鱼腥草注射液过敏及类过敏实验研究

目的 评价鱼腥草注射液及其辅料吐温80(Tween-80)静脉给药的致敏性。方法 采用Beagle犬类过敏及过敏实验,观察给药后动物行为变化和检测血浆中组胺、IgE、IgM、IgG的含量。结果 含有Tween-80的鱼腥草注射液及Tween-80组动物给药后出现显著的行为异常,血浆组胺升高,而IgE变化不规律,IgG、IgM则无明显改变。结论 鱼腥草注射液中导致犬严重类过敏反应与Tween-80有关。建议Beagle犬的过敏及类过敏试验,应作为中药注射液致敏试验的必做实验,行为异常及血浆中组胺为主要的判定指标,IgE作为辅助判定指标。     

鱼腥草注射液过敏及类过敏实验研究

目的评价鱼腥草注射液及其辅料吐温80（Tween-80）静脉给药的致敏性。方法采用Beagle犬类过敏及过敏实验,观察给药后动物行为变化和检测血浆中组胺、IgE、IgM、IgG的含量。结果含有Tween-80的鱼腥草注射液及Tween-80组动物给药后出现显著的行为异常,血浆组胺升高,而IgE变化不规律,IgG、IgM则无明显改变。结论鱼腥草注射液中导致犬严重类过敏反应与Tween-80有关。建议Beagle犬的过敏及类过敏试验,应作为中药注射液致敏试验的必做实验,行为异常及血浆中组胺为主要的判定指标,IgE作为辅助判定指标。     

齐墩果醇酸对过敏性休克的对抗作用

研究齐墩果醇酸(oleanolic acid,OA)对6-氨基青霉烷酸APA-蛋白致敏豚鼠过敏休克的对抗作用.方法:采用腹腔注射抗原建立豚鼠过敏休克模型,同种被动皮肤过敏反应(PCA)测定致敏豚鼠血清抗体滴度,荧光测定致敏豚鼠肺组胺含量,大鼠颅骨骨膜法测定肥大细胞脱粒率.结果:OA可明显降低APA-蛋白致敏豚鼠过敏休克的发生率和死亡率.抑制致敏豚鼠血清抗APA-抗体生成;降低肺组胺含量;抑制豚鼠PCA反应及大鼠颅骨骨膜肥大细胞脱颗粒.结论:OA对抗过敏休克作用机制与其抑制血清抗APA抗体生成,并降低组胺含量有关.     

鱼腥草注射液新制剂致敏性评价实验研究

目的:采用Beagle犬致敏实验研究来评价鱼腥草注射液新制剂(new Houttuynia Cordata injec-tion,NYI)的致敏性。方法:在类过敏和过敏试验中,通过静脉注射不同剂量的NYI,观察给药后Beagle犬的行为学变化,检测血浆中组胺、IgE的含量变化。结果:NYI在致敏给药后未出现明显的行为异常,类过敏试验中血浆组胺和IgE升高不明显,在过敏试验中血浆组胺和IgE未见升高。结论:NYI对Beagle犬未发现有明显的过敏性反应,为临床安全用药提供了实验依据。     

鱼腥草注射液的被动皮肤过敏试验及体外过敏试验

目的探索鱼腥草注射液中的过敏原及其致敏机制,并建立药物过敏原筛选的方法。方法分别用鱼腥草注射液、鱼腥草蒸馏液、吐温80、阴性对照物和阳性对照物对BALB/C小鼠、SD大鼠进行异种被动皮肤过敏试验,并对RBL-2H3细胞进行体外致敏试验。检测BALB/C小鼠和BN大鼠抗血清中IgE的含量、被动皮肤过敏反应中大鼠蓝斑直径大小及体外致敏实验中肥大细胞的脱颗粒反应。结果鱼腥草注射液A组、鱼腥草注射液B组、吐温80组、鱼腥草蒸馏液组和阳性对照组的BALB/C小鼠和BN大鼠血清中的IgE水平均显著升高。当BALB/C小鼠抗血清稀释比例为1∶2时,SD大鼠被动皮肤过敏反应均呈阳性;BALB/C小鼠抗血清稀释比例为1∶8时,仅鱼腥草注射液B组和阳性对照组SD大鼠呈阳性;BALB/C小鼠抗血清稀释比例为1∶32时,各组SD大鼠均未见阳性。体外过敏试验结果显示:鱼腥草注射液组、吐温80组、鱼腥草蒸馏液组和阳性对照组的肥大细胞脱颗粒百分率、β-氨基己糖苷酶释放率和上清中组胺释放量,与阴性对照组相比均有显著性增加。结论吐温80为鱼腥草注射液的主要过敏原,其致敏机制是由IgE介导的,经过吐温80的首次致敏和二次激发出现有细胞因子及炎性介质参与的机体异常的免疫调节,引起一系列过敏症状。鱼腥草蒸馏液中含有其他引起过敏反应的过敏原。体外过敏试验结果与动物试验结果一致,体外致敏模型可用于药物过敏原的筛选。     

复尔康注射液主动全身过敏试验研究

目的观察复尔康注射液给予动物后主动全身过敏情况,对复尔康注射液的安全性进行评价。方法以豚鼠腹腔注射致敏,分别于首次致敏后第14天和21天以致敏量的2倍进行激发,激发后详细观察记录每只动物的反应情况。结果复尔康高、低剂量组豚鼠均呈现弱阳性反应,补充实验豚鼠亦呈现类过敏反应。结论复尔康注射液豚鼠静脉给药后出现的过敏症状属于类过敏反应范畴,不能判断为主动全身过敏反应。     

几种临床引发Ⅰ型过敏反应的中药注射剂致敏性再评价

目的 通过主动全身过敏试验（ASA）及被动皮肤过敏试验（PCA）对几种临床易于发生Ⅰ型过敏反应的中药注射剂的致敏性进行再评价.方法 取生理盐水、卵蛋白、清开灵注射液、生脉注射液、丹参注射液、喜炎平注射液对豚鼠进行主动全身过敏试验和大鼠被动皮肤过敏试验：（1）Elisa法检测主动全身过敏试验中采集的豚鼠血浆中IgE、组胺、类胰蛋白酶、β-氨基己糖苷酶的含量.（2）观察被动皮肤过敏试验中大鼠背部出现的蓝斑情况.结果 主动全身过敏试验中卵蛋白组、生脉注射液组、丹参注射液组豚鼠血浆中IgE、组胺及β-氨基己糖苷酶含量均高于生理盐水组;被动皮肤过敏试验中卵蛋白组、生脉注射液组、丹参注射液组可见明显蓝斑.结论 主动全身过敏试验结合被动皮肤过敏试验表明卵蛋白、生脉注射液、丹参注射液、清开灵注射液有致敏性,可引起Ⅰ型过敏反应的发生.     

黄芩苷的致过敏作用机制

目的：黄芩苷是双黄连粉针剂的主要有效成分,有报道称双黄连注射液过敏反应与黄芩苷有关,本研究旨在阐明黄芩苷的致过敏作用机制,探索一种能够避免多种中药制剂引起过敏的方法。方法：本文采用活性酯法制备黄芩苷全抗原,建立黄芩苷致豚鼠过敏性变态反应的动物模型;通过被动皮肤过敏反应试验（PCA）、豚鼠肥大细胞脱颗粒、离体回肠收缩试验分析黄芩苷致过敏作用的变应原性;采用酶联免疫吸附试验和放射过敏原吸附试验测定血清中黄芩苷特异性抗体。结果：黄芩苷与牛血清蛋白（BSA）、人血清白蛋白（HSA）耦联成功。致敏豚鼠激发后,迅速出现呼吸困难、小便失禁直到呼吸停止死亡等症状,组织HE染色显示豚鼠出现了典型的速发型过敏反应特征。被动皮肤过敏反应试验表明致敏豚鼠体内同时存在黄芩苷特异性IgE和IgG型抗体,IgE和IgG两抗体之间无相关性。19只致敏豚鼠特异性IgG抗体阳性率为84％,特异性IgG水平与特异性IgG抗体效价之间有相关性（P〈0．05）。     

鱼腥草注射液中过敏原成分

目的探索鱼腥草注射液中的过敏原成分及其致敏机理。方法分别用鱼腥草注射液、鱼腥草蒸馏液、吐温80、阴性对照物和阳性对照物对豚鼠和Brown Norway(BN)大鼠进行全身主动过敏试验,并用吐温80首次静脉注射豚鼠和BN大鼠进行类过敏试验。观察其行为学反应并检测动物血清中组胺、IL-4、IgE、IgG和IgM的水平。结果阳性对照组、鱼腥草注射液组、吐温80组和鱼腥草蒸馏液组动物都观察到不同程度的行为学过敏反应,且动物血清中的组胺、IgE和IL-4水平,以及阳性对照组和吐温80组的BN大鼠血清中IgM水平与阴性对照组相比显著性升高,IgG、IgM及鱼腥草蒸馏液组BN大鼠血清中组胺和IL-4水平无显著变化。吐温80类过敏试验组,动物的行为学及血清中各生化指标均未见显著变化。结论吐温80为鱼腥草注射液中的主要过敏原,可以引起豚鼠和BN大鼠发生Ⅰ型全身主动过敏反应,而不引起豚鼠和BN大鼠发生类过敏反应。鱼腥草蒸馏液中含有其他引起过敏反应的过敏原。     

鱼腥草注射剂过敏反应机制的实验研究

目的：探讨鱼腥草注射剂过敏反应的发生机制。方法：制备鱼腥草素和新鱼腥草素全抗原,建立豚鼠过敏反应模型,采用PCA和ELISA方法测定致敏豚鼠血清特异性IgE和IgG抗体。结果：鱼腥草素组和新鱼腥草素组致敏豚鼠经激发后,两致敏组过敏反应发生率分别为80％和90％,休克发生率分别为20％和50％,死亡率分别为20％和40％,致死豚鼠的肝肺组织病理均呈现典型的过敏性休克变化特征;致敏豚鼠血清特异性IgE和IgG抗体均在第23天达到高峰,两组抗体效价与过敏反应分级均呈显著性相关（P〈0．01）,IgE和IgG抗体效价之间无相关性（P〉0．05）;ELISA和PCA所测特异性IgG效价之间存在相关性（P〈0．05）;被动致敏肥大细胞经抗原攻击后,肥大细胞脱颗粒率均显著高于阴性对照组（P〈0．01）;两组致敏豚鼠离体回肠经抗原攻击后,肠管收缩明显增强,并能被苯海拉明所阻断。结论：鱼腥草注射剂过敏反应的发生与鱼腥草素和新鱼腥草素的过敏原性有关,其发生机制与特异性IgG、IgE抗体产生、肥大细胞等释放过敏介质有关。     

Monoclonal murine anti-DNP IgE: in vitro histamine release of rat mast cells in the presence of reaginic rat and mouse sera

Mast cells from normal rats and animals reinfected with Nippostrongylus brasiliensis (N.b.) were sensitized in vitro with monoclonal anti-DNP mouse IgE, reaginic mouse serum with ovalbumin (OA) specificity and reaginic rat serum against N.b. The sensitized cells were triggered for the release of histamine with DNP-bovine-serum-albumin (DNP-BSA), OA, N.b.-homogenate and guinea-pig anti-mouse IgE. The histamine release from normal mast cells sensitized with monoclonal mouse IgE was inhibited either with N.b.-reaginic rat serum or OA-reaginic mouse IgE (30 micrograms/10(5) mast cells) completely desensitized mast cells from reinfected rats for specific histamine release in the presence of either N.b.-antigen or DNP-BSA. Anti-mouse IgE which was prepared by monoclonal mouse IgE did not bind to rat mast cells sensitized with rat IgE as was revealed by immunofluorescence experiments. Consequently we observed that anti-mouse IgE failed to trigger the histamine release from mast cells of reinfected rats.     

Histamine release from the mast cells of guinea-pig lung

The distribution of mast cells and the effects of antigen on the mast cell population of sensitized guinea-pig lung have been examined. Doses of antigen, phospholipase A, trypsin, and compound 48/80 which released similar amounts of histamine also caused mast cell damage to similar extents following in vitro or in vivo administration. Pretreatment with ethanolamine, hydrocortisone or theophylline reduced the release of histamine and of srs-a , and mast cell damage during subsequent anaphylaxis. Whilst there is evidence that the mast cell might be a selective target for the anaphylactic reaction in guinea-pig lung tissues, there is also evidence to suggest that the anaphylactic reaction induces generalized cell damage in these tissues.     

Asthma. The mast cell.

The mast cell's association with asthma has a long history dating back to the turn of the century, when Dale and Laidlaw described histamine as a spasmogen for guinea-pig airways and a proposed mediator of acute anaphylaxis. Almost half a century elapsed before histamine was localised to the granules of mast cells, although the release of this and other mediators of the acute allergic reaction were known to involve reagin subsequently identified as IgE. The biochemical mechanisms involved in transduction signalling not only results in the calcium and energy-dependent release of preformed mediators by degranulation but also the generation and subsequent release of an array of newly formed products, many of which are derived from phospholipid precursors.     

The effect of ethanol administration into the mouse on mast cell histamine releasability in vitro

Both chronic and acute ethanol administration to the mice (resulting in blood ethanol level 74.0 +/- 8.0 and 79.2 +/- 8.7 mM respectively) induced partial inhibition of in vitro histamine secretion from their peritoneal mast cells challenged with anti-mouse IgE or concanavalin A. An inhibiting effect of chronic ethanol administration was not observed when mast cells were in vitro challenged with calcium ionophore A23187. The results may suggest that ethanol intoxication of the mice inhibits in vitro anaphylactic histamine release from their peritoneal mast cells by the alteration of an early stage of biochemical processes leading to the opening of calcium channels in cell membrane and subsequent mediator secretion.     

Correlations between histamine and opioid peptides on the modulation of inflammatory processes in rats exposed to stress

The role of mast cell histamine in body reactivity of rats under experimental stressful conditions was studied. Animals submitted to chronic anaphylactoid reactions (by injecting compound 48/80 at the dose of 1 mg/kg, i.p., twice daily, for five days), when exposed to cold-restraint stress, exhibited a fully evident inflammatory response in the carrageenin-oedema test, whereas saline-treated rats, under the same experimental conditions, showed reduced paw oedema. Interestingly, a single injection of compound 48/80 increased the pituitary content of Beta-endorphin(ir), but chronic administration failed to produce this effect suggesting that some adaptation of the organism to repeated anaphylactoid reactions may occur. These results support the hypothesis of correlations between pituitary Beta-endorphin and mast cell histamine in the reactivity of the organism to stressful stimuli.     

Histamine release from mast cells of various species induced by histamine releasing factor from human lymphocytes

The aim of our work was to investigate the effect of histamine releasing factor (HRF), produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics, on mast cells of various species (mouse - peritoneal mast cells, hamster and rat - peritoneal and pleural mast cells, guinea-pig - mesenteric and pulmonary mast cells). We found that human HRF is able to release histamine from the examined mast cell populations in a dose-dependent fashion. Mast cells from various species differed in their susceptibility to the action of HRF; rat pleural and guinea-pig mesenteric and pulmonary mast cells were the most susceptible, while mouse and hamster peritoneal mast cells - the least susceptible. The presence of 50% D2O in the medium significantly increased HRF-induced histamine release from rat mast cells, while the addition of phosphatidylserine did not change it. HRF-induced histamine release from guinea-pig mesenteric mast cells was not related to sensitization of these cells. We also compared histamine release from guinea-pig pulmonary and mesenteric mast cells induced by human HRF produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics. We have found that supernatant from atopic asthmatics lymphocyte cultures released significantly more histamine than supernatant from non-atopic asthmatics lymphocyte cultures. Our studies give evidence that human HRF acts across the species barrier and induces histamine release from mast cells of various species. The mechanism of HRF action on mast cells seems to be different from that of allergen.     

注射用替加环素临床前安全性研究

目的 评价注射用替加环素的安全性。方法 对注射用替加环素进行血管刺激、肌肉刺激、溶血性及被动皮肤过敏、全身主动过敏性、类过敏性试验。结果 注射用替加环素对血管无明显刺激性、对肌肉组织产生轻度可逆性的刺激,对家兔红细胞无溶血、凝聚作用,大鼠被动皮肤过敏反应（PCA）试验未出现过敏反应;豚鼠全身主动过敏反应（ASA）试验部分豚鼠出现过敏反应;注射用替加环素与已上市药品Tygacil 在同等剂量下,豚鼠出现同等程度的类过敏反应。结论 注射用替加环素可能会引起肌肉刺激性及过敏、类过敏反应,临床应用时应关注患者给药后的反应。     

Effect of triphenyltin chloride on the release of histamine from mast cells

The effects of triphenyltin chloride (TPTC) on the release of histamine from rat and mouse mast cells in vitro and in vivo were investigated. The results obtained are summarized as follows: (a) At doses between 1 and 3 mg/kg, TPTC inhibited the dye leakage due to passive cutaneous anaphylaxis mediated by IgE antibody in mouse ear. At the same doses, TPTC inhibited the swelling due to reversed cutaneous anaphylaxis mediated by IgG antibody in rat. However, TPTC did not affect dye leakage due to histamine, serotonin, and LTC₄ in rat skin; (b) Histamine release by antigen and IgE antibody in rat peritoneal cavity was inhibited by the administration of TPTC at doses between 0.3 and 3 mg/kg; (c) Histamine release by calcium ionophore A 23187 from purified rat peritoneal mast cells in vitro was inhibited by TPTC at concentrations between 10^–7 and 10^–6 M. At the same concentration, TPTC, itself, caused neither the release of histamine nor any change in cell viability which was supported by the activity of lactate dehydrogenase (LDH) from purified rat peritoneal mast cells. All this evidence suggests that TPTC has an inhibitory effect on the release of histamine from mast cells without direct cytotoxicity.