一氧化氮在哮喘大鼠气道炎症中的作用

为探讨一氧化氮在哮喘大鼠气道炎症中的作用,采用卵白蛋白作为致敏原制备哮喘大鼠模型,用Ｓ—Ｐ免疫组化染色方法对肺组织诱导型一氧化氮合酶ｉＮＯＳ的活性测定及定位分析。结果显示：哮喘大鼠肺组织（ｉＮＯＳ）的表达活性明显高于正常对照组（Ｐ＜０００１）。主要存在于支气管上皮细胞,支气管平滑肌细胞,肺泡上皮,血管内皮和平滑肌细胞,浸润的中性粒细胞和巨噬细胞,而淋巴细胞表达不明显。用甲基强的松龙处理后哮喘大鼠肺组织诱导型一氧化氮合酶表达明显降低。说明一氧化氮在哮喘气道炎症中起重要作用,甲基强的松龙治疗哮喘可以减轻气道炎症,使哮喘大鼠肺组织中诱导型一氧化氮合酶表达降低     

潜艇舱室环境中有害气体对肺组织的慢性损伤

在潜艇舱室复杂的气体环境下,有害气体可能刺激气管上皮细胞并损伤肺血管内皮细胞,引起肺组织慢性炎症反应以及氧化与抗氧化功能失衡。肺组织内氧自由基增多与炎症反应相互作用,引起血液和肺组织中超氧化物歧化酶（superoxide dismutase,SOD）、血管内皮素-1（endothelin-1,ET-1）和一氧化氮含量变化,并产生大量炎性细胞以及肿瘤坏死因子-α（ tumor necrosis factor-α, TNF-α ）、白介素一6（interleukin-6,IL-6）等炎性介质浸润肺组织。这些炎症反应可以导致气管壁的损伤修复过程反复发生,引起气管结构重塑,还可以损伤肺血管,使肺血管平滑肌增生,肺血管阻力增加,形成肺动脉高压,同时,长期炎症反应还可导致肺实质的纤维化,进一步影响肺功能。     

肺动脉高压大鼠肺组织Notch信号的改变

目的探讨肺动脉高压（pulmonary hypertension，PH）大鼠肺组织Notch受体的改变。方法构建肺切除＋野百合碱PH大鼠模型，与正常大鼠比较肺血管重构指标的改变。进行肺组织免疫组化Notch 1-Notch4受体染色和实时荧光定量PCR（RT—PCR）检测（Notch 1-Notch4）mRNA。结果肺切除＋野百合碱组大鼠平均肺动脉压力（mPAP）、右心指数[fulton index，RV／（LV＋S）]、肺小动脉中膜厚度百分比（WT，％）、非肌性小动脉肌化程度、管壁细胞增殖度，明显高于正常大鼠，差异有显著意义（P〈0．05），有新生内膜形成。肺组织免疫组织化染色，肺切除＋野百合碱组和正常对照组大鼠肺动脉均有Notch1，Notch3，Notch4受体表达，未见Notch2受体表达。Notch1表达于血管内皮细胞和平滑肌细胞，Notch3主要表达于平滑肌细胞，Notch4主要表达于内皮细胞。肺切除＋野百合碱组肺组织（Notch1～Notch4）mRNA水平高于正常对照组。结论Notch1，Notch3，Notch4表达于肺动脉，随着PH肺血管重构的发生，表达上调。Notch信号很可能参与了PH肺血管重构过程。     

缺氧性肺动脉高压大鼠肺组织面积密度变化及其机制的研究

目的　研究缺氧性肺动脉高压 (HPH)肺组织面积密度变化及其机制。方法　模拟海拔5km高原连续缺氧 ,制备HPH大鼠动物模型 ,用图像分析、光镜、电镜、组织化学等方法分析、观察缺氧后 10、2 0、30d和平原对照组肺组织面积密度及形态学变化。结果　缺氧后大鼠肺组织面积密度明显增加 ,以 2 0d和 30d为著 ,缺氧 10d时为 2 7.0 8%± 1.2 9%、2 0d时为 31.33%± 0 .72 %、30d时为31.10 %± 1.95 % ,与对照组 ( 2 2 .78%± 1.17% )比较 ,差异均有显著性 (P <0 .0 5 ,P <0 .0 1)。缺氧 2 0d时与 10d比较 ,差异有显著性 (P <0 .0 5 ) ,缺氧 30d与 10d比较 ,差异无显著性 ,但其P值 ( 0 .0 5 7)接近显著性水平。大鼠Ⅱ型肺泡上皮细胞 (PⅡ )不同程度肿胀、退变 ,板层体减少或空化 ;肺泡腔表面活性物质 (PS)呈泡沫状。各级小动脉管壁增厚 ;毛细血管内中性粒细胞滞留、嵌塞 ,血小板聚集 ;内皮细胞肿胀 ,基底膜增厚。结论　缺氧可引起大鼠肺组织面积密度增加 ,肺泡有效气体交换面积减少。其变化与PⅡ和PS系统受损所致的肺萎陷、肺血管结构重塑、肺泡腔有形成分增加有关     

博莱霉素致大鼠肺纤维化及与肺血管内皮细胞损伤的关系

目的 探讨血管内皮损伤与博莱霉素(BLM)致大鼠肺纤维化发生间的关系。方法 实验组大鼠经气管灌注BLM制作肺纤维化模型,采用免疫组化及图像分析系统对其肺组织中血管内皮细胞生长因子(VEGF)进行定性、定量分析。结果 (1)组织学观察:染BLM后3、7 d,大鼠肺泡腔及间隔水肿,炎细胞渗出,肺泡Ⅰ型及Ⅱ型上皮细胞变性、坏死,肺泡上皮细胞基底膜断裂,血管内皮细胞肿胀,核浓缩;7、14 d,大鼠肺泡Ⅱ型上皮细胞增生,肺泡间隔有较多成纤维细胞及新生毛细血管形成;28 d,大鼠肺泡间隔增厚,肺泡结构破坏,肺组织明显纤维化样改变。(2)VEGF免疫组化染色:对照组大鼠肺组织呈弱表达,主要分布于肺泡Ⅱ型上皮细胞、支气管黏膜上皮细胞、肺泡巨噬细胞及肺间质细胞。染BLM组大鼠VEGF呈明显高表达,其中,3 d至28 d,大鼠肺泡Ⅱ型上皮细胞VEGF持续高表达,表达量明显高于对照组,差异有统计学意义(P<0.05,P<0.01);7、14、28 d,大鼠肺间质细胞VEGF呈高表达;3 d至28 d,大鼠肺泡巨噬细胞VEGF表达均升高,与对照组的差异均有统计学意义(P<0.05,P<0.01)。结论 VEGF持续高表达与大鼠血管内皮细胞损伤有关,而血管内皮细胞的损伤可能是BLM诱发大鼠肺纤维化的重要启动因素之一。     

辛伐他汀对血小板源生长因子诱导的肺血管平滑肌细胞内粘着斑及肌动蛋白细胞骨架组装的影响及意义

目的观察辛伐他汀（simvastatin）对血小板源生长因子（platelet—derived growth factor—BB，PDGF—BB）诱导的增殖细胞内粘着斑（focal adhesion，FA）蛋白及肌动蛋白细胞骨架动态组装的影响，旨在探讨辛伐他汀抑制血管平滑肌细胞（vascular smooth muscle cell，VSMC）增殖和迁移与细胞骨架变化的关系。方法以体外培养的SD大鼠血管平滑肌细胞为基础，[^3H]—TdR掺入量测定DNA合成，透射电镜观察细胞的表型状态，采用免疫细胞化学和荧光细胞化学法，观察辛伐他汀对血小板源生长因子诱导的肺血管平滑肌细胞增殖细胞内粘着斑蛋白及肌动蛋白细胞骨架组装的影响。结果血小板源生长因子受刺激后（对照组），血管平滑肌细胞[^3H]-TdR掺入量明显增加，电镜示细胞超微结构出现表型变化，血管平滑肌细胞中增殖细胞内粘着斑蛋白中的桩蛋白（paxillin）体积增大、数量增加，血管平滑肌细胞内F—actin数量明显增加，呈纵向平行排列，α—SM—actin体积缩小、数量减少。辛伐他汀可明显抑制这些生物学效应（药物干预组）。结论辛伐他汀可以抑制血小板源生长因子介导的血管平滑肌细胞内增殖细胞内粘着斑蛋白中的桩蛋白，F—actin，α-SM-actin的动态组装，进而发挥抑制血管平滑肌细胞增殖和迁移的能力。     

大鼠实验性矽肺早期生长反应基因表达及其作用的初步探讨

目的　探讨核转录因子早期生长反应基因 (Egr 1)在矽肺发生发展中的作用。方法　建立大鼠矽肺模型 ,用免疫组化SP法结合图像分析技术观察了大鼠矽肺组织中各种细胞表达Egr 1、转化生长因子 β1(TGF β1)和纤维黏连蛋白 (FN)的动态变化及相互关系。结果　大鼠矽肺组织中肺巨噬细胞、肺泡上皮细胞、支气管上皮细胞、间质细胞的Egr 1表达 (灰度值范围 118.58± 5.65～ 168.52± 5.67)比对照组 (灰度值范围 166.2 3± 5.2 3～ 188.12± 8.3 5)均明显增强 ,且主要定位于胞核 ;这 4种细胞表达TGF β1(灰度值范围 12 3 .49± 5.65～ 170 .2 4± 3 .56)比对照组 (灰度值范围 166.53± 6.2 5～ 198.56± 4.53 )也明显增强 ,且定位于胞浆。在大鼠支气管上皮细胞、肺巨噬细胞、肺泡上皮细胞中FN表达较弱 (灰度值范围150 .3 2± 6.54～ 2 0 1.54± 7.3 8) ,但间质细胞中呈高表达 (灰度值范围 12 1.43± 5.65～ 167.55± 6.3 5)。实验第 1～ 2 8天 ,TGF β1和Egr 1在大鼠支气管上皮细胞、肺巨噬细胞、肺泡上皮细胞和间质细胞表达变化基本同步 ,二者呈正相关 (r =0 .61,P <0 .0 1) ;而FN在上述细胞中表达和Egr 1未见相关性 ;FN与TGF β1在间质细胞中表达呈正相关 (r=0 .46,P <0 .0 1)。结论　SiO2 可上调肺内多种细胞E     

Insulin and atherogenesis

A number of processes are involved in the pathogenesis of atherosclerosis. These include an injury to the endothelial cell barrier of the inner lining of the artery, infiltration of the artery by lipid filled monocyte-macrophages, proliferation of smooth muscle cells, synthesis of connective tissue and thrombus formation. Insulin may be involved in several of these processes. Over 40 years ago it was shown that insulin is necessary for the production of experimental atherosclerosis in cholesterol fed, alloxan diabetic rabbits. Insulin inhibits regression and stimulates formation of lipid containing lesions in a number of species, and can promote lesions in animals fed normal diets. Insulin is also related to lipid metabolism in the artery wall and interacts with blood pressure to stimulate lipid synthesis in arteries. Arterial smooth muscle cells cultured from a number of species including humans proliferate in response to levels of insulin similar to those found in normal human physiology. The proliferative effects of insulin are mediated by the insulin-like growth factor receptor and hence may not be impaired in states of insulin resistance. Insulin also stimulates arterial smooth muscle cell migration. Insulin stimulates cholesterol synthesis in cultured smooth muscle cells and enhances LDL receptor activity in a number of cell types. Insulin stimulates connective tissue synthesis, and promotes clotting.Corresponding author     

Cytokinetic and morphological changes in the lungs and lung-associated lymph nodes of rats after inhalation of fly ash

Fischer-344 rats (male and female) were exposed to 36 mg/m³ of fluidized bed coal combustion fly ash or sham-exposed for 7 hr/day, 5 days/week for 4 weeks, and sacrificed after 2 or 4 weeks of exposure and at 2, 22, and 42 weeks after the end of exposure. Animals were injected with tritiated thymidine 2 hr before sacrifice and autoradiographs prepared from 1-μm sections of lung and lymph node tissue embedded in glycol methacrylate plastic. Differences in labeling indices of pulmonary epithelial cells, alveolar macrophages, airway epithelial cells, and cells of the lung-associated lymph nodes between the exposed and control animals were maximal after 2 and 4 weeks of exposure. Labeling indices for lung epithelial cells were about the same in control and exposed animals at 2, 22, and 42 weeks after the end of exposure. However, these values were elevated relative to earlier control levels. In contrast, morphological changes in the fly ash-exposed animals were most prominent after the end of the exposure. These changes included thickening of the alveolar walls, clusters of particle-filled macrophages in the alveolar region, and perivascular inflammation. Additionally, there were small granulomas in the alveolar region at 42 weeks after the end of exposure. Granulomas were also formed in the lung-associated lymph nodes and bronchus-associated lymphoid tissue. We conclude that the inhalation of fly ash alone had little detrimental effect upon the rat lung. However, the increases in proliferation indicate the potential for fly ash combined with a carcinogen to enhance the carcinogen's effect.     

Nonneoplastic effects of vinyl chloride in mouse lung

In a previous study, a high incidence of pulmonary tumors (alveologenic neoplasia in mouse lung exposed to vinyl chloride at heavy dose (2500 and 6000 ppm) for long durations (5 and 6 months) was reported (Y. Suzuki, 1978, Environ. Res.16, 285–301). In the present study, nonneoplastic effects in mouse lung were investigated by light and electron microscopy. As major light microscopic alterations, proliferation and hypertrophy of the terminal bronchiolar cells, consisting of ciliated and Clara cells, hypersecretion of the epithelial mucin in the goblet cells of both the bronchial and the proximal bronchiolar epithelium, hyperplasia of alveolar epithelium, mobilization of alveolar macrophages, and occasional presence of peribronchial or bronchiolar chronic inflammation, were observed. Electron microscopically, Clara cells of the terminal bronchiolar epithelium showed proliferation of the rough and smooth surfaced endoplasmic reticulum and appearance of large and abnormally shaped mitochondria. Similar alterations were found in the ciliated cells. Submicroscopic changes of pulmonary alveoli were represented by focal thickening of the basement membrane, multiple foci of hyperplastic type II cell (the precondition of the alveologenic tumor), active discharge of osmiophilic lamellar bodies from the type II cell and phagocytosis of the bodies by macrophages, appearance of cholesterol crystalloids in the macrophages, degeneration of alveolar septal cells and occasional appearance of a large nucleus with swelling of the capillary endothelium.     

同型半胱氨酸促进血管平滑肌细胞增生的实验研究

目的 :　研究同型半胱氨酸 (homocysteine,Hcy)是否促进平滑肌细胞增生。方法 :　SD大鼠主动脉平滑肌细胞体外培养 ,随机分为 5组 :1 .正常对照组 ,2 .1 .0 mmol/L Hcy组 ,3 .2 .5 mmol/L Hcy组 ,4.5 .0 mmol/L Hcy组 ,5 .1 0 .0 mmol/L Hcy组。培养 72 h后 ,采用细胞毒试验、流式细胞仪检测细胞生长情况。 2 0只 SD大鼠进行体内观察 ,随机分为高蛋氨酸组 (M组 )和对照组 (C组 ) ,M组每日给予含蛋氨酸 3 %的饮食 ,在 1 2 w进行主动脉病理学光镜和电镜检查。结果 :　 1 .细胞毒试验观察到 Hcy促进平滑肌细胞生长与增殖 ;2 .流式细胞仪检测可见 Hcy促进平滑肌细胞由 G1期进入合成的 S期 ;3 .在 4w时 ,高蛋氨酸组大鼠即出现高同型半胱氨酸血症 ,高蛋氨酸血症 ;4.病理检查光镜下可见高蛋氨酸组大鼠主动脉有明显中膜增厚 ,平滑肌细胞增生 ;5 .电镜检查可见平滑肌细胞肿胀 ,内质网扩张 ,线粒体水肿 ,溶酶体增多。结论 :　同型半胱氨酸促进大鼠血管平滑肌细胞增生     

Enhanced expression of angiotensin II type 1 receptor in usual interstitial pneumonia

BACKGROUND: Angiotensin II, a potent vasoconstrictor, has been considered to be involved in various fibrotic disorders including idiopathic interstitial pneumonias. To clarify whether this agent contributes to the development and progression of usual interstitial pneumonia, a major entity of idiopathic interstitial pneumonias, we immunohistochemically examined expression of its specific receptor, angiotensin II type 1 receptor, in human normal and diseased lung tissues. METHODS: Video-assisted thoracoscopic lung biopsy specimens obtained from patients with usual interstitial pneumonia (n=8) were sectioned and stained using single or double immunostaining techniques with specific antibodies against angiotensin II type 1 receptor and smooth muscle actin. Lung tissues of desquamative interstitial pneumonia (n=2) and normal lung tissues (n=6) were also examined for comparative analyses. RESULTS: Expression of angiotensin II type 1 receptor was limited in vascular and bronchial smooth muscle cells in normal lungs. In contrast, the receptor-positive mesenchymal cells, most of which were also positive for smooth muscle actin and arranged like a bundle, were markedly increased in association with dense collagen deposition in thickened alveolar walls of usual interstitial pneumonia. In desquamative interstitial pneumonia, the fibroproliferative change, including angiotensin II type 1 receptor-positive mesenchymal cell proliferation, was milder than that in usual interstitial pneumonia. CONCLUSIONS: These findings suggest that angiotensin II and its type 1 receptor play a profibrogenic role in idiopathic interstitial pneumonias, particularly in usual interstitial pneumonia. Furthermore, angiotensin II type 1 receptor-positive smooth muscle cells increased in diseased lung tissues may be contractile and may contribute to reduction of airspaces in usual interstitial pneumonia.     

被动吸烟致大鼠肺损伤及其对细胞因子的影响

目的 观察长期被动吸烟所致大鼠肺损伤情况及春对体内一氧化氮、白细胞介素－６、８（ＩＬ－６、ＩＬ－８）影响作用如何。方法 采用生化分光光度法测定ＮＯ＾－２／ＮＯ＾－３含量,代表大鼠体内ＮＯ水平。用酶联免疫标记法测定ＩＬ－６、ＩＬ－８含量。结果单纯吸烟组,血清、支气管肺泡灌洗液、肺组织中的ＮＯ含量均明显低于正常对照组。ＩＬ－６、ＩＬ－８含量均高于正常对照组。结论 长期被动吸烟可引成肺组织一定程度的损伤     

葛根素对低氧性肺动脉平滑肌细胞增殖与凋亡及Kv1.5表达的影响

目的 观察葛根素对低氧性肺动脉平滑肌细胞( PASMCs)增殖与凋亡及电压门控型钾离子通道亚型(Kv1.5)表达的影响,探讨葛根素在改善低氧性肺动脉高压与抑制肺血管重建中可能的作用机制.方法 原代培养大鼠PASMCs,随机分为正常对照组(5％CO2常氧),低氧组(5％O2、5％CO2、90％N2三气培养),3个浓度葛根素干预组(在低氧组基础上分别加入终浓度为1×104、1×10-4、1×10-3 mol/L葛根素,37℃培养24 h).采用CCK-8法和流式细胞仪检测细胞增殖情况,分光光度法检测caspase-3活力,蛋白印迹及实时定量聚合酶链反应(PCR)法分别检测Kv1.5蛋白和mRNA表达.结果 与正常对照组(细胞活性:0.940±0.045,S期细胞比例:9.67％±1.28％,Caspase-3活力:0.1073±0.0113,Kv 1.5蛋白:0.886±0.038,Kv 1.5 mRNA 0.0377±0.0031)比较,低氧组细胞活性(1.296±0.034)、S期细胞比例(18.19％±1.19％)升高,Caspase-3活力(0.0664±0.0049)下降,Kv1.5蛋白(0.602±0.064)及mRNA (0.0108±0.0014)表达下降,差异均有统计学意义(P＜0.05);与低氧组比较,各剂量葛根素干预组细胞活性和S期细胞比例下降,Caspase-3活力升高,Kv 1.5蛋白及mRNA表达上调,差异均有统计学意义(P＜0.05).结论 葛根素可抑制低氧性PASMCs增殖,促进其凋亡,其作用机制可能通过上调Kv 1.5表达抑制PASMCs的增殖.     

浅论支气管扩张治疗

支气管扩张是呼吸系统常见的支气管慢性化脓性疾病,是指支气管及其周围肺组织的慢性炎症损坏管壁,引起支气管壁肌肉和弹力支撑组织的破坏,以致支气管不正常扩张和变形。     

浅论支气管扩张治疗

支气管扩张是呼吸系统常见的支气管慢性化脓性疾病,是指支气管及其周围肺组织的慢性炎症损坏管壁,引起支气管壁肌肉和弹力支撑组织的破坏,以致支气管不正常扩张和变形。     

Pulmonary embolization-induced thymus hyperplasia in rabbits

The effects of pulmonary embolization on the thymus glands of rabbits were studied morphologically, morphometrically and immunohistochemically. Pulmonary embolization was induced by an intravenous injection of 0.4 ml of Sephadex bead suspension (particle size; 150 to 300 microns, about 2,000 per ml). Both mean weight and volume of the thymus of rabbits killed at 2 weeks after embolization, were about 1.5 times more than those in control animals treated with physiologic saline. Histological examinations showed enlargement of the cortex and medulla of the thymus, and the embolized Sephadex beads in the branches of pulmonary arteries of the lung. The area ratios of medulla/cortex, in the embolization group and in control, were not significantly different. The cells with immunohistochemically positive staining of anti-nuclear antigen of monoclonal antibody of Ki-67, were found in both portions of the medulla and cortex. These data suggest that pulmonary embolization in the rabbit induces true thymic hyperplasia. An intravenous injection of India ink into the right highest intercostal artery revealed the distribution of bronchial arteries, which send the branches to the right lobe of the thymus. In 2 out of 4 animals killed 2 weeks after pulmonary embolization, the left lobe of the thymus as well as the right were stained with the injected ink. As it is known that pulmonary vascular obstruction caused a marked increase in the bronchial blood flow, these data suggest that the thymus blood supply from the bronchial arteries increases in the conditions of pulmonary embolization, which might contribute to thymus hyperplasia.     

The Role of Obesity-Induced Perivascular Adipose Tissue (PVAT) Dysfunction in Vascular Homeostasis

Perivascular adipose tissue (PVAT) is an additional special type of adipose tissue surrounding blood vessels. Under physiological conditions, PVAT plays a significant role in regulation of vascular tone, intravascular thermoregulation, and vascular smooth muscle cell (VSMC) proliferation. PVAT is responsible for releasing adipocytes-derived relaxing factors (ADRF) and perivascular-derived relaxing factors (PDRF), which have anticontractile properties. Obesity induces increased oxidative stress, an inflammatory state, and hypoxia, which contribute to PVAT dysfunction. The exact mechanism of vascular dysfunction in obesity is still not well clarified; however, there are some pathways such as renin–angiotensin–aldosterone system (RAAS) disorders and PVAT-derived factor dysregulation, which are involved in hypertension and endothelial dysfunction development. Physical activity has a beneficial effect on PVAT function among obese patients by reducing the oxidative stress and inflammatory state. Diet, which is the second most beneficial non-invasive strategy in obesity treatment, may have a positive impact on PVAT-derived factors and may restore the balance in their concentration.     

纳米氧化锌颗粒对大鼠肺及人支气管上皮细胞的毒性作用

目的探讨纳米氧化锌(ZnO)颗粒对大鼠肺及人支气管上皮细胞(HBE)的毒性作用。方法通过病理组织切片,观察不同质量浓度纳米ZnO滴注大鼠气管后其肺组织的病理变化。采用CCK-8法检测不同浓度纳米ZnO对HBE细胞存活率的影响,及流式细胞术检测不同浓度纳米ZnO对HBE细胞内氧化应激活性氧(ROS)、Ca2+浓度以及线粒体膜电位变化的影响。结果染毒后大鼠病理组织切片显示,随着染毒剂量的增加,大鼠肺部的炎性细胞浸润的数量逐渐增多。CCK-8法检测显示:随纳米ZnO染毒剂量的增加,HBE细胞存活率显著降低,HBE细胞内ROS及Ca2+浓度显著增加,线粒体膜电位显著降低(P0.05)。结论 (30±10)nm ZnO颗粒在整体和细胞水平时,可能通过不同机制产生不同种类的ROS,从而对细胞产生氧化损伤及应激效应。     

实验性糖尿病大鼠肺组织晚期糖基化终末产物、肺表面活性物质蛋白质A免疫组织化学分析

目的 探讨实验性糖尿病（diabetes mellitus,DM）大鼠肺组织晚期糖基化终末产物（advanced glycosylated endproducts,AGEs）、肺表面活性物质蛋白质A（surfactant proteins A,SP-A）的变化.方法 48只SD雄性大鼠随机分为DM组和对照组,每组24只.链脲佐菌素（streptozotocin,STZ）60mg/kg尾静脉注射制造DM模型.分别于造模成功后4、12、20周末杀检.免疫组织化学方法 观察肺组织AGEs、SP-A的变化,并进行图像分析（灰度值以0为黑,最大值为白）.结果 （1）AGEs：DM大鼠肺泡上皮细胞、支气管黏膜上皮细胞、血管内皮细胞及平滑肌细胞可见大量AGEs阳性细胞,平均灰度值低于对照组（4周93.92±7.92 vs 104.75±8.20;12周76.25±6.76 vs 93.50±7.56;20周47.63±7.96 vs 142.38±19.76;P均＜0.05）,随着DM病程的增加逐渐降低.（2）SP-A：4周DM大鼠肺泡Ⅱ型细胞、肺泡巨噬细胞、克拉拉细胞可见少量阳性细胞,12、20周可见大量SP-A阳性细胞,平均灰度值均低于对照组（12周75.63±6.70 vs 110.50±13.20;20周47.38±4.84 vs 97.25±9.87;P均＜0.01）.结论 DM大鼠随着病程的增加,出现肺泡Ⅱ型细胞的损伤,可能与AGEs的沉积有关.