• Journal of Chest Surgery
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• 제35권5호
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• pp.343-349
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• 2002

배경: 흰쥐의 기도에 과산화수소를 분무함으로서 급성 염증성 반응을 일으켜 phospholipase $A_2$(PLA$_2$)와 endogenous oxidative stress에 산소기가 어떤 영항을 미치는지에 대해 알아보고자 하였다. 대상 및 방법: 호중구에 의해 유리된 산소기가 phospholipase $A_2$를 다시 활성화시킨다는 가설을 증명하기위해 phospholipase $A_2$의 활성도와 lysoplatelet activating factor acetyltransferase(lysoPAF AT)를 수산화수소 분무 5시간 후에 측정하였다. 또한, PLA$_2$활성화에 따른 나쁜 영향에 대해 알아보기 위하여 폐 질량/체중의 비, bronchoalveolar lavage(BAL)내의 단백 함량을 측정하였다. 폐장 내의 염증반응은 호중구의 폐장내 침윤에 따른 respiratory burst에 의한 oxidative stress가 그 원인일 것으로 추정되므로 BAL 내의 호중구 수와 myeloperoxidase(MPO)수치를 측정하였다. 또한 oxidative stress에 의한 영향을 화인하기 위하여 형태학적, 조직화학적 검사도 시행하였다. 결과: 과산화수소를 투여하고 5시간 뒤에 폐장은 심한 호중구의 침윤 및 폐 질량의 증가를 볼 수 있었다. BAL 내의 단백 함량은 정상폐의 경우에서보다 훨씬 증가된 것을 볼 수 있었다. PLA$_2$의 활성도 또한 증가되어 있었다. 흥미롭게도, 과산화수소를 투여한 폐에서 lysoPAF AT 활성도의 증가를 측정함으로서 platelet activating factor(PAF) 생성의 증가를 확인할 수 있었다. 형태학적으로, 광학현미경상 폐장의 무기폐 및 염증세포의 침윤을 관찰할 수 있었다. 이것은 PLA$_2$의 활성화에 따라 생성된 염증성 지질 분자에 의해 초래된 결과라고 생각되어진다. Cerium chloride 세포화학 전자 현미경상 많은 양치 cerrous perhydroxide의 침윤을 관찰할 수 있었다. 반면 정상 폐장에서는 전혀 관찰되어지지 않았다. 결론: 이상의 모든 결과들은 호중구에 의한 oxidative stress에 의한 폐장의 손상과 일치하므로 산소기에 의해 생성된 PLA$_2$가 내인성 oxidative stess에 관여한다고 볼 수 있다.

• Clinical and Experimental Reproductive Medicine
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• 제18권2호
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• pp.133-142
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• 1991

본 연구의 목적은 임신 초기 자궁 조직중의 cyclic nucleotide 의 변화 및 PAF 가 이들에 미치는 영향을 관찰함으로써 PAF 가 흰쥐의 초기 임신에 어떻게 관련하는지를 조사하기 위함이다. 시험구로써 임신 각 일에 $1{\mu}g$ 의 PAF 혹은 이것의 수용체 길항제인 1.25mg의 BN-52021이 근육내 조사되었고 비 임신구 및 대조구에 대하여는 PBS만이 주사되었다. 자궁 조직중의 cAMP 및 cGMP 농도는 분석용 test kit를 사용하여 분석되었다. 비 임신구 경우 자궁 조직중 cAMP 농도는 단백질 mg 당 $2.91{\pm}0.33$ pmol로서 임신 보다도 낮았고 cGMP 농도 또한 $0.39{\pm}0.20$ pmol로서 임신구보다 낮은 경향이 었다. 자궁 조직중 cAMP 의 최고농도는 임신 3일째 ($5.92{\pm}1.72$ pmol/mg protein) 였고 cGMP 경우는 임신 4일째($1.03{\pm}0.22$ pmol/mg protein) 이었다. 임신 각일에 PAF 는 PAF 처리하지 아니한 대조구에 비하여 증가된 cAMP 를 보여주었으나(임신 0, 2, 그리고 4 일째 경우 p<0.05) BN-52021은 감소된 경향을 나타내었다. cGMP에 대하여는 PAF나 BN-52021 공히 일정한 효과적 경향을 보이지 아니하였다. 따라서, 임신은 자궁 조직중 cyclic nucleotide에 영향을 미칠 수 있으며 흰쥐의 착상기동안 PAF는 cGMP에 대하여 보다는 cAMP에 영향을 미침으로써 착상에 관련된 일련의 반응에 영향을 미칠 것으로 사료된다.

• 대한약리학회지
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• 제29권1호
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• pp.107-120
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• 1993

입자 또는 용해성 자극 물질들은 칼슘 이동의 변화와 protein kinase C의 활성화를 초래하여 식 세포의 반응을 자극하는 것으로 추정하고 있다. 이에 비해서 protein kinase C가 활성화되면 호중구에서 agonist에 의한 세포 칼슘 농도의 증가가 억제된다고 보고하고 있다. PAF는 peritoneal macrophage에서 세포내 칼슘 농도를 용량에 따라 증가시켰으며 칼슘의 유출이 동반되었다. PAF에 의한 세포내 칼슘 농도의 증가는 TMB-8, verapamil과 TTX의 영향을 받지 않았다. TEA는 PAF에 의한 세포내 칼슘 이동을 자극하였으며 세포내 칼슘 농도의 감소를 지연시켰다. 5mM EGTA는 거의 완전히 PAF에 의한 세포내 칼슘 이동을 억제하였다. PAF의 첨가 후에 세포막 투과성은 반응 5분까지 현저하게 증가하였으며 이후 느리게 증가하였다. PAF에 의한 LDH 유리는 EGTA와 TMB-8에 의하여 약간 감소하였다. PAF에 의하여 자극된 superoxide 생성은 EGTA, TMB-8과 verapamil에 의하여 억제되었으나 TTX와 TEA의 영향은 받지 않았다. PAF에 의한 세포내 칼슘 농도의 증가, 세포막 투과성의 증가와 superoxide 생성은 IQSP, chlorpromazine과 propranolol에 의하여 억제되었다. PAF에 의한 LDH 유리는 chlorpromazine에 의하여 유의하게 그리고 propranolol에 의하여 다소 적게 억제되었다. PMA 전처리 후에 macrophage에서 세포내 칼슘 농도의 상승과 LDH 유리에 대한 PAF의 자극 효과는 유의하게 감소되었다. 이상의 결과로 부터 PAF는 세포내 칼슘 농도를 증가시키고 protein kinase C를 활성화시킴에 의하여 마우스 peritoneal macrophage에 자극 작용을 나타낼 것으로 시사된다. Protein kinase C를 미리 활성화시키면 macrophage 반응에 대한 PAF의 자극 작용은 억제될 것으로 추정된다.

• Clinical and Experimental Reproductive Medicine
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• 제23권1호
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• pp.1-6
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• 1996

There are a number of problems during the process of culture in vitro on fertilization and embryo development compared to those on in vivo counterparts. And the platelet activating factor (PAF), which is found not only in mammalian spermatozoa but also preembryos, is implicated on reproductive process. To improve the environment of culture on in vitro fertilization and embryo development, coculture using salpingeal epithelial cells has been considered to accept the better result on pregnancy rate. This study was designed to determine if two different culture systems, coculture alone and PAF treated coculture, are positive or negative influence on process of in vitro fertilization and embryo culture in mouse. The cell cleavage rate reached to 2-4 cell stage at 24 hours of culture is 56.81% (50/88) and 48.21%(54/112) respectively, in PAF treated group which is added PAF on coculture and in coculture group. But the rate of cells cleavage was similar in both group after 48 hours of culture. The rate of unfertilization after insemination of oocytes was higher in coculture group(55..53%) than in PAF treated group(42.37%). And in assessment of undeveped embryos, the rate of equalized cell block was similar on both, coculture alone (35.3%)and PAF treated coculture(35.5%). while unequalized cell block was higher rate in PAF treated coculture(19.4%) than coculture alone (11.8%). But the rate of cytoplasmic degeneration of undeveloped embryos was significantly higher in PAF treated coculture than coculture alone. In conclusion, we have observed that PAF treated coculture is superior in the rates of in vitro fertilization and early embryo cell cleavage compared to those in coculture alone, but there is no difference on the rates of embryo develpments, cell degeneration, cell quality in both PAF treated coculture and coculture alone when the embryo cells were continuosly cultured for 48 hours or more.

• The Korean Journal of Physiology and Pharmacology
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• 제15권4호
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• pp.203-210
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• 2011

Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cAMP levels and activates protein kinase A, thereby inhibiting vascular smooth muscle cell (VSMC) proliferation. We investigated whether AMP-activated protein kinase (AMPK) activation induced by heme oxygenase-1 (HO-1) is a mediator of the beneficial effects of cilostazol and whether cilostazol may prevent cell proliferation and reactive oxygen species (ROS) production by activating AMPK in VSMC. In the present study, we investigated VSMC with various concentrations of cilostazol. Treatment with cilostazol increased HO-1 expression and phosphorylation of AMPK in a dose- and time-dependent manner. Cilostazol also significantly decreased platelet-derived growth factor (PDGF)-induced VSMC proliferation and ROS production by activating AMPK induced by HO-1. Pharmacological and genetic inhibition of HO-1 and AMPK blocked the cilostazol-induced inhibition of cell proliferation and ROS production.These data suggest that cilostazol-induced HO-1 expression and AMPK activation might attenuate PDGF-induced VSMC proliferation and ROS production.

• 동의생리병리학회지
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• 제18권3호
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• pp.857-862
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• 2004

The purpose of this research was to investigate the effects of supercritical fluid extract of Kamichungbieum (SFE) on allergic reaction. SFE (500 mg/kg) inhibited the systemic anaphylaxis induced by compound 48/80 or platelet activating factor and inhibited the passive cutaneous anaphylaxis (PCA) induced by anti-dinitrophenyl (DNP)-lgE and DNP-human serum albumin (HSA) in vivo. Also, SFE inhibited the SRSC-induced delayed type hypersensitivity and inhibited the hind paw edema induced by histamine. In addition, SFE inhibited the permeability of evans blue induced by acetic acid and inhibited the writhing syndrome induced by acetic acid. These results indicate that SFE may be useful for the prevention and treatment of allergy related disease.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.665-672
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• 1997

This study aimed to investigate the mechanism of cerebroprotection of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rat. Right middle cerebral artery(MCA) of Sprague-Dawley rat was occluded for 2 hours using an intraluminal filament technique. After 22 hours of reperfusion, morphometrically detectable infarct was developed in the cortex and striatum identical to the territory of MCA. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, as well as an inducible nitric oxide synthase(iNOS) inhibitor aminoguanidine(1 mg/kg, i.p., respectively) administered 5 min after MCA occlusion. PAF antagonists significantly inhibited the enzymatic activities of both myeloperoxidase and iNOS in the cerebral hemisphere ipsilateral to ischemia, whereas aminoguanidine did not inhibit myeloperoxidase activity but significantly inhibited the iNOS activity. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through inhibition of leukocyte infiltration and iNOS activity in the postischemic brain.

• 한방안이비인후피부과학회지
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• 제12권1호
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• pp.113-142
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• 1999

The purpose of this research was to investigate the effect of Kamidangkwieumja(KDEJ) water extract on the allergy reaction in mice. The results were obtained as follows: 1. The passive cutaneous anaphylaxis induced by egg albumin in fat was not affected. 2. The lethal anaphylaxis induced by platelet activating factor in mice. was inhibited. 3. The degranulation of peritoneal mast cells induced by compound 48/80 was not affected. 4. The acute hind paw edema was inhibited after 2hours later when it was induced by histamine. 5. The permeability of evans blue into peritoneal cavity induced by acetic acid was not affected. 6. Arthus reaction in mice was not affected. 7. The delayed type hypersensitivity induced by SRBC was inhibited. 8. The contact dermatitis induced by DNFB was not affected. 9. The hemagglutination titer induced by SRBC was inhibited. 10. The writhing syndrome induced by acetic acid was inhibited. 11. The population of heper T cells in mice thymus was enhanced. 12. The phagocytic activity of peritoneal macrophages was enhanced. 13. The production of nitric oxide from peritoneal macrophages was not affected. These results suggest that the anti-allergy effect of KDEJ is caused by steroidlike and enhanced immune action. The steroidlike action of KDEJ correspond with steroid-applying-method that frequently used in clinic, so it is used io treatment of psoriasis. The research on anti-allergy of KDEJ might has to be continued.

• Toxicological Research
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• 제12권1호
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• pp.137-141
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• 1996

A teratological study was performed using New Zealand White rabbits to examine the teratological potential of Ginkgo biloba extract(EGb 761), which is a known strong platelet activating factor antagonist. Ginkgo biloba extract(EGb 761) was administered per intravenously during the organogenesis period (day 6th to 18th of gestation) of rabbits at dose levels of 7.5, 15, and 30 mg/kg/day. All pregnant females were sacrificed on day 29 of gestation and teratological abnormalities of their fetuses was examined. No statistically significant difference of body weight change between control and treated groups during experimental periods was noted. There was no statistically signifiant difference of numbers of corpus lutes and implantations, fetal death ratio, fetal sex ratio, and placental weight between control and rabbits exposed to three different concentration ranges of Ginkgo biloba extract (EGb 761). No marked external, visceral and skeletal abnormalities related to Ginkgo biloba extract(EGb 761) were observed in the fetuses. In conclusion Ginkgo biloba extract(EGb 761) does not show any effect on implantation or embryonic development.

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.111-121
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• 1996

Antiulcer effects of Artemisia herba extract (DA-9601) were evaluated in various types of experimental gastric ulcer induced in rats. And the effects of DA-9601 on mucus, basal and stimulated gastric acid secretion were also investigated in rats. DA-9601 (12.5∼400 mg/kg, p.o.) prevented the formation of gastric ulcers induced by 60% EtOH in 150 mM HC1, restraint water immersion stress, platelet activating factor (PAF), aspirin in 150 mM HCI with Pylorus-ligation and indomethacin. DA-9601 (4∼400 mg/kg, p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer and significantly stimulated mucus secretion in a dose-dependent manner. DA-9601 (20∼200 mg/kg, i.d.), however, did not inhibit basal gastric acid secretion in pylorus ligated rats and DA-9601 (200 mg/kg, i.d.) failed to influence histamine-, pentagastrin- and carbachol- stimulated gastric acid secretion. These results suggest that DA-9601 has inhibitory action on gastric lesion and ulceration through increasing mucus secretion in the stomach of rats without influencing basal and stimulated gastric acid secretion.