Oxidized phospholipids and lipoprotein-associated phospholipase A_2 as important determinants of Lp(a) functionality and pathophysiological role

Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.

Phospholipase A_2 and Its Relationship with Acute Lung Injury in Acute Pancreatitis in Dogs

Acute fulminant pancreatitis was produced in dogs by injection of autobile into the main pancreatic duct.After injection the phospholipase A_2(PLA_2)activities in serum,lung lymph and bronchoalveolar lavage fluid(BAL)were elevated significantly,lung lymph flow and pulmonary transvascular potein clearance increased progressively,protein content and cell numbers in BAL in the experimental animals were significantly higher than those in the control animals.Furthermore the lung index,wet to dry lung weight ratio,extravascular lung water to bloodless dry lung weight ra- tio,extravascuar lung water to bloodless dry lung weight ratio increased significantly as compared to control animals.Pretreatment with PLA_2 inhibitor,chloroquine,blocked the changes mentioned above.This experiment suggests:1.PLA_2 activity in lung lymph fluid as well as in serum and BAL is elevated in acute hemorrhagic pancreatitis.2.Elevated PLA_2 activity may increase the pulmonary vascular permeability.3.PLA_2 is the major factor leading to pulmonary edema in acute hemorrhagic pancreatitis.4.Phagocytes contribute to the lung injury induced by PLA_2 to some ex- tent.

CONTROL OF ANGIOGENESIS BY INHIBITOR OF PHOSPHOLIPASE A_2

Objective To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2)inhibitor-HyPE(linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid)on human bone marrow endothelial cell line(HBME-1). Methods In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated by angiogenic factor, specifically by basic fibroblast growth factor(b-FGF), vascular endothelial growth factor(VEGF),and oncostatin M(OSM)(at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube forma-tion were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel. Results HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE. Conclusions The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.

Changes of gastric and intestinal blood flow, serum phospholipase A_2 and interleukin-1β in rats with acute necrotizing pancreatitis

AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 and 0.35±0.05) mL/(min·g) was significantly lower than that in control group (0.86±0.11 and 0.85±0.06) mL/(min·g) (P<0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and 0.50±0.06) mlV(min·g) was significantly lower than that in control group (1.56±0.18 and 1.61±0.11) mL/(min·g) (P<0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20)μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07)μg/L (P<0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P<0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.

Bromophenacyl bromide,a phospholipase A_2 inhibitor attenuates chemically induced gastroduodenal ulcers in rats

AIM: To study the effect of bromophenacyl bromide (BPB), a phospholipase A2 inhibitor on gastric secretion and to protect chemically induced gastric and duodenal ulcers in rats. METHODS: Acid secretion studies were undertaken in pylorus-ligated rats with BPB treatment (0, 5, 15 and 45 mg/kg). Gastric and duodenal lesions in the rats were induced by ethanol and cysteamine respectively. The levels of gastric wall mucus, nonprotein sulfhydryls (NP- SH) and myeloperoxidase (MPO) were also measured in the glandular stomach of rats following ethanol induced gastric lesions. RESULTS: BPB produced a dose-dependent inhibition of gastric acid secretion and acidity in rats. Pretreatment with BPB significantly attenuated the formation of etha- nol induced gastric lesion. BPB also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of BPB was associated with signifi- cant inhibition of ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. These findings pointed towards the mediation of sulfhydryls in BPB induced gas- trointestinal cytoprotection. CONCLUSION: BPB possesses significant antiulcer and cytoprotective activity against experimentally induced gastroduodenal lesions.

Non-crystallographic symmetry of crystal of neutral phospholipase A_2 from Agkistrodon halys Pallas

Agkistrodotoxin, a neutral phospholipase A2 with high presynaptic neurotoxicity from the venom of Agkistrodon halys Pallas, has been crystallized by hanging drop vapor diffusion method. The crystal belongs to P21 space group with the cell dimensions a = 10.836 nm, b=8.486nm, c = 7.082nm, β=109.87$ showing C2 pseu-do-symmetry. Diffraction data to 0. 26 nm resolution have been collected on a Siemens X-200B area detector. C2 pseu-do-symmetry suggests that there exists a non-crystallographic two-fold axis parallel to crystallographic b axis. Self-rotation function calculation with different integrated radius and resolution ranges using the program POLARRFN yields four stable high peaks corresponding to three more non-crystallographic two-fold axis and one special non-crystal-lographic symmetry. The molecules in the asymmetric unit are suggested to be arranged in a manner of "dimer of dimers" by inference.

Regulatory effects of phospholipase A_2 inhibitors on platelet activating factor in endotoxic shock in rabbits

The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.

磷脂酶A_2氨基末端衍生肽的合成及其抗细菌活性的研究

目的 探讨磷脂酶A_(2)(PLA_(2))氨基末端衍生肽的合成及抗菌活性。方法 根据PLA_(2)氨基末端氨基酸残基的顺序合成为多肽PLA_(2)N_(11)、PLA_(2)N_(15)、PLA_(2)N_(20),将其分别与2种细菌(大肠埃希菌、枯草杆菌)在特定条件下培养,并以生理盐水作为对照,分析抗菌活性。结果 与对照比较,多肽不同作用浓度时PLA_(2)N_(11)、PLA_(2)N_(15)、PLA_(2)N_(20)对革兰氏阳性枯草杆菌杀菌活性更强,各多肽间比较,差异有统计学意义(P<0.05);当多肽作用浓度为500μg/ml时,PLA_(2)N_(15)对革兰氏阳性枯草杆菌杀菌活性可达99.8%,高于PLA_(2)N_(11)、PLA_(2)N_(20),及对照(P<0.05)。与对照比较,各多肽不同作用浓度时对大肠埃希菌杀菌活性比较,差异有统计学意义(P<0.05);多肽作用浓度为7.81、125.00、500.00μg/ml时,PLA_(2)N_(15)的杀菌活性均高于PLA_(2)N_(11)和PLA_(2)N_(20),及对照(P<0.05);多肽作用浓度为31.25μg/ml时,PLA_(2)N_(15)的杀菌活性低于PLA_(2)N_(11)的杀菌活性,且高于PLA_(2)N_(20)的杀菌活性(P<0.05)。结论 多肽PLA_(2)N_(11)、PLA_(2)N_(15)、PLA_(2)N_(20)对枯草杆菌、大肠埃希菌有很强的杀菌作用。

Crystal structure determination of basic phospholipase A_2 from venom of Agkistrodon halys pallas by molecular replacement method

Basic phospholipase A2 (BPLA2) from the venom of Agkistrodon halys pallas has a strong ability to hemolyze erythrocytes. The asymmetrical unit of P212121 crystal of BPLA2 contains two molecules. Self-rotation function was used to study the orientation relationship of these two molecules. Cross-rotation and translation functions were then used to determine the orientations and positions of the two molecules in the unit cell. The model building and preliminary structure refinement were carried out. The result shows that the two molecules in the asymmetrical unit of orthorhombic crystal are related by a non-crystallographic 2-fold symmetry axis.

Plasma Lysophosphatidylcholine and Phospholipase A2 Activity in Chagas Disease Patients: A Comparative Analysis

Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.

中国发生马铃薯晚疫病菌（Phytopthora infestans）A_2交配型

北京，内蒙古、山西和云南省等省区的１０个菌株，在黑麦琼脂培养基和立马豆Ｖ—８琼脂培养基上进行交配型试验，发现其中３个菌株为Ａ２交配型，７个菌株为Ａ１交配型。Ａ２交配型菌株采自内蒙古自治区和山西省。对卵孢子、藏卵器和雄器的形态进行了描述。ｔｅ，ａ＊ｆｆｎ．ＷｈｅｔｈｅｒＡ，ｅｘｉｓｔｓｏｒｎｏｔｉｎＣｈｉｎａｈａｓｎｅｖｅｒｂｅｅｎｓｔｕｄｉｅｄｂｅｆｏｒｅ．Ｉｎ１９９５ｗｅｂｅｇａｎｔｈｅｉｌｌｖｅｓｔｉｇａｔｉｏｎａｎｄｄｉｓｃｏｖｅｒｅｄＡ，ｉｎＣｈｉｎａ＇Ｔｈｅｐｒｅｌｉｍｉｎａｒｙｒｅｓｕｌｔｓｏｆｔｈｅｓｔｕｄｙｗｅｒｅｐｒｅｓｅｎｔａｓｆｏｌｌｏｗ．ＴｈｅｏｂｊｅｃｔｉｖｅｓｏｆｔｈｉｓｓｔｕｄｙｉｓｔｏｆｉｎｄｏｕｔｂｙｓｕｒｖｅｙｗｈｅｔｈｅｒｔｈｅＡ，ｍａｔｉｎｇｔｙｐｅｅｘｉｓｔｓｉｎＣｈｉｎａ，ａｎｄｆｕｒｔｈｅｒｒｅｓｅａｒｃｈｏｎｔｈｅｉｍｍｉｇｒａｔｉｏｎ，ｍｏｖｅｍｅｎｔ，ｒｅａｓｏｎｆｏｒｄｅｖｅｌｏｐｍｅｎｔａｎｄｅｐｉｄｅｍｉｏｌｏｇｙｏｆｔｈｅＡ，ｗｏｕｌｄｂｅｃａｒｒｉｅｄｏｕｔｌａｔｅｒ．１Ｍａｔｅｒｉａｌｓａｎｄｍｅｔｈｏｄｓｌ＇１ＣＯｌｌｅｃｔｉｏｎｏｆｓａｍｐ?

他克莫司联合激素治疗血清抗PLA_2R抗体持续高滴度的难治性特发性膜性肾病

目的评估他克莫司联合激素对血清抗磷脂酶A2受体(PLA2R)抗体持续高滴度的难治性特发性膜性肾病患者的疗效和安全性。方法召集12例2012年6月至2016年6月间在广州市第一人民医院行常规免疫抑制剂(环磷酰胺、霉酚酸酯或环孢素A)联合激素治疗6个月以上无效且血清抗PLA_2R抗体持续高滴度的特发性膜性肾病患者进行一项开放前瞻性研究。这12例患者被分为两组:改用他克莫司联合激素方案随访治疗12个月的他克莫司组和继续原治疗方案或改用其它常规免疫抑制剂治疗方案继续随访治疗6个月的对照组。结果在入组治疗6个月末,他克莫司组患者尿蛋白定量和血清白蛋白等临床指标均较对照组明显改善(P<0.01),e GFR也比对照组高(P<0.05);而对照组依然存在大量蛋白尿和低蛋白血症,且e GFR也较入组前有显著下降(P<0.01)。治疗6个月后,对照组无一例患者血清抗PLA_2R抗体转阴,也无一例达到临床缓解;而他克莫司组有5例(83.3%)患者血清抗PLA_2R抗体转阴,并达到临床缓解,其中2例(33.3%)完全缓解,3例(50%)部分缓解;治疗12个月后他克莫司组更有4例(66.7%)患者完全缓解。结论血清抗PLA_2R抗体持续高滴度水平,可能是部分难治性特发性膜性肾病患者对常规免疫抑制剂治疗无效的原因。他克莫司联合激素方案可能是使此类患者抗体转阴并达到临床缓解的一种有效治疗方法。

细菌感染大鼠血中血小板型磷脂酶A_2 mRNA水平的变化及其cDNA克隆

目的 观察感染大鼠血中血小板型PLA2 mRNA水平的变化 ,研究其基因和氨基酸顺序结构的特征。为开发新的抗菌药物提供依据。方法 用半定量RT PCR方法检测感染大鼠血中PLA2 mRNA ,并对PLA2 cDNA进行克隆和序列分析。结果 大鼠感染细菌后 ,血中血小板型PLA2 mRNA水平迅速明显增加 ,其DNA和氨基酸结构与其他组织来源的PLA2 有高度的同源性。结论 细菌感染可引起大鼠血中PLA2 在基因水平上的迅速反应 ,这可使血小板型PLA2 的生成增加并控制感染。血中克隆出来的PLA2 cDNA与大鼠其他组织来源的PLA2 虽略有不同 。

苦参碱对内毒素致炎大鼠PLA_2活性影响及其抗炎机制研究

目的 研究苦参碱抗炎机制和其抑制磷脂酶 A2 (PL A2 )活性的作用。方法 用 [3H]花生四烯酸掺入大肠杆菌膜为底物检测细胞内外 PL A2 方法 ,测定了苦参碱对内毒素 (L PS)造成的大鼠急性内毒素炎症时血清中分泌型磷脂酶 A2 (s PL A2 )活性和外周血白细胞中胞浆型磷脂酶 A2 (c PL A2 )活性的影响 ,同时用 Fura2 - AM作荧光指示剂检测胞内游离 Ca2 + 浓度的变化 ,并通过大鼠足跖肿胀实验证实苦参碱的抗炎作用。结果 在 L PS介导的急性内毒素血症大鼠 ,30 mg/ m L 的苦参碱 0 .2 m L ip1h对外周血 s PL A2 抑制效果最好 ,抑制率达 (81.9± 1.8) % ,此时胞内 c PL A2 活性抑制率是 (2 8.4± 6 .0 ) % ,而 Ca2 +浓度是 (15 7.10± 2 0 .5 6 ) nmol/ L,比对照升高 15 .3%。足跖肿胀实验亦证明苦参碱对炎症有显著抑制作用。结论 苦参碱是一种具有抗炎作用的新型 PL A2

黄芩甙、川芎嗪对兔感染性脑水肿与磷脂酶A_2的作用

目的探讨黄芩甙（ＢＣ）、川芎嗪（ＴＭＰＺ）、甘露醇（ＭＮ）对兔百日咳菌液（ＰＢ）脑水肿的治疗作用及机理。方法应用兔感染性脑水肿模型，用光导纤维颅连续监测硬膜外颅内压，测定血清及脑脊液（ＣＳＦ）中磷脂酶Ａ２（ＰＬＡ２）活性、脑组织含水量（ＷＣ）、伊文思蓝（ＥＢ）、钠含量及丙二醛（ＭＤＡ）与超氧化物歧化酶（ＳＯＤ）活性，观察黄芩甙、川芎嗪和甘露醇治疗对血清及ＣＳＦ中ＰＬＡ２活性的抑制作用以及与改善脑水肿的关系。结果血清及ＣＳＦ中ＰＬＡ２活性ＢＣ组和ＴＭＰＺ组明显低于ＰＢ组和ＭＮ组。脑组织含水量、伊文思蓝含量与钠含量：ＰＢ组较ＮＳ组明显增高，治疗各组均减少，依次为ＭＮ组＞ＴＭＰＺ组＞ＢＣ组。３个治疗组均能降低ＭＤＡ浓度，提高ＳＯＤ活性和减轻颅内压增高。降颅内压的作用以ＢＣ最佳，依次为ＴＭＰＺ，ＭＮ。结论ＢＣ与ＴＭＰＺ均可抑制ＰＬＡ２活性和脂质过氧化，从而减轻脑水肿与降低颅内高压。

失血性休克再灌注损伤时血浆磷脂酶A_2及其水解产物的变化

目的和方法：采用家兔失血性休克／再灌注（Ｓ／Ｒ）模型，以放射免疫法分析了动物血清中磷脂酶Ａ２及其活性产物血栓素（ＴＸＢ２）、前列环素（ＰＧＩ２）在损伤过程中的变化规律，同时观察了氯喹及其同类化合物磷酸萘酚喹、抗氧化剂黄芪酮对Ｓ／Ｒ损伤后上述ＰＬＡ２活性产物的影响。结果：氯喹可明显降低ＰＬＡ２，使ＴＸＢ２／ＰＧＩ２比值恢复于接近正常；磷酸酚喹和黄芪酮也可明显降低ＰＬＡ２，使ＴＸＢ２／ＰＧＩ２比值显著低于Ｓ／Ｒ损伤组：ＨＣＯ－３和ｔＣＯ２也得以接近于正常水平。结论：Ｓ／Ｒ过程中ＴＸＢ２的增高导致的ＴＸＢ２／ＰＧＩ２比值改变可能对循环有重要影响；氯喹类化合物及环氧化物酶抑制剂可能通过抑制ＰＬＡ２活性及降低ＴＸＢ２／ＰＧＩ２比值。

丁苯酞治疗急性脑梗死及其对血栓素A_2、前列环素及抗凝血酶Ⅲ的影响

目的观察丁苯酞治疗急性脑梗死的疗效及其对血栓素A_2(TXA_2)、前列环素(PGI_2)、抗凝血酶Ⅲ(AT-Ⅲ)的影响。方法将100例急性脑梗死患者随机分为对照组和丁苯酞组。对照组患者给予常规治疗;丁苯酞组在对照组治疗的基础上给予丁苯酞治疗。2组疗程均为21d。2组患者于治疗前后检测神经功能缺损评分(NIHSS)、日常生活能力评分(Barthel指数)、脑梗死灶体积、TXB_2、6-Keto-PGF1a及AT-Ⅲ。结果治疗21d后,丁苯酞组的总有效率90.0%高于对照组74.0%(P<0.05);丁笨酞组NIHSS评分、Barthel指数、梗死灶体积、TXB_2、6-Keto-PGF1α及AT-Ⅲ均显著改善(P<0.05,P<0.01),对照组除梗死灶体积、AT-Ⅲ外,余指标亦显著改善(P<0.05,P<0.01),丁苯酞组均优于对照组(P<0.01或P<0.05);且其不良反应轻微。结论丁苯酞联用传统药物治疗急性脑梗死安全有效,能显著改善神经功能和日常生活能力,缩小梗死灶体积,降低TXA_2,提高PGI_2及AT-Ⅲ水平。

广西眼镜王蛇毒酸性磷脂酶A_2的分离纯化和性质研究

目的 :广西眼镜王蛇毒酸性磷脂酶 A2 的分离纯化和性质研究。方法 :分离纯化采用 Sephadex G- 75 ,CM- Sepharose CL -6 B和 DEAE- Sephadex A- 5 0柱层析法 ;通过电泳 ,磷脂酶 A2 活力测定 ,氨基酸组成测定 ,N端序列分析及药理实验进行性质研究。结果 :从广西眼镜王蛇毒中分离到一种酸性的磷脂酶 A2 (命名为 APL A2 - 1) ,相对分子质量为 146 0 0 u,等电点 5 .4,酶的比活力为 10 8μmol/ m g· min- 1 ,N端序列为 NL IQFGNMIQCTVPGF。它对实验用小白鼠有致死性 (L D5 0 6 .6 m g/ kg) ,具有肌毒性 ,心脏毒性 ,抗血小板聚集活性 ,能诱导水肿形成。结论 :APL A2 - 1生化和药理性质的研究 ,为阐明蛇毒 PL A2结构和功能关系 ,及蛇伤中毒机制 ,打下了良好基础。

急性坏死性胰腺炎模型大鼠肠血流量及血清磷脂酶A_2、白介素-1β的变化

观察了急性坏死性胰腺炎 (acutenecrotizingpancreatitis ,ANP)时肠组织血流量及炎症介质的变化。实验用 96只SD大鼠 ,随机分成对照组和ANP组 ,以 5 %牛磺胆酸钠胰腺被膜下均匀注射复制ANP模型。采用放射生物微球技术在制模后 0h、2h和 12h分别测定肠组织血流量 ,同时检测血清磷脂酶A2 (PLA2 )活性及白细胞介素 1β(IL 1β)水平 ,并观察肠粘膜病理改变。结果显示 ,ANP组在制模后 2h及 12h肠组织血流量 (0 80± 0 0 7,0 5 0± 0 0 6 )mL (min·g)较对照组 (1 5 6± 0 18,1 6 1± 0 11)mL (min·g)明显减少 (均P <0 0 0 1) ,血清PLA2 活性 (94 2 9± 9 96 ,10 3 71±14 4 0 )U L ,IL 1β水平 (0 78± 0 13,0 83± 0 2 0 ) μg L较对照组 (6 5 2 7± 10 5 2 ,6 6 6 3± 9 81)U L ,(0 32± 0 0 6 ,0 33±0 0 7) μg L明显升高 (均P <0 0 0 1) ,肠粘膜损伤程度较对照组明显加重 (均P <0 0 0 1)。提示ANP早期肠组织血流量减少与炎症介质的升高同时发生 。

川芎嗪对肝缺血-再灌注损伤家兔血浆TXA_2/PGI_2水平的影响

目的:探讨川芎嗪对肝缺血-再灌注损伤家兔血浆TXA_2/PGI_2水平的影响.方法:制作家兔肝缺血-再注损伤模型,30只家兔平均分为川芎组、盐水组和对照组,应用放免法测定血浆TXB_z,6-酮基-PGF_(1(?))及其比值.结果:家兔肝缺血45min及再灌注45min血浆TXB_2.水平明显上升,6-酮基-PGF_(1(?))水平缺血45min时无明显变化,再灌注45min时显著下降,TXB_2/6-酮基-PGF_(1(?))水平增加;应用川芎嗪治疗能降低TXB_2水平,升高6-酮基-PGF_(1(?))水平,使TXB_2/6-酮基-PGF_(1(?))比值保持在正常水平.结论:川芎嗪可纠正肝缺血-再灌注后循环血中TXA_2/PGI_2的平衡失调,对肝缺血-再灌注损伤具有积极的防治作用.