老年慢性阻塞性肺病患者基质金属蛋白酶-9、转化生长因子-β和降钙素基因相关肽水平及意义

目的探讨基质金属蛋白酶(MMP)-9、转化生长因子(TGF)-β、降钙素基因相关肽(CGRP)在老年慢性阻塞性肺病(COPD)患者中的临床价值及其与肺功能的关系。方法应用美国Vmax 6200型肺功能仪测定80例健康对照组及80例COPD组(稳定期32例,急性加重期48例),应用酶联免疫吸附(ELISA)法测定3组MMP-9、TGF-β、CGRP水平。采用Pearson单因素分析MMP-9、TGF-β、CGRP与老年COPD患者肺功能的关系。结果对照组第1秒呼气量(FEV1)、最大肺活量(FVC)、FEV1/FVC值、一氧化碳弥散量(DLco)、最大通气量(MVV)显著高于COPD组(P0.05),而COPD稳定组FEV1、FVC、FEV1/FVC、DLco、MVV值高于COPD急性加重期组(P0.05)。对照组血清MMP-9、TGF-β水平显著低于COPD组,而CGRP水平高于COPD组(P0.05),而COPD稳定组血清MMP-9、TGF-β水平显著低于COPD急性加重期组,而CGRP水平高于COPD急性加重期组。经Pearson相关分析可知,MMP-9、TGF-β与FEV1、DLco、MVV呈负相关(P0.05),CGRP与FEV1、FEV1/FVC、DLco呈正相关(P0.05)。结论血清MMP-9、TGF-β、CGRP与COPD患者肺功能有密切的关系,它们在体内相互作用相互调节,共同影响气道重塑。     

维生素D辅助布地奈德治疗儿童哮喘对气道炎症及重塑影响

目的探讨维生素D辅助布地奈德治疗儿童支气管哮喘,对减轻气道炎症反应及气道重塑的影响。方法随机选取2017年6月至2019年5月于我院住院的支气管哮喘患儿96例,随机分为2组,两组均给予抗炎及对症支持等治疗基础上,A组雾化吸入布地奈德联合口服维生素D治疗,B组单独雾化吸入布地奈德治疗。随访3个月,对比两组患儿治疗前后血清IL-17、MMP-9、TIMP-1水平、肺功能情况(PEF、FVC、FEV_1)。结果治疗后两组患儿血清MMP-9水平均较前下降,A组下降明显(P0.05);血清TIMP-1水平均较前下降,A组下降显著(P0.05);血清IL-17水平均较前下降,A组下降显著(P0.05);肺功能均得到改善,A组改善明显(P0.05)。结论维生素D辅助布地奈德雾化吸入治疗支气管哮喘有效,可减少炎症因子释放、改善气道重塑,改善肺功能。     

氨茶碱对支气管哮喘气道重塑大鼠肺组织MMP-9及其基因表达的调节

目的 观察氨茶碱对支气管哮喘气道重塑大鼠气道形态学和转化生长因子β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)及其基因表达的调节作用.方法 24只SD大鼠随机分为正常组、模型组、治疗组(35 mg/kg),每组8只,除正常组外以卵蛋白致敏并吸入激发法制备大鼠哮喘模型,治疗组、模型组从第1次哮喘激发开始(第15天)分别给予氨茶碱、生理盐水1次/d灌胃给药,用药4 w后处死大鼠,取肺组织HE染色,彩色图像分析仪测量支气管壁面积、支气管平滑肌面积,采用免疫组化法测定TGF-β1含量,ELISA法测定肺组织MMP-9含量,RT-PCR法测定MMP-9 mRNA含量.结果 与正常组比较,模型组大鼠支气管壁面积、平滑肌面积、肺组织MMP-9含量及MMP-9 mRNA含量明显增加(P＜0.01);与模型组相比,治疗组大鼠支气管壁面积、平滑肌面积、肺组织TGF-β1、MMP-9、MMP-9 mRNA含量均显著降低(P＜0.01).结论 氨茶碱可通过下调哮喘气道重塑大鼠肺组织MMP-9 mRNA表达、抑制MMP-9合成、抑制TGF-β1产生从而抑制支气管哮喘大鼠气道重塑.     

肺表面活性物质对COPD大鼠模型基质金属蛋白酶-9及其抑制剂的影响

目的观察慢性阻塞性肺病（COPD）大鼠模型基质金属蛋白酶9（MMP-9）、MMP组织抑制剂（TIMP-1）表达，以及肺表面活性物质（PS）对其的影响。方法用香烟熏吸加气管内注入脂多糖法建立大鼠COPD模型，PS进行干预，观察其肺功能、肺组织病理学改变，免疫组化法检测肺MMP-9及TIMP-1表达；并设正常对照组。结果COPD组肺功能与对照组有明显统计学差异。COPD组MMP-9表达强阳性，TIMP-1轻度增多，二者比例失衡。PS干预后肺功能改善，组织损伤减轻，MMP-9阳性表达减弱，MMP-9、TIMP-1比例趋于平衡。结论PS对COPD有预防保护作用，可延缓其病情发展。     

H2松弛素对慢性阻塞性肺疾病大鼠支气管平滑肌增殖的抑制作用

目的探讨H2松弛素对慢性阻塞性肺疾病(COPD)大鼠支气管平滑肌增殖的抑制作用。方法观察正常对照组、COPD模型组及松弛素治疗组大鼠肺组织的病理变化,比较各组大鼠支气管壁及平滑肌厚度,检测基质金属蛋白酶(MMP)-1、MMP-9、基质金属蛋白酶组织抑制剂(TIMP)-1表达水平及MMP-1/TIMP-1、MMP-9/TIMP-1比值。结果与正常对照组大鼠相比,COPD模型组大鼠肺支气管壁及平滑肌厚度显著增厚,且松弛素治疗组大鼠肺支气管壁厚度及平滑肌厚度与COPD模型组大鼠相比显著降低(P0.05)。COPD模型组大鼠组织中MMP-1、MMP-9、TIMP-1的表达水平均高于正常对照组(P0.05),且MMP-1/TIMP-1、MMP-9/TIMP-1比值与正常对照组相比,呈现明显升高趋势(P0.05);而对比COPD模型组大鼠,松弛素治疗组大鼠组织中MMP-1、MMP-9、TIMP-1的表达有所降低(P0.05),且MMP-1/TIMP-1、MMP-9/TIMP-1比值与COPD模型组相比均降低(P0.05)。结论松弛素能抑制大鼠肺组织结构病理变化,抑制COPD气道平滑肌的增殖。     

异丙托溴铵联合布地奈德雾化吸入治疗慢性阻塞性肺疾病急性发作的临床疗效

目的观察异丙托溴铵联合布地奈德雾化吸入治疗慢性阻塞性肺疾病(COPD)急性发作的临床疗效。方法选取2014年2月—2016年10月湖北省中西医结合医院收治的COPD患者100例,根据治疗方案分为对照组和观察组,每组50例。对照组患者给予布地奈德雾化吸入治疗,观察组患者给予异丙托溴铵联合布地奈德雾化吸入治疗;两组患者均连续治疗7 d。比较两组患者临床疗效、治疗前后血清细胞因子水平[基质金属蛋白酶抑制因子1(TIMP1)、血管内皮生长因子(VEGF)、白介素17(IL-17)、基质金属蛋白酶9(MMP-9)]和肺功能指标[包括第1秒用力呼气容积(FEV_1)、最大呼气流量(PEF)、第1秒用力呼气容积与用力肺活量比值(FEV_1/FVC)]及治疗期间不良反应发生情况。结果观察组患者临床疗效优于对照组(P0.05)。治疗前两组患者血清TIMP-1、VEGF、IL-17、MMP-9水平比较,差异无统计学意义(P0.05);治疗后观察组患者血清TIMP-1、VEGF、IL-17、MMP-9水平低于对照组(P0.05)。治疗前两组患者FEV_1、PEF及FEV_1/FVC比较,差异无统计学意义(P0.05);治疗后观察组患者FEV_1、PEF及FEV_1/FVC高于对照组(P0.05)。两组患者治疗期间不良反应发生率比较,差异无统计学意义(P0.05)。结论异丙托溴铵联合布地奈德雾化吸入治疗COPD急性发作的临床疗效确切,可有效改善患者肺功能并降低血清细胞因子水平,有利于抑制气道重塑,安全性较高。     

益气补肾活血方对COPD稳定期患者血清MMP-9、TIMP-1的影响

目的观察益气补肾活血方对慢性阻塞性肺疾病(COPD)稳定期患者血清中基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子1(TIMP-1)的影响,客观评价其作用。方法选取2013年1月~2014年1月我院呼吸科收治的COPD稳定期患者70例作为研究对象,将其随机分为对照组和治疗组,对照组予异丙托溴铵气雾剂或河美舒利迭治疗,治疗组在对照组基础上给予益气补肾活血方治疗。分别观察治疗前后患者血清中MMP-9、TIMP-1的变化。结果两组患者治疗后血清MMP-9、TIMP-1水平明显降低,差异有统计学意义(P0.05),且治疗组含量明显低于对照组,差异有统计学意义(P0.05)。结论益气补肾活血方可有效减低COPD稳定期患者血清MMP-9、TIMP-1水平,改善COPD的气道重塑。     

氨茶碱与多索茶碱对老年慢性阻塞性肺疾病患者气道重塑及血清激活素A、转化生长因子β1水平影响的对比研究

目的比较氨茶碱与多索茶碱对老年慢性阻塞性肺疾病(COPD)患者气道重塑及血清激活素A(ACTA)、转化生长因子β1(TGF-β1)水平的影响。方法选取2014年12月—2016年12月江苏盛泽医院收治的老年COPD患者76例,采用随机数字表法分为对照组与研究组,每组38例。在常规治疗基础上,对照组患者给予氨茶碱治疗,研究组患者给予多索茶碱治疗,两组患者均连续治疗10 d。比较两组患者临床疗效,治疗前后肺功能指标、动脉血氧分压(PaO_2)、气道重塑指标及血清ACTA、TGF-β1水平,观察两组患者治疗期间不良反应发生情况。结果研究组患者临床疗效优于对照组(P0.05)。治疗前两组患者第1秒用力呼气容积(FEV1)、气道峰压(Ppeak)、呼气末二氧化碳分压(PETCO_2)、PaO_2比较,差异无统计学意义(P0.05);治疗后研究组患者FEV1、Ppeak、PETCO_2、PaO_2高于对照组(P0.05)。治疗前两组患者血清碱性成纤维细胞生长因子(b-FGF)、神经生长因子(NGF)、基质金属蛋白酶抑制因子1(TIMP-1)及基质金属蛋白酶9(MMP-9)水平比较,差异无统计学意义(P0.05);治疗后研究组患者血清b-FGF、NGF、TIMP-1、MMP-9水平低于对照组(P0.05)。治疗前两组患者血清ACTA、TGF-β1水平比较,差异无统计学意义(P0.05);治疗后研究组患者血清ACTA、TGF-β1水平低于对照组(P0.05)。研究组患者治疗期间不良反应发生率低于对照组(P0.05)。结论与氨茶碱相比,多索茶碱治疗老年COPD患者的临床疗效较优,可更有效地改善患者肺功能,抑制气道重塑并降低血清ACTA、TGF-β1水平,且安全性较高。     

不同剂量沙美特罗替卡松联合川芎嗪对慢性阻塞性肺疾病大鼠模型肺组织炎症的影响

目的探讨ICS/LABA联合川芎嗪对慢性阻塞性肺疾病(COPD)大鼠肺部炎症的干预作用。方法 70只Wistar大鼠随机分为对照组(A组)、模型组(B组)、川芎嗪组(C组)、中剂量ICS/LABA组(D组)、中剂量ICS/LABA联合川芎嗪组(E组)、高剂量ICS/LABA组(F组)、高剂量ICS/LABA联合川芎嗪组(G组),每组10只。采用烟熏加气管内注入脂多糖(LPS)法建立COPD模型。吸入ICS/LABA中、高2个剂量及川芎嗪腹腔注射进行干预。观察大鼠肺功能及肺组织病理变化,流式细胞术测定血中CD4、CD8值,酶联免疫吸附法(ELISA)测定肺泡灌洗液(BALF)中转化生长因子β1(TGF-β1)表达,免疫组化法测定肺组织中金属基质蛋白酶-9(MMP-9)、分泌性白细胞蛋白酶抑制物(SLPI)的表达,RT-PCR法检测肺组织中MMP-9 mRNA的表达。结果 B组大鼠肺泡壁破坏,肺大疱形成,间质内大量炎性细胞浸润,符合COPD肺组织病理改变,各干预组均有所减轻;B组大鼠MMP-9及其mRNA相对含量、TGF-β1浓度比A组大鼠显著升高;CD4/CD8比A组大鼠明显降低。经ICS/LABA及川芎嗪干预后,各组大鼠MMP-9及其mRNA相对含量、TGF-β1浓度与B组大鼠相比有明显降低(P<0.05);CD4/CD8、SLPI比B组大鼠有显著提高(P<0.05),以G组疗效最明显(P<0.05)。相关分析表明,MMP-9与第0.3秒用力呼气容积(FEV0.3)/用力肺活量(FVC)呈负相关(r=0.861 3,P<0.01);SLPI与FEV0.3/FVC呈正相关(r=0.832 1,P<0.01)。结论 ICS/LABA和川芎嗪均可抑制COPD大鼠肺部炎症,高剂量ICS优于低剂量ICS,且联合用药比单独用药疗效显著,其机制可能是通过降低TGF-β1、MMP-9水平并调节SLPI及CD4、CD8的表达而实现。     

孟鲁司特钠、布地奈德对哮喘小鼠气道重塑及肺组织MMP-9、TIMP-1表达的影响

目的观察孟鲁司特钠、布地奈德对哮喘小鼠气道重塑及肺组织基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制物-1(TIMP-1)表达的影响。方法将40只雌性小鼠随机分为4组各10只,模型组、孟鲁司特钠组、布地奈德组采用卵蛋白(OVA)致敏及OVA连续滴鼻激发建立哮喘模型,对照组予同等剂量生理盐水;在每次激发前30 min,孟鲁司特钠组予孟鲁司特钠0.25 mL/只(0.1 mg/mL)灌服,布地奈德组用1 mg布地奈德+8 mL生理盐水雾化吸入20 min,对照组以生理盐水进行腹腔注射及雾化吸入。HE染色观察小鼠肺组织病理变化,Image-Pro Plus6.0彩色图像分析系统测定支气管壁及平滑肌厚度,免疫组化法测定肺组织MMP-9和TIMP-1。结果对照组无支气管收缩表现,支气管组织结构正常;较对照组,模型组出现支气管收缩、黏膜充血水肿及炎症细胞浸润等情况较重,孟鲁司特钠组和布地奈德组较模型组明显减轻。与对照组比较,模型组、孟鲁司特钠组、布地奈德组支气管壁、平滑肌厚度增加,MMP-9、TIMP-1阳性率增高(P<0.05或0.01);与模型组比较,孟鲁司特钠组、布地奈德组支气管壁、平滑肌厚度减小,MMP-9、TIMP-1阳性率降低(P<0.05或0.01)。结论孟鲁司特钠和布地奈德可部分改善哮喘小鼠气道重塑并降低肺组织MMP-9和TIMP-1的表达。     

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.