltd., China. METHODS: Ten rats were randomly selected for the sham-operated group. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion (MCAO) using the suture method in the remaining rats. Forty successful rat models were randomly and equally divided into the following two groups: (1) TCST group: subsequent to TCST, MCAO was performed for 2 hours, followed by 24 hours reperfusion; (2) model group: rats underwent experimental procedures similar to the TCST group, with the exception of TCST. Rats in the sham-operated group were subjected to experimental procedures similar to the model group; however, the thread was only introduced to a depth of 10 mm. MAIN OUTCOME MEASURES: Following 24 hours of reperfusion, functional neurological deficits were scored. Brain tissue sections from ten rats of each group were used to measure cerebral infarct volume by TTC staining. Hippocampal tissue sections of an additional ten rats from each group were used to detect iNOS levels using the streptavidin-peroxidase immunohistocbemistry method. Experimental data were expressed as absorbance values. RESULTS: Of the 93 selected rats, 50 were included in the final analysis. After MCAO for 2 hours, followed by 24 hours reperfusion, the absorbance values of iNOS-immunoreactive product were significantly greater in the model group compared to the TCST and sham-operated groups (P 〈 0.05). However, there was no difference between the TCST and sham-operated groups (P 〉 0.05). In addition, cerebral infarct volume in the model group was significantly greater compared to the TCST group (P 〈 0.05). The TCST group performed with lower total functional neurological scores compared to the model group (P 〈 0.05). CONCLUSION: TCST protects the brain against focal cerebral ischemia/reperfusion injury by possibly down-regulating hippocampal iNOS expression. 展开更多
关键词 BRAIN ISCHEMIA/REPERFUSION inducible nitric oxide synthase sympathetic trunk
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Effects of Baicalin on Expression of Inducible Nitric Oxide Synthase in Cultured Fibroblasts Stimulated by Cytokines
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作者 毕新岭 顾军 +3 位作者 聂本勇 李泉 刘辉 米庆胜 《Chinese Journal of Integrated Traditional and Western Medicine》 2004年第1期40-43,共4页
Objective: To investigate the effects of baicalin on expression of inducible nitric oxide syn-thase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulate... Objective: To investigate the effects of baicalin on expression of inducible nitric oxide syn-thase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulated with tumor necrosis factor-α (TNF-α), interferon-γ(IFN-γ), interleukin-8 (IL-8) in different groups. iNOS was detected by western blot and immunocytochemistry assay, and in addition, the effects of baicalin on its expression were investigated. Results: Fibroblasts did not express iNOS without cytokine stimulation. When treated for 24 h with 1.0×106 U/LTNF-α, 0.2×106U/L IFN-γ, 0.2×106 pg/L IL-8 alone or in combinations indicated, fibroblasts produced iNOS when stimulated by TNF-α alone while neither IFN-γ nor IL-8 could induce the production of iNOS. The combination of TNF-α and IL-8 induced a strong expression of iNOS, the combined exposure of three kinds of cytokines showed an even stronger effects. The strongly stained area was in the cytoplasm near the nuclei. Expression of iNOS induced by TNF-α and IL-8 was inhibited by 50μg/ ml of baicalin. Conclusion: Fibroblasts might express iNOS when stimulated by certain cytokines. Baicalin decreased production of nitric oxide through inhibiting the expression of iNOS, furthermore it reduced inflammation, which might be part of its mechanisms in treating psoriasis. 展开更多
关键词 BAICALIN FIBROBLASTS inducible nitric oxide synthase
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Dynamic changes of inducible nitric oxide synthase expression in rat's retina and its role on blood-retinal barrier injury after acute high intraocular pressure
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作者 Min Li Ju-Fang Huang +5 位作者 Yi Li Jing Shen Lu-Jia Yang Qian Chen Quan-Peng Zhang Xi-Nan Yi 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2022年第7期1053-1061,共9页
AIM: To clarify the role of inducible nitric oxide synthase(i NOS) in blood-retinal barrier(BRB) injury after acute high intraocular pressure(IOP) in rats.METHODS: Forty-two Sprague-Dawley(SD) rats were randomized int... AIM: To clarify the role of inducible nitric oxide synthase(i NOS) in blood-retinal barrier(BRB) injury after acute high intraocular pressure(IOP) in rats.METHODS: Forty-two Sprague-Dawley(SD) rats were randomized into 7 groups [control(Cont), 3, 6, 12, 24, 48, and 72 h, n=6]. Except Cont group, other groups’ retina tissue was obtained at corresponding time points after a model of acute high IOP have been established in rats. The expression of i NOS and tight junction protein zonula occludens(ZO)-1 was detected by Western blotting. Evans blue(EB;3%) was injected into the great saphenous vein to detect the leakage of EB by spectrophotometer. Nine rats were divided into Cont, 6 h, 12 h groups, the expression of i NOS was localized by immunofluorescence. In order to verify the role of i NOS in the damage to BRB, thirty-six rats were randomly divided into 4 groups [Cont, Cont+inhibitor(Inh), 6 h and 6 h+Inh, n=9]. After treatment with the i NOSspecific inhibitor 1400 W, the expression of i NOS and ZO-1 and the leakage of BRB were detected again.RESULTS: The immunofluorescence results showed that the expression of i NOS was observed in the Cont group and 6 h group, but not in the 12 h group. i NOS was mainly expressed in the retinal nerve fiber layer, ganglion cell layer and inner nuclear layer and that it did not colocalize with the retinal ganglion cell marker Neu N but was co-expressed with the vascular endothelial cell marker CD31. Western blotting showed that in the early period(3 h, 6 h) after acute high IOP, the expression of i NOS was upregulated, then the down-regulation of i NOS were tested in the follow-up timing spots. ZO-1 expression showed a continuous downregulation after 6 h. The quantitative results for EB showed that the amount of EB leakage began to increase at 3 h after acute high IOP. At 6 h, the leakage of EB was lower, but at 12 h, the leakage of EB was highest, after which it gradually recovered but remained higher than that in the Cont group. The expression of i NOS was down-regulated after 1400 W treatment. ZO-1 expression was not significantly changed in the Cont+Inh group and the 6 h group, and significantly down-regulated in the 6 h+Inh group, and the leakage of EB was significantly increased after 1400 W treatment.CONCLUSION: These results suggest that the upregulation of i NOS expression in the early stage after acute high IOP may have a protective effect on BRB injury. 展开更多
关键词 inducible nitric oxide synthase acute high intraocular pressure blood-retinal barrier ZO-1
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Research Progress on Inducible Nitric Oxide Synthase in the Pathogenesis of Pancreatic Malignancy
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作者 Huimin Xiong Ruiyao Wang Chao Zhang 《Proceedings of Anticancer Research》 2021年第4期27-29,共3页
Pancreatic cancer is a common tumor of the digestive system.At present,the pathogenesis is still unclear,but current research on inducible nitric oxide synthase in relation to the pathogenesis of pancreatic malignant ... Pancreatic cancer is a common tumor of the digestive system.At present,the pathogenesis is still unclear,but current research on inducible nitric oxide synthase in relation to the pathogenesis of pancreatic malignant tumors is particularly extensive.Therefore,this article focuses on the research progress on inducible nitric oxide synthase in the pathogenesis of pancreatic cancer. 展开更多
关键词 inducible nitric oxide synthase Pancreatic cancer Research progress
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AB029.The role of inducible nitric oxide synthase in deleterious effects of Kinin B1 receptor in diabetic retinopathy
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作者 Rahmeh Othman Elvire Vaucher Réjean Couture 《Annals of Eye Science》 2018年第1期435-435,共1页
Background:Overexpression of inducible nitric oxide synthase(iNOS)has been reported in diabetic retinopathy(DR).The kinin B1 receptor(B1R)is also overexpressed in DR,and can stimulate iNOS via Gαi/ERK/MAPK pathway.We... Background:Overexpression of inducible nitric oxide synthase(iNOS)has been reported in diabetic retinopathy(DR).The kinin B1 receptor(B1R)is also overexpressed in DR,and can stimulate iNOS via Gαi/ERK/MAPK pathway.We previously showed that the topical administration of a B1R antagonist,LF22-0542,significantly reduces leukocyte infiltration,increased vascular permeability and overexpression of several inflammatory mediators,including iNOS in DR.Thus,the aim of this study was to determine whether the pro-inflammatory effects of B1R are attributed to oxidative stress caused by the activation of iNOS pathway in order to identify new therapeutic targets for the treatment of DR.iNOS and B1R being absent in the normal retina,their inhibition is unlikely to result in undesirable side effects.The approach will be no invasive by eye application of drops.Methods:Diabetes was induced in male Wistar rats(200-230 g)by a single intraperitoneal injection of streptozotocin(STZ,65 mg/kg b.w).One week later,rats were randomly divided into four groups(N=5)and treated for one week as follows:Gr 1:control rats treated with the selective iNOS inhibitor(1,400 W,0.06μM twice a day by eye-drops×7 days),Gr 2,STZ-diabetic rats treated with 1,400 W,Gr 3:control rats received a selective B1R agonist[Sar(D-Phe8)-des-Arg9-BK,100μg twice a week]by intravitreal injections(itrv)and treated with 1,400 W,Gr 4:STZ-diabetic rats+B1R agonist+1,400 W.At the end of treatment and two weeks post-STZ,three series of experiments were carried out to measure vascular permeability(by Evans blue dye method)and the expression of vasoactive and inflammatory mediators,including iNOS,VEGF-A,VEGF-R2,IL-1β,Cox-2,TNF-α,bradykinin 1 and 2 receptors and carboxypeptidase M/kininase 1(by Western Blotting and qRT-PCR).The nitrosative stress(nitrosylation of proteins)was also assessed by Western Blotting.One-way Anova test with Bonferroni post hoc was used for statistical analysis.Results:STZ-diabetic rats showed a significant increase in retinal vascular permeability(22.8μg/g Evans blue dye per g of fresh retinas,P=0.016)compared with control rats and control treated rats(17.2 and 16.8μg/g respectively).The injections of B1R agonist amplified the increase of vascular permeability which was normalized by the 1,400 W.The overexpression of inflammatory markers was also normalized by the 1,400 W in STZ-diabetic rats received or not the B1R agonist.Conclusions:These results support a contribution of iNOS in the deleterious effects of B1R in this model of diabetic retinopathy.Hence,iNOS inhibition by ocular application of 1,400 W may represent a promising and non-invasive therapeutic approach in the treatment of diabetic retinopathy. 展开更多
关键词 Rétinopathie diabétique inducible nitric oxide synthase(iNOS) B1 receptor(B1R)
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A Review on the Research Progress of Inducible Nitric Oxide Synthase in the Pathogenesis of Pancreatic Malignancy
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作者 Huimin Xiong Ruiyao Wang Chao Zhang 《Journal of Clinical and Nursing Research》 2021年第4期151-153,共3页
Pancreatic cancer is a common tumor of the digestive system,at present,the pathogenesis is still unclear,but in the current research on the pathogenesis of pancreatic malignant tumors,the research on inducible nitric ... Pancreatic cancer is a common tumor of the digestive system,at present,the pathogenesis is still unclear,but in the current research on the pathogenesis of pancreatic malignant tumors,the research on inducible nitric oxide synthase is particularly extensive.Therefore,this article focuses on the research progress of inducible nitric oxide synthase in the pathogenesis of pancreatic cancer.This is a review. 展开更多
关键词 inducible nitric oxide synthase Pancreatic cancer Research progress
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Expression of Apoptosis and Inducible Nitric Oxide Synthase in Trophoblastic Cells in Early Spontaneous Abortion 被引量:1
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作者 夏革清 孙永玉 《Journal of Reproduction and Contraception》 CAS 2001年第1期56-60,共5页
Objective To investigate the effect of apoptosis and inducible nitric oxide (iNOS) on the early spontaneous abortion Methods TUNEL method was used to detect the apoptosis in trophoblast cells in early pregnancy wi... Objective To investigate the effect of apoptosis and inducible nitric oxide (iNOS) on the early spontaneous abortion Methods TUNEL method was used to detect the apoptosis in trophoblast cells in early pregnancy with and without spontaneous abortion (the experiment group and the control group), while iNOS was detected by both in situ hybridization and immunohistochemistry. By computer color magic image analysis system(CMIAS), positive cell indexes were represented by D (density) and N/S(number/square) in both apoptosis and in situ hybridization, in immunohistochemistry were N/S and PU(positive unit). Results Positive cell indexes of apoptosis D and N/S were significntly higher in the experiment group (0.48±0.004, 0.045±0.002) than that in the control group(0.35+0.06, 0.031±0.003. P<0.001). D and N/S of inducible nitric oxide synthase in situ hybridization were 0.33±0.028, 0.074±0.001 respectively in the experiment group and 0.13±0.015, 0.019±0.004 respectively in the control group. N/S and PU were significantly higher in the experiment group(0.058±0.007, 11.94±2.01) than that in the control group (0.007±0.001, 1.18±0.35, P<0.01). There existed a positive correlation between iNOS and apoptosis too. Conclution Apoptosis and iNOS in trophoblasts might play an important role in early spontaneous abortion and there was a positive correlation between apoptosis and iNOS. 展开更多
关键词 spontaneous abortion APOPTOSIS inducible nitric oxide
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Effects of Nephritis No.3 Recipe on Nitric Oxide,Nitric Oxide Synthase Secreted by Cultured Mesangial Cells in Rats and the Gene Expression of Inducible Nitric Oxide Synthase
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作者 陈志强 黄怀鹏 +2 位作者 黄文政 朱小棣 林清棋 《Chinese Journal of Integrated Traditional and Western Medicine》 2003年第3期210-214,共5页
Objective:To explore the effect of the Nephritis No. 3 (N-3) recipe on nitric oxide (NO), nitric oxide synthase (NOS) secreted by cultured mesangial cells (MC) and its gene expression of the in-ducible nitric oxide sy... Objective:To explore the effect of the Nephritis No. 3 (N-3) recipe on nitric oxide (NO), nitric oxide synthase (NOS) secreted by cultured mesangial cells (MC) and its gene expression of the in-ducible nitric oxide synthase (iNOS). Methods:The drug (nephritis No. 3)-containing serum was prepared with serum pharmacological technique, and then was applied to react on mesangial cells cultured in fetal calf serum (FCS) and cells cultured in FCS plus lipopolysaccharide. To observe the secretion of NO and NOS and the gene expression of iNOS by means of RT-PCR. Results:Under the two kinds of culture conditions, the content of NO and NOS in the groups with drug-containing serum were higher than those without drug-containing serum (P<0. 05, P<0. 01), and the expression of iNOS mRNA was up-regulated too. Conclusion: The N-3 could significantly promote the secretion of NO and NOS and the mRNA expression of iNOS in rats. 展开更多
关键词 Nephritis No. 3 recipe mesangial cell nitric oxide nitric oxide synthase
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Expression of inducible nitric oxide synthase in human gastric cancer 被引量:5
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作者 Jun Y Fei G +1 位作者 Ebert MP Malfertheiner P 《World Journal of Gastroenterology》 SCIE CAS CSCD 1999年第5期430-431,共2页
关键词 STOMACH NEOPLASMS nitric oxide synthase nitric oxide
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Expressions of inducible nitric oxide synthase and matrix metalloproteinase-9 and their effects on angiogenesis and progression of hepatocellular carcinoma 被引量:31
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作者 Min-Hua Sun Xi-Chun Han Ming-Ku Jia Wei-Dong Jiang Min Wang Hong Zhang Gang Han Yi Jiang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第38期5931-5937,共7页
AIM: To determine the expressions of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 (MMP-9)in hepatocellular carcinoma (HCC) and to investigate the relationship between iNOS and MMP-9 expression... AIM: To determine the expressions of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 (MMP-9)in hepatocellular carcinoma (HCC) and to investigate the relationship between iNOS and MMP-9 expression and their effects on angiogenesis and progression of HCC.METHODS: Tn this study, we examined iNOS, MMP-9,and CD34 expression in specimens surgically removed from 32 HCC patients and 7 normal liver tissues by immunohistochemical staining. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34-positive cells.RESULTS: The positive rates of iNOS and MMP-9expression were 71.88% (23/32) and 78.13% (25/32) in HCC. MMP-g expression was significantly correlated with tumor size, capsule status, TNM stage, and risk of HCC recurrence (P= 0.032, P= 0.033, P= 0.007, and P= 0.001,respectively). There was also a significant relationship between iNOS expression and capsule status and risk of HCC recurrence (P = 0.04g and P = 0.004, respectively),but no correlation between iNOS expression and tumor size and TNM stage. There was a positive association between MVD and TNM stage and risk of HCC recurrence (P = 0.037 and P = 0.000, respectively). The count of MVD was significantly different in different iNOS and MMP-9 immunoreactivity groups (F= 17.713 and 17.097, P = 0.000 and P = 0.000, respectively). The examination of Spearman's rank correlation coefficient showed that there was a significant positive correlation between MVD and iNOS,MMP-9 immunoreactivity (r= 0.754 and 0.751, P= 0.000 and P=0.000, respectively). There was also a significant association between MMP-9 and iNOS expression in HCC (P = 0.010).CONCLUSION: Nitric oxide (NO) produced by iNOS could modulate MMP-9 production and therefore contribute to tumor cell angiogenesis and invasion and metastasis in HCC. The strong expression of iNOS and MMP-9 in HCC may be helpful in evaluating the recurrence of HCC,predicting poor prognosis. For patients with strong expression of MMP-9 and iNOS, the optimal treatment scheme needs to be selected. 展开更多
关键词 一氧化氮 金属蛋白酶-9 基因表达 肝细胞癌
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