中华硬蜱叮咬105kD纯化抗原免疫接种宿主后其吸血、生殖能力变化的实验研究

目的　观察中华硬蜱叮咬免疫接种宿主后的吸血、生殖能力变化。方法　选用中华硬蜱 10 5kD柱层析纯化抗原对新西兰兔进行常规免疫接种 (3次 )后 ,用中华硬蜱成虫感染 (叮咬 )新西兰兔 ,分别观察空白对照组、佐剂对照组、10 5kD纯化抗原组中华硬蜱雌性成虫的吸血、生殖情况。结果　中华硬蜱 10 5kD纯化抗原可诱导新西兰兔产生显著的抗蜱免疫力 ,使其吸血、生殖能力显著降低 ,其中吸血量较空白叮咬对照组分别下降 6 7 9%、6 5 9% ,产卵量分别下降 74 6 %、73 7% ,并且中华硬蜱吸血时间延长 ,产卵量指数降低。而中华硬蜱叮咬佐剂免疫接种组兔后 ,其吸血、生殖能力较空白对照组相比无显著性差异 (P >0 0 5 )。结论　中华硬蜱 10 5kD纯化抗原可诱导宿主产生非常有效的免疫力     

蜱抗原免疫接种诱导宿主抵抗力的研究

本文选用中华硬蜱雌性成虫中肠抗原、卵抗原对家免进行人工免疫接种，在按常规方法免疫接种三次后，用中华硬蟀成虫进行感染（叮咬），分别观察中肠抗原接种组、卵抗原接种组、佐剂对照组和空白对照组中华硬蜱的吸血量、生殖情况。结果显示．中华硬蜱叮咬中肠抗原免疫接种兔后其吸血量、产卵量均较对照组显著降低，蜱的吸血量较佐剂和空白对照组分别下降48．56％和54．65％，产卵量下降52.8％和57.9％，而中华硬蜱叮咬卵抗原免疫接种组兔后其吸血、生殖能力较对照组无显著性差异（P＜0．05）。实验表明中华硬碑中肠抗原可有效诱导宿主产生特异性抵抗力，并对该现象进行了分析讨论。     

壁细胞对H2受体拮抗剂和质子泵抑制剂耐受性研究

目的研究鼠胃黏膜壁细胞对H2受体拮抗剂和质子泵抑制剂的耐受性(脱敏)。方法用酶消化法分离壁细胞后,分为西咪替丁、法莫替丁、奥美拉唑和潘托拉唑4组,每组均包括三部分实验。其一是给予药物100mg/L干预细胞不同时间;其二是给予药物100mg/L干预细胞不同时间,然后洗涤细胞,再给予100mg/L作用1h;其三是给予不同浓度药物干预细胞2h后,洗涤细胞,再加入100mg/L作用2h。最后测定各组壁细胞H K ATP酶活力。结果H2受体拮抗剂和质子泵抑制剂均对H K ATP酶具有抑制作用;在不同干预时间下,西咪替丁1、2h组酶活性均显著高于对照组(4.96±0.247,4.63±0.054vs4.18±0.324),法莫替丁、2、4h组酶活性均显著高于对照组(3.71±0.017,5.11±0.053,4.01±0.029vs0.63±0.019);在不同干预浓度下,西咪替丁、法莫替丁0、100、1000mg/L组酶活性均显著高于对照组(分别为4.56±0.159,4.62±0.275,4.05±0.026vs3.69±0.145和3.42±0.391,4.32±0.315,4.48±0.120vs1.92±0.144);质子泵抑制剂各组无显著性差别。结论H2受体拮抗剂能够诱导壁细胞H2受体出现脱敏,质子泵抑制剂未出现耐受现象。     

组胺H2受体拮抗剂促进人胃粘膜上皮细胞的增殖和迁移

目的评价二盐酸组胺和组胺Ｈ２受体拮抗剂西咪替丁对人胃粘膜上皮细胞ＧＥＳ１增殖和迁移的影响．方法细胞增殖检测采用酸性磷酸酶细胞原位计数法．细胞迁移用细胞损伤检测法．同时，用Ｆｌｕｏ３ＡＭ为荧光标记物在粘附式细胞仪上进行了细胞内游离钙测定．结果西咪替丁浓度为１０５，１０６，１０７，１０８和１０９ｍｏｌ／Ｌ时，细胞数分别比对照组增加５８２％、６００％、７３７％和７４５％（Ｐ＜００１），细胞迁移数（１０６ｍｏｌ／Ｌ）为对照组的５９２％（Ｐ＜００５）；而组胺对细胞的增殖和迁移无明显影响．西咪替丁刺激可使ＧＥＳ１细胞内（Ｃａ２＋）ｉ浓度呈双向改变．结论西咪替丁可促进体外人胃粘膜上皮细胞的增殖和迁移，这可能是Ｈ２受体拮抗剂抗溃疡的机制之一，其途径可能部分是通过钙离子信号系统介导的．     

吸烟影响α1受体阻滞剂和Ca2+通道拮抗剂的降压疗效

目的 探讨吸烟对α1受体阻滞剂类药物和Ca2 通道拮抗剂类药物降压疗效的影响.方法 氨氯地平,特拉唑嗪单一或联合用药对入选的355例原发性高血压患者进行四周治疗,并分析吸烟史对不同降压药物降压疗效的影响.结果 单用特拉唑嗪在无吸烟史的人群中有效率达到79%,而在有吸烟史的人群中只能达到40%,且不管患者在近一年内是否戒烟,有效率均是4Q%,远低于非抽烟人群;对于单用氨氯地平的患者,有吸烟史对氨氯地平的降压疗效也有影响的趋势,但差异无统计学意义(P0.05).结论 吸烟会降低α1受体阻滞剂特拉唑嗪的降压疗效,但对Ca2 通道拮抗剂氨氯地平则无影响.     

白细胞介素－1受体拮抗剂对肺间质纤维化的影响

白细胞介素－１（ＩＬ－１）是一种具有多种生物活性的细胞因子，它参与了肺间质纤维化形成的过程。白细胞介素－１受体拮抗剂（ＩＬ－１ｒａ）能和ＩＬ－１竞争靶细胞表面受体，阻断ＩＬ－１的效应。为了探索治疗肺间质纤维化的新途径，我们在博莱霉素所致大鼠肺间质纤维化模型上，气管灌注重组人ＩＬ－１ｒａ，观察病理变化、胶原蛋白量以及转化牛长因子－βｍＲＮＡ在肺内表达的变化，评价ＩＬ－１ｒａ对肺间质纤维化形成的影响，结果发现这些指标在ＩＬ－１ｒａ治疗组和对照组间并无明显差异。     

糖皮质激素对支气管哮喘患者外周血淋巴细胞组胺受体的影响

用放射配基结合分析法，测定了泼尼松治疗前后哮喘患者外周血淋巴细胞组胺H1受体和组胺H2受体的变化，并以健康人作对照。结果发现哮喘患者外用血淋巴细胞H1R最大结合量（Bmax）显著高于健康人，而H2RBmax显著低于健康人，平衡解离常数（kd）与健康人无显著性差异。泼尼松显著下调H1RBmax，对kd无影响；显著上调H2RBmax，显著下调kd。提示，H1R数量增多，H2R数量减少可能参与哮喘发病过程。糖皮质激素能纠正组胺受体的失衡。     

白细胞介素-1β及其受体拮抗剂对系膜细胞增殖及产生一氧化氮的影响

目的：探讨白细胞介素１β（ＩＬ１β）及其受体拮抗剂（ＩＬ１ｒａ）对系膜细胞增殖及产生ＮＯ的影响。方法：培养的第１０～１２代ＳＤ大鼠肾小球系膜细胞（ＧＭＣ）用于实验,分别加入ＩＬ１β或ＩＬ１β加ＩＬ１ｒａ,１２ｈ后用化学方法测定培养上清中亚硝酸盐的含量,用３ＨＴＤＲ掺入率测定ＧＭＣ的增殖,狭缝和Ｎｏｒｔｈｅｒｎ杂交测定细胞ｉＮＯＳｍＲＮＡ表达。结果：ＩＬ１β组ＧＭＣ出现ｉＮＯＳｍＲＮＡ表达及亚硝酸盐增多（０５３±０１３ｖｓ０１８±００７ｎｍｏｌ／１０４细胞）,但无明显细胞增殖（４０４６０６±１９１２６ｖｓ３９７７９±２８０４１）;ＩＬ１β加ＩＬ１ｒａ组,无ｉＮＯＳｍＲＮＡ表达,上清亚硝酸盐含量更高（０９４±０１５ｎｍｏｌ／１０４细胞）,ＧＭＣ增殖被抑制（３１１５５±３１３９８）。结论：ＩＬ１β能刺激ＧＭＣ的ｉＮＯＳｍＲＮＡ表达和产生亚硝酸盐,ＩＬ１ｒａ虽抑制ＧＭＣ的ｉＮＯＳｍＲＮＡ表达,但没能减少其亚硝酸盐的产生。     

吸烟影响α_1受体阻滞剂和Ca~(2+)通道拮抗剂的降压疗效

目的探讨吸烟对α_1受体阻滞剂类药物和 Ca~(2+)通道拮抗剂类药物降压疗效的影响。方法氨氯地平,特拉唑嗪单一或联合用药对入选的355例原发性高血压患者进行四周治疗,并分析吸烟史对不同降压药物降压疗效的影响。结果单用特拉唑嗪在无吸烟史的人群中有效率达到79%,而在有吸烟史的人群中只能达到40%,且不管患者在近一年内是否戒烟,有效率均是40%,远低于非抽烟人群;对于单用氨氯地平的患者,有吸烟史对氨氯地平的降压疗效也有影响的趋势,但差异无统计学意义(P>0.05)。结论吸烟会降低α_1受体阻滞剂特拉唑嗪的降压疗效,但对 Ca~(2+)通道拮抗剂氨氯地平则无影响。     

血管紧张素受体拮抗剂对SHR左室肥厚的影响

目的探讨血管紧张素Ⅱ受体（ＡＴＲ）拮抗剂在左室肥厚中的作用。方法自发性高血压大鼠（ＳＨＲ）分别接受ＴＣＶ－１１６（血管紧张素Ⅱ－１受体拮抗剂）、德那脯利（Ｄｅｌａｐｒｉｌ）及ＰＤ１２３３１９（血管紧张素Ⅱ－２受体拮抗剂）治疗３周,ＷＫＹ大鼠分别接受ＴＣＶ－１１６、Ｄｅｌａｐｒｉｌ治疗３周,分别与对照组比较收缩压及左室重量与体重比（ＬＶＷ／ＢＷ）。结果ＳＨＲ实验组：口服ＴＣＶ－１１６和Ｄｅｌａｐｒｉｌ分别使收缩压下降１８．５％和１９．０％,使ＬＶＷ／ＢＷ下降７．６％和８．３％;皮下注射ＰＤ１２３３１９对收缩压及ＬＶＷ／ＢＷ均无影响。ＷＫＹ实验组：口服ＴＣＶ－１１６和Ｄｅｌａｐｒｉｌ分别使收缩压下降１１．８％和１１．１％,对ＬＶＷ／ＢＷ无影响。结论血管紧张素Ⅱ－１型受体拮抗剂ＴＣＶ－１１６能逆转ＳＨＲ左室肥厚;血管紧张素Ⅱ－２型受体拮抗剂ＰＤ１２３３１９对ＳＨＲ左室肥厚无逆转作用。     

中华硬蜱血小板集聚抑制剂的分离纯化与活性研究

目的 研究蜱类抗血小板集聚的生物活性成分，了解其与其宿主相互作用的分子机制。 方法 用葡聚糖Sephadex G?鄄50凝胶过滤及高效液相从半饱吸血的中华硬蜱（Ixodes sinensis）唾液腺中分离纯化具有血小板集聚抑制活性的蛋白质，用飞行质谱测定该抑制剂的分子量，并用兔富血小板血浆研究其血小板集聚抑制活性。 结果 通过液相分离，从中华硬蜱唾液腺中得到了一种血小板集聚抑制剂，用飞行质谱测定该抑制剂的相对分子质量（Mr ）为8 065。该抑制剂对二磷酸腺苷（ADP）诱导的血小板集聚表现强烈的抑制活性，在浓度为10 μg/mL时，可以抑制90%以上的血小板集聚。 结论 首次分离获得中华硬蜱唾液腺血小板集聚抑制剂，该抑制剂对硬蜱顺利获取宿主血餐至关重要。     

气道组胺H2受体与支气管哮喘发病机理关系的临床研究

应用组胺Ｈ２受体（Ｈ２Ｒ）激动剂甲双咪胍治疗缓解期哮喘患者１９例，观察其对气道高反应性（ＢＨＲ）的作用，以进一步探讨Ｈ２Ｒ与哮喘发病机理的关系。研究提示Ｈ２Ｒ激动剂可主要作为抗气道炎症用药，也可作为平喘药的辅助用药，说明Ｈ２Ｒ在哮喘气道炎症反应中具有保护作用。     

nm23-H_1、CerbB-2的表达与食管癌预后的关系

用免疫组化的方法分析 91例食管癌 (鳞癌 84例 ,腺癌 3例 ,未分化癌 4例 )转移抑制基因 ( nm2 3)和癌基因 Cerb B- 2蛋白表达与肿瘤临床、病理各指标间的关系 ,探讨其在食管癌发生中的相互关系和影响。结果显示 :转移抑制基因 nm2 3- H1 和原癌基因 Cerb B- 2染色均定位于细胞浆 ,两者均与淋巴结转移、预后有显著相关性 ,两者表达无相关关系。在无淋巴结转移组 ,Cerb B- 2蛋白表达亦和预后有显著负相关。认为 nm2 3- H1 高表达或 Cerb B- 2低表达者 ,淋巴结转移率低 ,术后生存率高 ,预后较好 ;Cerb B- 2可作为一个独立的预后指标 ,无论有无淋巴结转移 ,Cerb B- 2蛋白高表达预后均差     

气道组胺H2受体与哮喘发病机理关系的动物实验研究

报告（１）１０＾－６ｍｏｌ／Ｌ甲双咪胍能舒张预先用组胺诱发收缩的豚鼠气管螺旋条，用１０＾－６ｍｏｌ／Ｌ甲双咪胍预处理可使各浓度组胺诱发螺旋条最大收缩力降低、组胺累积剂量反应曲线右移。（２）地麻普利（３ｍｇ／ｋｇ）静脉注射对抗原激发引起的豚鼠肺功能降低有保护作用。提示组胺Ｈ２受体（Ｈ２Ｒ）参与气道平滑肌舒张，并通过抑制变态反应中炎性介质的释放而改善肺功能，从而在哮喘发病中起一定保护作用。     

A2β腺苷受体在支气管哮喘气道炎症中的作用及其治疗展望

内源性腺苷是一种普遍存在的信号分子，它通过至少4种特异性腺苷受体（A1、A2A、A2B和A3）调节一系列生理和病理反应。功能性A2B受体存在于与支气管哮喘（简称哮喘）发病相关的多种细胞上。本文综述A。n受体在哮喘气道炎症反应中的作用，以及2B受体拮抗剂在哮喘治疗中的地位。     

Evaluation of the Protective Effects of Histamine and 5-hydroxytryptamine Receptor Antagonists Against the Lethal Toxicity Induced by Oxygen Free Radicals in Rats

Generation of oxygen free radicals (OFR) via intravenous administration of xanthine plus xanthine oxidase [X + XO], to Inactin® anesthetized rats produced intense respiratory distress. This effect led to death of more than 90% of the animals within a 120 min observation period. Several reports documented that the two autocoids, 5-hydroxytryptamine (5-HT) and histamine (H), can induce pulmonary and bronchiolar constriction and pulmonary edema. Hence, our present studies were conducted to investigate whether antagonists of 5-HT and histamine could provide protection from the lethal toxicity of the free radicals. Pretreatment of the rats with pyrilamine and cimetidine, H1 and H2 receptor antagonists, respectively, prolonged the duration of survival, but it failed to enhance net survival rate. In contrast, pretreatment of the rats with nonspecific 5-HT antagonists, methysergide and cyproheptadine, and a selective 5-HT₂ receptor antagonist, ketanserin, markedly enhanced the survival rate to 80–90%. These observations are consistent with data showing that 5-HT levels in the systemic arterial blood doubled within 5–10 min after administration of [X + XO]. These studies support the view that OFR-mediated respiratory distress is caused predominantly by 5-hydroxytryptamine and to a lesser extent by histamine.     

Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats

AIM: To assess the effect of non-selective ETA/B (LU 302872) and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP. METHODS: Male Wistar rats with caerulein-induced AP, lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w. of each antagonist. Edema, inflammatory infiltration, necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase, and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates. RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P<0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P<0.05) vs 0.58±0.06 in untreated AP. The non selective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P<0.01) vs 1.88±0.08 in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum, autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups. %FAT/TPT in untreated AP increased about four times (18.4±3.8 vs 4.8±1.3 in control group without AP, P<0.001). Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation. CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/Band selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.     

N-Nitrosamines in gastric juice of patients with gastric ulcer before and during treatment with histamine H2-receptor antagonists

The clinical implications of N-nitrosamines (NAs) were studied by analyzing their concentration in the gastric juice of 72 healthy subjects and 279 patients with gastric ulcer before and during treatment with histamine H₂-receptor antagonists. NAs were measured by combined gas chromatography and thermal energy analyzer. The detection ratios of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in the patients were 35.3% and 34.6%, respectively, which were significantly higher than the corresponding values in healthy subjects (19.4% and 16.7%, P<0.01). Analysis among the patients showed that this trend was mainly due to higher values in patients who were given histamine H₂-receptor antagonists, as their detection ratios increased to 40.2% (NDMA) and 39.9% (NDEA). Patients without histamine H₂receptor antagonists showed moderate increases of detection ratios (NDMA; 24.2% NDEA; 22.6%) compared with healthy controls. The differences in these values between those receiving and not receiving histamine H₂-receptor antagonists were statistically significant (P<0.01). The maximum concentrations of NDMA and NDEA were 7.9 and 9.8 ng/ml in patients, and 1.2 and 1.3 ng/ml in healthy subjects (the difference between the 2 groups P<0.02). These results indicated that patients with gastric ulcer had higher detection ratios and concentrations of NDMA and NDEA in gastric juice and that, while significant increases occurred during treatment with histamine H₂-receptor antagonists, the extent of increase was below toxic or experimental carcinogenic levels.     

虫卵ITS-2序列分析鉴别华支睾吸虫和扇棘单睾吸虫的研究

目的建立以分子生物学技术为基础的华支睾吸虫与扇棘单睾吸虫的ITS-2序列分析鉴别方法。方法在华支睾吸虫流行区采集华支睾吸虫和扇棘单睾吸虫成虫,从成虫虫体分离并收集虫卵。以蛔虫、鞭虫、钩虫、蛲虫做对照虫种,按不同虫种和虫卵数分成5个实验组,各组分别提取DNA,并扩增ITS-2序列,对扩增产物进行测序并作同源性分析以确保为目标片段,根据PCR扩增产物电泳获得的条带判定虫种。结果以华支睾吸虫和扇棘单睾吸虫虫卵DNA为模板的PCR产物电泳图谱分别在400bp、500bp左右各显示一条明显条带;在以两种虫卵DNA混合液为模板的PCR产物中,电泳图谱在400bp左右和500bp左右各显示明显条带。将测序得到的两种核苷酸序列进行Blast比对后,显示与GenBank中相应的华支睾吸虫和扇棘单睾吸虫序列高度同源。混入四种肠道线虫虫卵DNA的PCR产物中,除目的条带外,无其他条带。结论该方法可以对华支睾吸虫及扇棘单睾吸虫虫卵进行鉴别,且结果不受常见四种肠道线虫虫卵干扰,敏感性和特异性较高,可作为两虫种的鉴别检测方法。