• Journal of Acupuncture Research
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• v.23 no.3
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• pp.215-229
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• 2006

목적 : 당귀는 전통적으로 학습과 기억능력 증진 및 각종 질병치료에 우수한 효과가 있는 것으로 알려져있다. 본 연구에서는 이러한 인삼약침이 소음스트레스가 유발된 태아쥐의 해마 및 시상하부에서 nitric oxide synthase에 미치는 영향을 관찰하였다. 방법 : 당귀약침이 소음스트레스에 미치는 영향을 연구하기 위하여 태아기에 소음스트레스를 유발하고 생후 4주후 7일간 당귀약침을 투여한 후 NADPH-d 조직화학법을 시행하였다. 결과 : 1. 소음스트레스는 태아쥐의 해마 및 시상하부에서 NOS 발현이 유의하게 증가하였다. 2. 당귀약침은 해마 CAI에서만 소음스트레스에 의해서 증가된 NOS 발현을 유의하게 억제하였다. 3. 당귀약침은 시상하부 PVN, DMH 및 LHA에서 소음스트레스에 의해서 증가된 NOS 발현을 유의하게 억제하였다. 결론 : 본 연구를 통하여 당귀약침이 소음스트레스가 유발된 태아쥐의 해마 및 시상하부에서 증가된 NOS 발현을 유의하게 억제시켜 태아의 스트레스 자극에 당귀약침치료가 유의한 효과가 있음을 확인하였다.

• Korean Journal of Acupuncture
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• v.23 no.4
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• pp.157-167
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• 2006

목적 : 인삼은 전통적으로 학습과 기억능력 증진 및 각종 질병치료에 우수한 효과가 있는 것으로 알려져 있다. 본 연구에서는 이러한 인삼약침이 소음스트레스가 유발된 태아쥐의 해마 및 시상하부에서 nitric oxide synthase에 미치는 영향을 관찰하였다. 방법 : 인삼약침이 소음스트레스에 미치는 영향을 연구하기 위하여 태아기에 소음스트레스를 유발하고 생후 4주 후 7일간 인삼약침을 투여한 후 NADPH-d 조직화학법을 시행하였다. 결과 : 소음스트레스는 태아쥐의 해마 및 시상하부에서 NOS 발현이 유의하게 증가하였다. 2. 인삼약침은 해마 CA1에서만 소음스트레스에 의해서 증가된 NOS 발현을 유의하게 억제하였다 3. 인삼약침은 시상 하부 PVN, DMH 및 LHA에서 소음스트레스에 의해서 증가된 NOS 발현을 유의하게 억제하였다. 결론 : 본 연구를 통하여 인삼약침이 소음스트레스가 유발된 태아쥐의 해마 및 시상하부에서 증가된 NOS 발현을 유의하게 억제시켜 태아의 스트레스 자극에 인삼약침치료가 유의한 효과가 있음을 확인하였다.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.420-433
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• 1996

Background : There have been many debates about the effects of nitric oxide on the neurogenic inflammation. The role of nitric oxide in the neurogenic inflammation of airways will be required a better understanding of the localization and types of nitirc oxide synthase(NOS) activity in the neurogenic inflammation of airways. Method : To investigate the role of nitric oxide in airway neurogenic inflammation, 1) the effects of neurokinin receptor antagonist (FK224) and nitric oxide synthase inhibitor, $N^{\omega}$-nitro-L-arginine (L-NNA) on plasma extravastion were evaluated in four groups of Sprague-Dawley rats ; sham operation group(sham NANC group), electrical vagal stimulation group(NANC2 group), intravenous pretreatment groups with FK224 (1mg/kg ; FK224 group), and L-NNA(1mg/kg ; L-NNA group) 15 minutes before vagal NANC stimulation. 2) NOS activity in trachea with neurogenic inflammation was localized by immunohistochemical stain. Immunohistochemical stain was performed by antibodies specific for inflammatory cells(iNOS), brain(bNOS), and endothelium (eNOS) on trachea obtained from sham NANC, NANC2, and FK224 groups. Results : The results are that plasma extravsation in neurogenic inflammation of rat airways was inhibited by FK224, but enhanced by L-NNA pretreatment(P<0.05). There was significantly increased infiltration of inflammatory cells in subepithelium of neurogenic inflammatory trachea, but the reduction of subepithelial infiltration of inflammatory cells was observed after pretreatment with FK224(P<0.05). Immunostaining with anti-iNOS antibody showed strong reactivity only in infiltrated inflammatory cells in neurogenic rat trachea, and these iNOS reactivity was reduced by pretreatment with FK224. bNOS immunoreactivity was significantly increased only in the nerves both of neurogenic inflammatory and FK224 pretreated trachea compared with sham NANC trachea(p<0.05). eNOS immunoreactivity was not significant change in endothelium in neurogenic inflammation of rat trachea. Conclusion : These results suggest that nitric oxide released from iNOS in infiltrated inflammatory cells has main role in neurogenic inflammation of rat trachea. The presence of bNOS immunoreactivity in the nerves indicates that nitric oxide may be released from the nerves in rat trachea with neurogenic inflammation.

• Korean Journal of Pharmacognosy
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• v.41 no.1
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• pp.14-20
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• 2010

In this study, we investigated the anti-inflammatory effects of fupenjic acid (FA) isolated from the Potentilla discolor in both RAW 264.7 and mouse primary peritoneal macrophage cells. FA pretreatment significantly inhibited nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ productions in the lipopolysaccharide (LPS)-induced RAW 264.7 and mouse primary peritoneal macrophage cells. Consistent with these observations, Western blot and RT-PCR analyses revealed that FA inhibited the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels. In addition, FA reduced the release of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). These results suggest that the down regulation of iNOS and COX-2 expression and TNF-$\alpha$ and IL-6 production by fupenjic acid are responsible for its anti-inflammatory effects.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.155-161
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• 2001

Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.71-77
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• 2010

Purpose: To determine whether upregulation of inducible nitric oxide synthase (iNOS) transcription and translation is related to radicular pain in a model of lumbar disc herniation. Also, to investigate the temporal changes of mRNA expression of iNOS and the identity of iNOS and transient receptor potential vanilloid (TRPV) 1 channel expression cells in dorsal root ganglion (DRG) of a model of lumbar disc herniation. Methods: A lumbar disc herniated rat model was developed by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the DRG. Rats were tested for mechanical allodynia of the plantar surface of both hind paws 2 days before surgery and 1, 5, 10, 20 and 30 days postoperatively. Reverse transcription polymerase chain reaction (RT-PCR) was used to follow iNOS mRNA expression. To stain iNOS and TRPV1 in DRG, an immunohistochemical study was done 10 days after surgery. Results: A significant drop in mechanical withdrawal threshold on the ipsilateral and contralateral hind paws was observed 1 day after surgery and was prolonged to 30 days in rats with lumbar disc herniation. The expression of mRNA for iNOS peaked at postoperative day 10 on both sides of the DRG. iNOS-positive sensory neurons in the DRG varied in size from large to small diameter cells. A majority of small and intermediate sensory neurons were TRPV1-positive cells. Double immunofluorescence staining for TRPV1 and iNOS revealed that most intermediate TRPV1-positive sensory neurons co-localized with iNOS-positive neurons. Conclusion: Nucleus pulposus-induced mechanical allodynia can be generated without mechanical compression. This pain is related to temporal changes in expression of iNOS mRNA in the DRG. Co-localization of TRPV1 and iNOS in intermediate neurons of the DRG is correlated with pain modality and intensity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.785-791
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• 2005

Corydalis Tuber has traditionally been used for the treatment of water retention in the body. Administration of the aqueous extract of Corydalis Tuber has been known to be effective for the control of pain and treatment of arthritis. It was reported that Corydalis Tuber possesses anti-inflammatory activity and modulates the intestinal immune system. The effect of Corydalis Tuber against LPS-stimulated expressions of COX-2, iNOS, and $IL-1{\beta}$ in cells of the murine RAW 264.7 macrophages was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), $PGE_2$ immunoassay, and NO detection. The aqueous extract of Corydalis Tuber was shown to suppress $PGE_2$ production by inhibition on the LPS-stimulated enhancement of COX-2 enzyme activity, $IL-1{\beta}$, and iNOS expression in the RAW 264.7 macrophages. Present results suggest that Corydalis Tuber exerts anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ expressions, resulting in inhibition of $PGE_2$ synthesis. Corydalis Tuber has anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ mRNA expressions, resulting in inhibition of $PGE_2$ and NO synthesis.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.147-154
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• 2005

Objective: In this study, the effects of Liriope Platyphylla against LPS-induced inflammation was investigated. Methods: Cell viability was determined using the MTT assay. To identify expressions of COX-2 and iNOS mRNA, RT-PCR was performed. Assessment of PGE2 synthesis was performed using the PGE2 immunoassay. Measurement of NO synthesis was performed using the NO detection. Result : The MTT assay revealed that Liriope Platyphylla exerted no significant cytotoxicity in the microglial BV2 cells. RT-PCR analysis revealed that the mRNA levels of COX-2 and iNOS were significantly decreased in the LPS- and 5 mg/ml Liriope Platyphylla treated group. From the PGE2 immunoassay and NO detection, PGE2 and NO synthesis was significantly suppressed in the LPS- and 5 mg/ml Liriope Platyphylla treated group. Conclusion : In these study, Liriope Platyphylla was shown to suppress PGE2 and NO production by inhibiting LPS-stimulated enhancement of COX-2 enzyme activity and iNOS expression. It is very possible that Liriope Platyphylla can offer a valuable mode of therapy for the treatment of brain inflammatory diseases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.1
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• pp.36-41
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• 2006

Objective. The objective of this study was to examine the hypothesis that inflammatory synovial fluid from TMJ internal derangement initiates a transient increase in intracellular calcium concentration ([$Ca^{2+}$]i) in chondrocytes and the induced Ca2+ signaling affects iNOS/COX-2 gene expression patterns following exposure to inflamed synovial fluid. Materials and Methods. Two female adult patients with symptoms of TMD who agreed to participate in the study were selected for this study. Immortalized human juvenile costal chondrocyte C-28/I2 was grown to 80% confluency and synovial fluids from two patients were added respectively to culture media for 24 hours at the concentration of 100ng/10ml. Confocal laser scanning microscope (CLSM) was used to examine changes of intracellular calcium concentration ([$Ca^{2+}$]i). RT-PCR was performed to identify the expression profile of IL-1${\alpha}$, iNOS, COX-2. Results. Increased [$Ca^{2+}$]i was observed in chondrocytes subjected to inflamed synovial fluid compared to control cultures and in respective cultures exposed to inflamed synovial fluids from each patient, IL-1${\beta}$, COX-2 mRNA were detected. However, in neither case iNOS mRNA was expressed. IL-1${\alpha}$, COX-2, and iNOS mRNA were expressed in control culture. Conclusion. Our results show that immortalized chondrocytes cultured with inflamed synovial fluids from patients diagnosed as disc displacement without reduction and limitation in mouth opening showed increased calcium concentration and expression of COX-2 while inhibiting the production of iNOS, which in turn could adversely affect the chondrocytes in at least short term by hindering physiologic role of NO against inflammatory cascades. These findings suggest that inflamed synovial fluid may differentially regulate the transcriptomes of relevant inflammatory mediators, especially iNOS/COX-2 axis in chondrocytes through adjusting calcium transients.

• Journal of Yeungnam Medical Science
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• v.13 no.2
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• pp.159-172
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• 1996

대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.