• 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.

• Archives of Pharmacal Research
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• 제20권3호
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• pp.218-224
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• 1997

Platelet-activating factor (PAF) acetylhydrolase, which removes the acetyl moiety at the sn-2 position, has been found in human amniotic fluid. We purified this enzyme by ammonium sulfate precipitation, and sequential use of DEAE-Sepharose CL-6B, hydroxyapatite, chelating-Sepharose, and Mono Q column chromatographies. This enzyme exhibited broad pH optima and was unaffected by EDTA. Partially purified enzyme had a molecular weight of approximately 34 kDa on SDS-PAGE. In addition, the enzyme activity was inhibited by either diisopropylfluorophosphate(DFP) or p-bromophenacylbromide (p-BPB), suggesting that this enzyme possesses active serine and histidine residues. The enzyme showed similar activity towards PAF and oxidatively modified phosphatidylcholine, but didn't hydrolyze phosphatidylcholine or phosphatidylethanolamine with a long chain fatty acyl group at sn-2 position.

• 대한한방내과학회지
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• 제31권3호
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• pp.500-512
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• 2010

Objectives : This study was designed to investigate the effects of SuJeom-san(SJS) extract in rats with caerulein-induced acute pancreatitis (AP). Methods : We examined changes of pancreatic weight, histological, immunohistochemical and gene expression of cyclooxygenase (COX-2). Thirty-six adult male Sprague-Dawley rats were divided into six groups as follow: normal(Nor), caerulein-induced (Con), caerulein + cefotaxime sodium(CT), caerulein + SJS 3 mg/kg(SJSA), caerulein + SJS 6 mg/kg(SJSB) and caerulein + SJS 12 mg/kg(SJSC) groups. Pancreatic tissues of rats from all groups were removed for histological observation and light, and electron microscopic examination. Platelet activating factor(PAF) and Interleukin-6(IL-6) levels were determined spectrophotometrically. Results : The ratio of pancreas/body weight was significantly(p<0.05) increased in the Con compared with Nor, but significantly(p<0.05) decreased in SJSA, SJSB, SJSC and CT groups compared with Con. Caerulein administration significantly increased(p<0.05) the levels of amylase, but SJSA, SJSB, SJSC and CT significantly(p<0.05) reduced the levels of these enzymes. The levels of platelet activating factor(PAF) increased in Con compared with Nor, but decreased in SJSA, SJSB, SJSC and CT groups compared with Con. Interleukin-6(IL-6) levels increased significantly in all groups compared to Nor at 6 hrs, but significantly(p<0.05) reduced in SJSA, SJSB, SJSC and CT groups compared with Con at 24 hrs. The levels of tumor necrosis factor(TNF)-${\alpha}$ levels increased in all groups compared to Nor at 6 hrs, but significantly(p<0.05) reduced in SJSA, SJSB, SJSC and CT groups compared with Con at 24 hrs. The COX-2 positive materials were observed in the pancreas of the Con, but these positive materials were decreased in the SJS extract treatment group. Conclusion : SJS is potentially capable of limiting pancreatic damage during AP by restoring the fine structure of acinar cells and tissue; therefore, we conclude that SJS may have beneficial effects in the treatment of caerulein-induced AP.

• 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.

• 약학회지
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• 제43권1호
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• pp.117-123
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• 1999

Because of the potent effects of lipid mediators such as prostaglandins (PGs), leukotriens (LTs) and platelet activating factor (PAF) on a variety of cells and tissues, they are considered as major contributors to the process leading to inflammation and allergy. To pursue the mechanism of anti-inflammatory activity of Lonicera japonica, we tested inhibitory effects of 7 flavonoids from Lonicera japonica on arachidonic acid cascade related enzymes, such as inflammatory phospholipase $A_2$, cyclooxygenase-1 and 2, 5-lipoxygenase, in bone marrow derived mast cell (BMMC), and lyso PAF-acetyltransferase in rat spleen microsomes. Anti-inflammatory activities of lonicera japonica are thought to be attributed at least in part to the inhibition of arachidonic acid cascade releated enzymes by flavonoids such as apigenin, luteolin quercetin.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.201-208
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• 1997

It is becoming increasingly clear that the inflammatory reaction can be ascribed to a complex array of mediators generated and released from activated phagocytes. In this study, the effect of PAF on interleukin-1(IL-1) activity by rat alveolar macrophages(AM) was examined using thymocyte proliferation assay in the supernate of sample obtained after 24 hr culture. When AM were cultured with PAF alone, no change in IL-1 activity was observed. However, the combined addition of PAF and muramyl dipeptide(MDP) or lipopolysaccharide(LPS) to AM cultures markedly enhanced IL-1 activity by 2-3 fold compared with AM cultures with the stimulant alone in a concentration dependent fashion. The peack effect was found at $10^{-8}$ M PAF with MDP and $10^{-14}$ M PAF with LPS. the effect of PAF was also tested in silica, toxic respirable dust, -added AM cultures as well as in the cultures containing bacterial compounds. Although silica did not stimulate the IL-1 activity, PAF could enhance IL-1 activity by 2 fold above the value of the silica-treated AM cultures with the peak response at $10^{-12}$ M PAF. Optimal enhancement of IL-1 activity occured when MDP and PAF were present together at the initiation of the 24 hr AM cultures. Additionaly, the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce enhancement of IL-1 activity. When the specific, but structurally different PAF receptor antagonists, BN 52021($10^{-5}$ M) and CV 3988($10^{-5}$ M) was treated 15 min before addition of PAF($10^{-8}$ M) and MDP$(10\;{\mu}g/ml)$ to the AM cultures, it markedly inhibited the enhancement of IL-1 activity induced by PAF. The effects of these PAF antagonists were also observed in LPS$(10\;{\mu}g/ml)$-stimulated cells. Collectively, these data suggest that PAF enhances IL-1 activity by interaction with a specific receptor.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.107-109
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• 1997

For metabolic study of pinusolide, a naturally occurring platelet activating factor antagonist, a synthetic method for preparation of radiolabeled pinusolide was studied. Pinusolide was first oxidized with $OsO_4/NaIO_4 $to 17-nor-8-oxo compound (2), which was subsequently converted to pinusolide by treatment with the Lombardo reagent $(Zn/CH_2Br_2/TiCI_4)$. The Wittily reaction was unsuccessful in the latter carbonyl methylenation of 2.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.241-249
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• 1998

Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$, respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.

• Tuberculosis and Respiratory Diseases
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• 제63권6호
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• pp.497-506
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• 2007

연구배경: 급성호흡곤란증후군의 병인론에 관여하는 PAF의 역할이 다양하고 중요하므로 본 연구에서는 PAF의 또 다른 작용의 가능성, 즉 $cPLA_2$의 활성화(retrograde activation of $cPLA_2$ by PAF)의 가능성을 검사하고자 하였다. 즉, $cPLA_2$의 활성화에 따른 염증성 지질분자의 생성이 산소기의 생성과정을 증폭시키고 이 때 생성된 PAF가 역으로 $cPLA_2$를 활성화시키는지를 확인하기 위하여 본 연구는 고안되었다. 방 법: 흰쥐에서 급성폐손상을 유도하기 위하여 $5{\mu}g$의 PAF를 0.5 ml의 0.25% bovine serum albumin 용액과 혼합한 뒤 기도 내로 직접 분무하거나 0.5 ml의 4.5 mM의 과산화수소를 기도 내로 분무하였다. 대조군의 경우는 0.5 ml의 생리적 식염수를 기도 내로 분무하였다. 5 시간 후에 단백누출지수 측정, 폐장의 MPO 활성도 측정, 폐포 세척액 내의 호중구 산정, CINC 측정, NBT 및 cytochrome-c 환원검사를 시행하였다. 또한 폐장 및 호중구에 서의 $cPLA_2$ 활성도의 측정 및 광학현미경과 전자현미경을 이용하여 형태학적 관찰을 시행하였다. 결 과: PAF투여 후 단백누출지수, MPO, BAL내의 호중 구의 수 및 CINC의 농도가 대조군에 비하여 유의하게 증가하였다. NBT및 cytochrome-c환원검사의 결과 PAF는 호중구의 respiratory burst를 현저히 증가시키고, 분리된 사람의 호중구에서도 산소기의 생성을 현저히 증가시켰 다. 동시에 PAF는 분리된 호중구 및 폐장의 $cPLA_2$의 활성도도 증가 시켰다. 폐장 내로 투여한 과산화수소는 폐장의 $cPLA_2$활성도를 대조군에 비하여 현저히 증가시켰다. 결 론: $cPLA_2$의 활성화에 따라 생성된 PAF는 호중구의 산소기 생성을 증가시켜 폐장 내의 산화성스트레스를 유발하고 동시에 이때 생성된 산화기는 $cPLA_2$를 활성화시키며 PAF 또한 $cPLA_2$의 활성도를 증가시켜 PAF가 급성호흡 곤란증후군의 병인론에 관여하는 것으로 생각된다.

• 동의생리병리학회지
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• 제27권5호
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• pp.644-649
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• 2013

In this study, we aimed to investigate the effect of GamiChungYi-tang(GCY-t) on caerulein-induced acute pancreatitis (AP). It is performed by detecting oxidative stress markers and observing histopathological examination. Thirty adult male rats(Sprague-Dawley) were divided into six groups as follows: normal (NOR,n=5), caerulein-induced (CON,n=5), caerulein+Cefotaxime Sodium(CT,n=5), caerulein+GCY-t (130 mg/kg, CHA,n=5), caerulein+GCY-t (260 mg/kg, CHB,n=5) and caerulein+GCY-t (520 mg/kg, CHC,n=5) groups. Pancreatic tissues of rats from all groups were removed for apoptosis and light, and electron microscopic examination. Blood of rats from all groups were collected for oxidative stress markers inspection and pathological examination. Pancreatic oxidative stress markers were evaluated by the measurements of leukocyte, serum amylase and platelet activating factor (PAF), Interleukin-6 (IL-6) levels were determined spectrophotometrically. CON group has a significant increase (p<0.05) in amylase compared with NOR, but CT and CHA, CHB, CHC groups reduced the levels of these enzyme. The levels of Platelet activating factor (PAF) were increased in CON compared with NOR, but decreased in CT and CHA, CHB, CHC groups compared with CON. Interleukin-6 (IL-6) levels were increased significantly in CON compared with NOR, but reduced in CT and CHA, CHB, CHC groups. In the observations of Optical microscopy and electron microscopy, The experimental groups showed the significant decreases in pancreatic tissue inflammation, edema, vacuolization, necrosis compared to the control group. After all, GCY-t is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue.