巨噬细胞炎症蛋白-1α在机械通气致大鼠急性肺损伤中的作用

目的 观察巨噬细胞炎症蛋白-1α(MIP-1α)在不同潮气量机械通气致大鼠急性肺损伤发病中的作用.方法 24只雄性健康Wistar大鼠随机分为对照组、小潮气量组和大潮气量组.分别检测各组大鼠支气管肺泡灌洗液(BALF)中性粒细胞计数、BALF和血浆髓过氧化物酶(MPO)活性和MIP-1α含量以及肺组织MIP-1α蛋白表达水平.结果 大潮气量组大鼠BALF中性粒细胞计数、MPO活性及MIP-1α含量均明显高于对照组和小潮气量组(P值均<0.01).大潮气量组大鼠肺泡上皮和细支气管上皮细胞MIP-1α蛋白表达水平明显高于对照组和小潮气量组(P值均<0.01).对照组与小潮气量组各项指标比较差异无统计学意义.相关分析结果表明,各组大鼠BALF中MIP-1α含量与中性粒细胞计数及MPO活性均呈正相关(r=0.803,r=0.791,P值均<0.05).结论 趋化性细胞因子MIP-1α促使中性粒细胞在肺内募集、活化是导致呼吸机所致肺损伤发病的重要因素之一;呼吸机所致肺损伤病变部位不仅仅局限于肺泡,对细支气管也有一定损伤作用.     

巨噬细胞炎症蛋白-1α在机械通气大鼠肺泡巨噬细胞中的表达

目的 通过检测不同潮气量机械通气大鼠肺泡巨噬细胞炎症蛋白-1α(macrophage inflammatory protein-1α,MIP-1α)和核因子κB(nuclear factor-kappa B,NF-κB)p65蛋白表达水平,探讨肺泡巨噬细胞(AM)活化在呼吸机所致肺损伤(VILI)中的作用.方法 32只雄性Wistar大鼠随机分为对照组、小潮气量组、常规潮气量组和大潮气量组.采用SABC法分别测定各组大鼠BALF肺泡MIP-1α及NF-κB p65蛋白表达水平.并用100-CX型透射电镜观察其AM的超微结构.结果 大潮气量和常规潮气量组大鼠BALF肺泡MIP-1α及NF-κB p65蛋白染色阳性细胞百分比均明显高于对照组和小潮气量组(P＜0.01);大潮气量组大鼠BALF肺泡MIP-1α及NF-κB p65蛋白染色阳性细胞百分比与常规潮气量组比较亦有显著差异;小潮气量组与对照组比较差异无统计学意义(P＞0.05).透射电镜下显示,大潮气量和常规潮气量组大鼠AM呈功能激活状态.结论 AM是引起VILI的始动细胞之一,在VILI的发病中具有重要作用;AM活化并释放MIP-1α是引起肺内PMN聚集、活化,导致VIL1发生的一个重要因素;AM表达与释放MIP-1α在某种程度上可能受NF-κB的调控.     

核因子κB在呼吸机致急性肺损伤大鼠肺组织巨噬细胞炎症蛋白-1α表达中的作用

目的 通过观察不同潮气量机械通气大鼠肺组织核因子κB(NF κB)p65蛋白和巨噬细胞炎症蛋白-1 α(MIP-1α)mRNA表达水平,探讨NF-κB活化对呼吸机致急性肺损伤大鼠肺组织MIP-1α表达的调控作用.方法 24只雄性健康Wistar大鼠随机分为对照组、小潮气量组和大潮气量组.分别采用原位杂交和免疫组织化学染色法检测各组大鼠肺组织MIP-1α mRNA及NF-κB p65蛋白的表达水平.结果 大潮气量组大鼠肺组织细支气管上皮NF-κB p65蛋白和MIP-1α mRNA阳性表达细胞百分比均明显高于小潮气量组和对照组(P值均<0.01).对照组与小潮气量组比较差异无统计学意义.相关性分析结果表明,各组大鼠细支气管上皮NF-κB p65蛋白阳性表达细胞百分比与MIP-1α mRNA阳性表达细胞百分比之间呈正相关(r=0.482,P<0.05).结论 大潮气量机械通气引发肺组织MIP-1α mRNA高表达在呼吸机所致肺损伤发生中具有一定作用,肺组织MIP 1α表达在一定程度上可能受NF-κB的调控.     

机械通气对大鼠肺组织SP—A表达的影响及氨溴索的干预作用研究

目的通过观察氨溴索对机械通气致大鼠急性肺损伤时肺表面活性蛋白A（SP—A）表达的影响,探讨SP-A在呼吸机所致肺损伤（VILI）发生过程中的作用,以及氨溴索对VILI的防治作用。方法健康Wistar大鼠24只,随机分为对照组、机械通气组（MV组）和氨溴索干预组（AMB组）。观察各组大鼠肺组织病理学变化,检测支气管肺泡灌洗液（BALF）中性粒细胞记数,采用考马斯亮蓝法测定BALF蛋白含量,采用反转录聚合酶链反应（RT—PCR）和免疫组织化学染色法测定肺组织SP—A mRNA及其蛋白的表达。结果MV组大鼠BALF中性粒细胞计数、BALF蛋白含量较对照组和AMB组明显升高（P〈0．01）,而肺组织SP-A mRNA及其蛋白表达水平较对照组和AMB组明显降低（P〈0．01）;对照组上述指标与AMB组比较差异无统计学意义（P〉0．05）。结论SP—A在VILI的发生、发展过程中具有重要作用,氨溴索可通过促进SP—A表达,减轻肺组织损伤,对VILI有一定保护作用。     

脑肠肽 Ghrelin 对呼吸机相关性肺损伤大鼠的保护作用机制研究

目的：研究脑肠肽 Ghrelin 预处理对呼吸机相关性肺损伤大鼠的保护作用及机制。方法36只雄性 Sprague-Dawley 大鼠,体质量(300±20)g,随机分为3组(n =12);对照组;呼吸机相关性肺损伤组(VILI)组;Ghrelin 预处理组。其中对照组给予常规机械通气(通气设置：潮气量10 ml/kg,频率40次/分,吸入氧浓度21%),VILI 组和 Ghrelin 预处理组给予高潮气量机械通气(通气设置：潮气量30 ml/kg,频率40次/分,吸入氧浓度21%)。Ghrelin 预处理组在行机械通气前30 min 皮下注射50 ng/kg Ghrelin,对照组和 VILI 组于机械通气前30 min 皮下注射等体积生理盐水;所有动物在机械通气4 h 后处死,取肺组织,光镜检查病理改变,计算肺湿干比重及检测组织髓化过氧化物酶(MPO)水平,收集 BALF,检测总蛋白总量和炎性因子肿瘤坏死因子α(TNF-α)和 IL-6的水平,取血液标本行血气分析并计算氧合指数(PaO 2/FiO 2)。结果光镜下可见：同对照组相比, VILI 组肺组织病理损伤严重,BALF 中蛋白总量及炎性因子 TNF-α和 IL-6水平明显升高(P 值均<0.05),肺组织湿干比及 MPO 水平明显升高(P <0.05),氧合指数明显降低(P <0.05)。而经Ghrelin 处理后的 VILI 大鼠肺组织病理学改变明显减轻,BALF 中蛋白总量及细胞计数均较 VILI 组明显降低,氧合指数明显改善(P <0.05)。结论皮下注射脑肠肽 Ghrelin 可降低呼吸机相关性肺损伤,其主要作用机制是通过抗炎而发挥保护作用的。     

不同潮气量机械通气对大鼠肺组织激活蛋白-1、γ-谷氨酰半胱氨酸合成酶的影响

目的通过观察不同潮气量机械通气对大鼠肺组织激活蛋白-1（AP-1）和1-谷氨酰半胱氨酸合成酶（γ—GCS）表达的影响,探讨氧化-抗氧化系统失衡在呼吸机所致肺损伤（VILI）发生中的作用。方法24只雄性Wistar大鼠随机分为对照组、小潮气量（L—VT）组和大潮气量（H—VT）组,每组8只。光镜下观察各组大鼠肺组织病理损伤程度;采用硫代巴比妥酸比色法测定大鼠血浆及肺组织中丙二醛（MDA）含量,原位分子杂交技术和免疫组织化学染色法检测肺组织AP-1和γ-GCSmRNA及其蛋白表达水平。结果H—VT组大鼠肺组织和血浆中MDA含量明显高于对照组和L—VT组（均P〈0．01）,肺组织病理损伤程度较对照组和L—VT组明显加重;L—VT组与对照组比较差异无统计学意义（P〉0．05）。H—VT组肺组织γ-GCSmRNA及其蛋白表达水平明显低于对照组和L—VT组（均P〈0．01）,而AP-1mRNA及其蛋白表达水平明显高于对照组和L—VT组（均P〈0．01）,L—VT组与对照组比较差异均无统计学意义（P〉0．05）。结论大潮气量机械通气通过上调肺组织AP-1mRNA及其蛋白表达,抑制γ-GCS活性,导致肺组织局部谷胱甘肽合成减少和氧化-抗氧化系统失衡,可能是VILI发生的重要因素之-。     

卡托普利对大潮气量机械通气大鼠肺组织细胞凋亡的影响

目的 通过观察大潮气量机械通气大鼠肺组织细胞凋亡水平和肺内血管紧张素Ⅱ(AngⅡ)含量的变化,探讨血管紧张素转换酶抑制剂——卡托普利对呼吸机所致肺损伤(VILI)的防治作用.方法 雄性Wistar大鼠30只,随机分为对照组、大潮气量机械通气组(H-VT)和卡托普利干预组(CAP).观察各组大鼠肺组织病理学改变,测定其急性肺损伤(ALI)评分、支气管肺泡灌洗液(BALF)总蛋白含量和肺湿/干重比值(W/D).采用DNA断端末端标记法(TUNEL)检测肺组织细胞凋亡指数,采用ELISA法检测肺组织AngⅡ含量.结果 H-VT组大鼠肺组织ALI评分、W/D,BALF总蛋白含量、肺组织AngⅡ含量及细胞凋亡指数均明显高于对照组(P值均＜0.01),且出现明显肺组织病理学改变.CAP组大鼠肺组织上述指标均较H-VT组明显降低(.P值均＜0.01),同时肺组织病理学改变也较H-Vr组明显减轻.结论 肺组织细胞凋亡在VILI发病中具有重要作用,卡托普利可通过降低大潮气量机械通气大鼠肺组织细胞凋亡水平,对V1LI起一定保护作用.     

大鼠呼吸机相关肺损伤自噬相关蛋白的表达及意义

目的探讨大鼠呼吸机所致肺损伤(VILI)过程中自噬相关蛋白的表达及意义。方法健康雄性SPF级SD大鼠30只,7周龄,体重(220±20)g,实施麻醉和气管切开术后分别接受不同潮气量(VT)的通气(通气时间均为4 h)。随机分为三组:对照组(A组,仅切开气管保留自主呼吸);常规通气组(B组,VT=10 ml/kg);损伤通气组(C组,VT=40 ml/kg)。A组在气管切开即刻,其他组在机械通气结束后放血处死动物,Western印迹检测肺组织Beclin1和LC3的表达,计算肺湿/干比重(W/D比值)、MPO活性及肺泡灌洗液中总蛋白含量,光镜下行白细胞计数。结果在大潮气量机械通气4 h后,肺组织中总蛋白、W/D、白细胞计数和MPO等指标均显著增加(P0.05);肺组织中Beclin1、LC3表达水平(1.21±0.11、0.91±0.11)均显著增加。结论自噬表达的增加参与了大鼠VILI的发生。     

卡托普利对大潮气量机械通气大鼠肺组织小窝蛋白-1表达的影响

目的通过观察血管紧张素转换酶抑制剂-卡托普利干预后大鼠肺组织血管紧张素Ⅱ（AngⅡ）及小窝蛋白-1（Cav-1）表达量的变化,探讨卡托普利对大潮气量机械通气致大鼠急性肺损伤的防治作用。方法24只健康雄性sD大鼠,随机分为对照组、大潮气量通气组（H—VT）和卡托普利干预组（CAP）,每组8只。光镜下观察各组大鼠肺组织的病理改变,测定肺组织湿干重比值（W／D）和支气管肺泡灌洗液（BALF）中总蛋白含量（TP）。采用ELISA法检测肺组织AngU含量,免疫组织化学法（SABC）测定大鼠肺组织Cav-1的表达水平。结果H—VT组大鼠肺组织病理损伤程度,肺组织W／D比值、BALF中TP含量和肺组织AngⅡ含量均明显高于对照组和CAP组（均P〈0．01）,CAP组和对照组相比较,除AngⅡ含量差异无统计学意义外（P〉0．05）,其余指标均增高（均P〈0．01）;H—VT组大鼠肺组织Cav-1表达水平明显低于对照组和CAP组（均P〈0．01）,且CAP组该指标明显低于对照组（P〈0．01）;各组大鼠肺组织Cav-1与AngⅡ含量之间呈负相关（r=-0．821,P〈0．01）。结论大潮气量机械通气通过诱导大鼠肺组织AngⅡ高表达导致Cav-1表达水平降低,可能是呼吸机所致肺损伤（VILI）发病的重要因素之-。卡托普利可通过抑制肺组织AngⅡ生成,上调Car-1表达水平,对VILI起一定保护作用。     

Mucosal secretory IgA and secretory piece in adult coeliac disease

Immunofluorescence studies with specific antisera to secretory IgA (11S IgA) and secretory piece were carried out on the jejunal mucosa of nine patients with adult coeliac disease (treated and untreated). The results were compared with those obtained in four normal patients and in four patients with local and systemic IgA (7S) deficiency. 11S IgA and secretory piece were localized to the upper third of the epithelial cells of both surface and glandular epithelium in all groups of patients. However, in the untreated coeliac patients fluorescence was also demonstrated in the basement membrane and connective tissue of the mucosa (returning to normal on treatment).On the basis of our findings, a revised pathway for the normal production of 11S IgA is proposed as well as an additional pathway involving a ;backflow' of 11S IgA into the lamina propria in pathological states such as coeliac disease. This backflow is reversed by an adequate gluten-free diet. It is suggested that 7S IgA and 11S IgA may be involved in immune reactions in the mucosa with antigens such as gluten.     

Platelet secretory mechanisms

Platelet granule secretion or exocytosis is required for normal platelet function and plays an important role in the pathogenesis of cardiovascular diseases. Platelets secrete molecules that amplify thrombosis, induce vascular remodeling, recruit and activate cells. The platelet secretory process begins in megakaryocytes where molecules are targeted to developing granules through specific vesicle trafficking and transporter mechanisms. Secretory granules may continue to mature in the circulation after the platelet has been released from the megakaryocyte. The platelet secretory process culminates when ligands interact with specific platelet receptors to trigger exocytosis. A convergence of new insights from several different organisms has begun to illuminate the molecular mechanisms responsible for the platelet secretory process, from granule development through membrane fusion and exocytosis.     

Mucosal secretory reflexes

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Gonadotropin secretory abnormalities

Normal physiology of puberty and normal GnRH, LH, FSH, and hCG secretion have been reviewed. Systemic disorders can affect the neuroendocrine axis and cause varying degrees of hypogonadism by acting at different levels in the axis. As both hypothalamic abnormalities and intrinsic pituitary abnormalities can cause an abnormal FSH/LH response to GnRH, this test does not distinguish hypothalamic from pituitary mechanisms of hypogonadism. Therefore, only in disorders that have been demonstrated to have a structural pituitary abnormality (e.g., iron or granulomatous infiltration of the gonadotrophs) can we be certain that the disorder has its effect at the level of the pituitary. Abnormalities leading to hypersecretion (both ectopic and eutopic) of gonadotropins have also been described. To date, ectopic production of FSH and LH has not been unequivocally demonstrated. Systemic disorders cause mainly hypogonadism, many of the symptoms of which are reversible with control or cure of the disease. The effect of hypersecretion of gonadotropins on the reproductive system depends on the age at which the tumor (ectopic/eutopic) occurs.     

Serum secretory component level in myeloma patients with disorders of the secretory surface

Secretory component (SC) in myeloma serum was measured by a double antibody radioimmunoassay. It was elevated in patients with IgA myeloma and the highest level was observed in a patient with macroglobulinemia. The presence of disorders of secretory surface in myeloma patients slightly but not significantly elevated the serum SC concentration. A significant correlation between serum SC and IgG is demonstrated, but not between serum SC and IgA. Over the whole patient groups, serum SC is significantly related to serum IgM but not when patients with macroglobulinemia are excluded from the calculation. Serum SC is present as SC-IgM in macroglobulinemia and SC-IgM and SC-IgA in IgA myeloma.     

The insulin secretory granule

Summary The insulin secretory granule of the pancreatic B cell is a complex intracellular organelle comprised of a many proteins with different catalytic activities and messenger functions. With the advent of tumour models of the B cells and the application of immunological and molecular cloning techniques considerable progress has been made in recent years towards the elucidation of the structure and function of these granule proteins. A number of examples are selected here for review. Particular emphasis given to how the activities of quite different granule proteins are interdependent and how this contributes to the co-ordination and integration of the organelle's biological functions.This paper is based upon the text of the 24th Minkowski lecture of the European Association for the Study of Diabetes, delivered at its annual meeting in Paris, September 1988     

N-Glycans on secretory component

Human beings live in symbiosis with billions of microorganisms colonizing mucosal surfaces. The understanding of the mechanisms underlying this fine-tuned intestinal balance has made significant processes during the last decades. We have recently demonstrated that the interaction of SIgA with Gram-positive bacteria is essentially based on Fab-independent, glycan-mediated recognition. Results obtained using mouse hybridoma- and colostrum-derived secretory IgA (SIgA) consistently show that N-glycans present on secretory component (SC) play a crucial role in the process. Natural coating may involve specific Gram-positive cell wall components, which may explain selective recognition at the molecular level. More widely, the existence of these complexes is involved in the modulation of intestinal epithelial cell (IEC) responses in vitro and the formation of intestinal biofilms. Thus, SIgA may act as one of the pillars in homeostatic maintenance of the microbiota in the gut, adding yet another facet to its multiple roles in the mucosal environment.     

Regulation of airway secretory cells

Inhaled particles are cleared from the airways by ciliary transport of a discontinuous mucous layer. The effectiveness of this process depends on the viscoelastic properties of the secretion, which in turn depend on the composition and interaction of the glycoprotein constituents. In human airways, two major cell types in the surface epithelium (goblet and ciliated) and two in the submucosal glands (serous and mucous) are known to contain mucin- and/or serum-type glycoproteins. This article summarizes current knowledge regarding the secretable products of each of these cell types and the conditions under which they are released into the airway lumen.