抗IL-5抗体联合抗IL-13抗体对支气管哮喘小鼠气道炎症及气道高反应性的影响

目的 观察抗IL-5抗体(Anti-IL-5 Ab)联合抗IL-13抗体(Anti-IL-13 Ab)对支气管哮喘(简称哮喘)小鼠气道炎症及气道高反应性的影响,为临床应用奠定基础.方法 50只雌性Balb/c小鼠随机分成正常组、哮喘组、Anti-IL-5 Ab治疗组、Anti-IL-13 Ab治疗组和Anti-IL-5 Ab联合Anti-IL-13Ab治疗组.以清洁级Balb/c小鼠构建哮喘模型,采用腹腔注射卵蛋白和氢氧化铝混悬液处理动物.采用瑞氏染色对哮喘小鼠进行支气管肺泡灌洗液中的细胞分类及计数,应用小鼠肺功能仪检测气道阻力的变化.结果 ①Anti-IL-5 Ab联合Anti-IL-13 Ab治疗组小鼠症状较哮喘组及其他治疗组明显减轻;②Anti-IL-5 Ab联合Anti-IL-13 Ab治疗组可有效降低哮喘小鼠支气管肺泡灌洗液中嗜酸粒细胞、中性粒细胞、淋巴细胞等炎症细胞水平,与Anti-IL-5 Ab治疗组及Anti-IL-13 Ab治疗组比较差异有统计学意义(P<0.05);③Anti-IL-5 Ab联合 Anti-IL-13 Ab治疗组可有效降低哮喘小鼠气道高反应性,与Anti-lL-5 Ab治疗组及Anti-IL-13 Ab治疗组比较差异有统计学意义(P<0.05).结论 Anti-IL-5 Ab联合Anti-IL-13 Ab 治疗组不但可抑制哮喘小鼠肺部嗜酸粒细胞、中性粒细胞、淋巴细胞等炎症细胞浸润,还可以抑制哮喘迟发反应,降低气道高反应性,改善肺功能,为治疗哮喘提供新的解决办法.     

白细胞介素-13可溶性受体对支气管哮喘小鼠嗜酸粒细胞凋亡的影响

支气管哮喘(简称哮喘)是由多种细胞包括气道炎症细胞、结构细胞和细胞组分参与的气道慢性炎症性疾病[1].嗜酸粒细胞( Eos)是哮喘气道炎症的关键效应细胞.哮喘气道Eos凋亡不足或延迟是气道Eos大量浸润的成因之一.阻断IL-13信号通路可明显改善气道炎症,减轻气道高反应性(AHR).本研究中应用重组IL-13可溶性受体α2(sIL-13Rα2)治疗哮喘小鼠模型,观察BALF中Eos凋亡率及嗜酸粒细胞趋化因子(Eotaxin)表达的影响,探索sIL-13 Rα2对哮喘的治疗作用及相关机制.     

抗IL-5抗体联合抗IL-13抗体对支气管哮喘小鼠气道炎症及气道高反应性的影响

目的 观察抗IL-5抗体（Anti-IL-5 Ab）联合抗IL-13抗体（Anti-IL-13 Ab）对支气管哮喘（简称哮喘）小鼠气道炎症及气道高反应性的影响,为临床应用奠定基础.方法 50只雌性Balb/c小鼠随机分成正常组、哮喘组、Anti-IL-5 Ab治疗组、Anti-IL-13 Ab治疗组和Anti-IL-5 Ab联合Anti-IL-13Ab治疗组.以清洁级Balb/c小鼠构建哮喘模型,采用腹腔注射卵蛋白和氢氧化铝混悬液处理动物.采用瑞氏染色对哮喘小鼠进行支气管肺泡灌洗液中的细胞分类及计数,应用小鼠肺功能仪检测气道阻力的变化.结果 ①Anti-IL-5 Ab联合Anti-IL-13 Ab 治疗组小鼠症状较哮喘组及其他治疗组明显减轻;②Anti-IL-5 Ab联合Anti-IL-13 Ab 治疗组可有效降低哮喘小鼠支气管肺泡灌洗液中嗜酸粒细胞、中性粒细胞、淋巴细胞等炎症细胞水平,与Anti-IL-5 Ab治疗组及Anti-IL-13 Ab治疗组比较差异有统计学意义（P〈0.05）;③Anti-IL-5 Ab联合Anti-IL-13 Ab治疗组可有效降低哮喘小鼠气道高反应性,与Anti-IL-5 Ab治疗组及Anti-IL-13 Ab治疗组比较差异有统计学意义（P〈0.05）.结论 Anti-IL-5 Ab 联合Anti-IL-13 Ab治疗组不但可抑制哮喘小鼠肺部嗜酸粒细胞、中性粒细胞、淋巴细胞等炎症细胞浸润,还可以抑制哮喘迟发反应,降低气道高反应性,改善肺功能,为治疗哮喘提供新的解决办法.     

粉防己碱抑制支气管哮喘小鼠肺组织核因子-κB和诱导型一氧化氮合酶的研究

目的：探讨粉防己碱对支气管哮喘(简称哮喘)小鼠肺组织核因子-κB(NF-κB)、诱导型一氧化氮合酶(iNOS)表达、气道炎症和气道高反应性的影响。方法将32只 SPF 级 BALB/c 小鼠随机分为正常组、哮喘组、地塞米松组(激素组)和粉防己碱组(Tet 组)。卵白蛋白(OVA)致敏和激发建立哮喘小鼠模型。末次激发24 h 后,肺功能仪测定小鼠气道阻力;HE 染色观察气道炎症细胞浸润;ELISA 检测血清总 IgE、OVA 特异性 IgE(OVA-sIgE)及 BALF 中 Th2细胞因子 IL-4和 IL-13水平;显微镜下计BALF 中细胞总数,瑞氏染色计嗜酸粒细胞分类计数;Western blot 检测肺组织 NF-κB 和 iNOS 蛋白表达水平。结果与正常组比较,哮喘组气道阻力、气道炎症浸润、BALF 炎症细胞总数和嗜酸粒细胞分类计数、血清总 IgE 和 OVA-sIgE、BALF 中 IL-4和 IL-13以及 NF-κB 和 iNOS 蛋白表达水平均显著增高(P <0.05);与哮喘组比较,激素和 Tet 干预组上述各项指标均显著降低(P <0.05)。结论粉防己碱可下调哮喘小鼠肺组织 NF-κB 和 iNOS 表达并抑制气道炎症和气道高反应性。     

布地奈德上调支气管哮喘小鼠肺组织IDO、抑制气道炎症和气道高反应性的研究

目的 研究布地奈德对急性支气管哮喘(简称哮喘)模型小鼠肺组织吲哚胺-2,3双加氧酶(IDO)表达、气道炎症和气道高反应性的干预作用.方法 18只SPF级BALB/c小鼠随机分为正常组、哮喘组、布地奈德组.卵白蛋白(OVA)致敏和激发建立哮喘模型.末次激发24 h后,测定气道对乙酰胆碱的反应性,HE染色观察气道炎症细胞浸润,ELISA法检测血清总IgE、OVA特异性IgE(OVA-sIgE)以及支气管肺泡灌洗液(BALF) Th2细胞因子(IL-4和IL-13).Western blot检测肺组织IDO蛋白表达.结果 正常组小鼠气道阻力随乙酰胆碱浓度增加仅轻度增加,哮喘组气道阻力较正常组显著增高,布地奈德组气道阻力较哮喘组显著下降(P＜0.05);哮喘组血清总IgE和OVA-sIgE、BALF炎症细胞总数和嗜酸粒细胞分类计数、Th2细胞因子水平较正常组显著增高,布地奈德组炎症指标较哮喘组显著降低(P＜0.05);哮喘组肺组织IDO)较正常组显著下降,布地奈德组肺组织IDO较哮喘组显著增高(P＜0.05).结论 布地奈德抑制急性哮喘模型气道炎症和气道高反应性,可能与上调肺组织IDO有关.     

氧化应激与支气管哮喘气道黏液高分泌研究进展

哮喘是一种以支气管收缩可逆性、肺部炎症及气道重塑为特点的慢性气道炎症性疾病.黏液过度分泌导致气道阻塞、肺功能下降、气道重塑和感染增加.过度的活性氧/活性氮(ROS/RNS)产生造成气道炎症,气道高反应性,气道微血管高通透性和气道黏液高分泌,以及组织损伤和形态的改变.减轻氧化应激或增加抗氧化能够减轻气道嗜酸粒细胞,减少黏液分泌,减轻支气管高反应性.本文就氧化应激与哮喘气道黏液高分泌的关系作一综述.     

布地奈德上调支气管哮喘小鼠肺组织IDO、抑制气道炎症和气道高反应性的研究

目的研究布地奈德对急性支气管哮喘(简称哮喘)模型小鼠肺组织吲哚胺-2,3双加氧酶(IDO)表达、气道炎症和气道高反应性的干预作用。方法 18只SPF级BALB/c小鼠随机分为正常组、哮喘组、布地奈德组。卵白蛋白(OVA)致敏和激发建立哮喘模型。末次激发24h后,测定气道对乙酰胆碱的反应性,HE染色观察气道炎症细胞浸润,ELISA法检测血清总IgE、OVA特异性IgE(OVA-sIgE)以及支气管肺泡灌洗液(BALF)Th2细胞因子(IL-4和IL-13)。Western blot检测肺组织IDO蛋白表达。结果正常组小鼠气道阻力随乙酰胆碱浓度增加仅轻度增加,哮喘组气道阻力较正常组显著增高,布地奈德组气道阻力较哮喘组显著下降(P0.05);哮喘组血清总IgE和OVA-sIgE、BALF炎症细胞总数和嗜酸粒细胞分类计数、Th2细胞因子水平较正常组显著增高,布地奈德组炎症指标较哮喘组显著降低(P0.05);哮喘组肺组织IDO较正常组显著下降,布地奈德组肺组织IDO较哮喘组显著增高(P0.05)。结论布地奈德抑制急性哮喘模型气道炎症和气道高反应性,可能与上调肺组织IDO有关。     

氧化应激与支气管哮喘气道黏液高分泌研究进展

哮喘是一种以支气管收缩可逆性、肺部炎症及气道重塑为特点的慢性气道炎症性疾病.黏液过度分泌导致气道阻塞、肺功能下降、气道重塑和感染增加.过度的活性氧/活性氮(ROS/RNS)产生造成气道炎症,气道高反应性,气道微血管高通透性和气道黏液高分泌,以及组织损伤和形态的改变.减轻氧化应激或增加抗氧化能够减轻气道嗜酸粒细胞,减少黏液分泌,减轻支气管高反应性.本文就氧化应激与哮喘气道黏液高分泌的关系作一综述.     

卡介菌多糖核酸对支气管哮喘小鼠气道反应性及气道炎症的影响

目的 探讨卡介菌多糖核酸对哮喘小鼠气道反应性及气道炎症的影响.方法 选择Balb/c小鼠,以卵白蛋白致敏激发建立小鼠哮喘模型,设立卡介菌多糖核酸组、正常组、哮喘组.卡介菌多糖核酸按剂量具体分为1 μg,10 μg,100 μg亚组,均在第一次抗原致敏前7 d腹腔注射给药.末次激发后48 h采用美国Buxco公司小鼠整体体积扫描记法测定气道反应性,以乙酰甲胆碱各浓度激发时增强的呼吸间歇(Enhanced Pause,Penh)表示.以PC100[气道反应性升高为生理盐水(NS)值2倍时的Mch激发浓度]及Penh/NS%max综合评价气道反应性.收集支气管肺泡灌洗液,涂片后苏木素-伊红染色计数嗜酸粒细胞比例,肺组织病理检测.结果 1μg肛组PC100(13.2±6.9)g/L、10/μg组(11.8±5.58)g/L与哮喘组(5.97±1.73)g/L相比,P<0.01表示差异有统计学意义;1 μg、10 μg组Penh/NS%max分别为(623.22±252.39)%,(519.71±200.41)%,显著低于哮喘组(1 306.83±540.46)%,P<0.01.10 μg组BALF嗜酸粒细胞百分比为(42.75±7.44)%显著低于哮喘组(57.25±13.2)%,P<0.01,1 μg组、100 μg组BALF嗜酸粒细胞百分比与哮喘组相比,差异无统计学意义.结论 卡介菌多糖核酸可以显著抑制哮喘小鼠的气道高反应性及气道炎症.     

天龙咳喘灵对慢性哮喘小鼠气道重塑的影响

目的探讨中药验方天龙咳喘灵水煎剂治疗哮喘气道高反应的可能机制。方法实验设四组,盐水对照组,哮喘模型组,天龙咳喘灵治疗组和布地奈德(BUD)治疗组。小鼠经常规鸡卵清蛋白(OVA)致敏后连续18d给予1%的OVA雾化吸入激发。末次激发后24h和96h,利用体积描记仪动态观察各组小鼠气道反应性,24h-时间点取部分小鼠进行肺泡灌洗,观察肺泡灌洗液(BALF)中细胞总数和细胞分类,剩余小鼠完成96h-时间点气道反应性检测后与上述同样处理,并分离小鼠右肺制备组织切片进行病理分析。结果末次激发后24h或96h,与盐水对照组相比,OVA-哮喘组小鼠气道反应性显著升高(P0.01),相应BALF中细胞总数和嗜酸粒细胞比例也明显增加;天龙咳喘灵治疗组小鼠在24h时间点气道反应性较未治疗哮喘组无明显差别,BALF中细胞总数和嗜酸性粒细胞比例亦较正常对照组增加(P0.01),但在激发后96h气道反应性基本回到正常水平;相比之下,BUD治疗组小鼠在24h时间点气道反应性显著低于哮喘组或天龙咳喘灵治疗组(P0.01),但却在96h后气道反应性反弹上升,显著高于正常对照及天龙咳喘灵治疗组(P0.01),此时各组细胞总数和嗜酸粒细胞比例均已明显下降,且BUD治疗组仍低于天龙咳喘灵治疗组(P0.01)。肺组织病理切片显示哮喘组和BUD治疗组上皮下基底膜层明显增厚,α-SMA免疫染色显著增强,而天龙咳喘灵治疗组气道上皮下未见明显改变,α-SMA表达水平与盐水对照组无显著差别。结论不同于表面激素的抗炎效应,天龙咳喘灵水煎剂能有效防治慢性哮喘小鼠模型气道高反应性,可能主要是通过抑制肌纤维母细胞激活的抗重构作用机制。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.