中药抗内毒素损伤血管内皮细胞的作用

内毒素对血管内皮细胞的损伤是多种疾病包括大肠杆菌病致病的根本原因,能介导多种细胞,特别是激活单核巨噬细胞,使其合成和释放各种细胞因子,再通过旁分泌或体循环作用于其它组织细胞,引起全身炎症反应综合征,严重者导致休克、多器官功能衰竭和死亡.虽然现在预防和治疗内毒素损伤的方法和途径多种多样,但还没有一种非常有效的手段.而作为天然物品的中药,有很多种类可以抗内毒素损伤,并且具有低毒低副作用等优点,有可能成为今后防治内毒素损伤的重要研究方向.     

从微血管内皮细胞角度用中药防治猪大肠杆菌病的新思路

猪大肠杆菌病一直是严重危害畜牧业的一大疫病，使用大量扰生素防治此病,给畜牧生产和人类健康带来很多危害，并造成环境污染，因而寻找能够替代扰生素的天然药物迫在眉睫。由于中药在治疗疾病方面有诸多优势,备受世人关注。但由于缺乏新的研究方法和指导思想,中药的应用一直止步不前。笔者试图从微血管内皮细胞角度防治大肠杆菌病,即通过改善微循环和保护内皮细胞的途径来防治内毒素性体克,为进一步治疗疾病提供一种新的思路。     

内毒素诱发的麻醉小马血液理化值变化时使用氟胺烟酸葡胺的效果

埃希氏大肠杆菌内毒素休克期间,在血像和血液化学值发生许多变化的同时,血液动力学也发生改变。马属动物中,血糖体内平衡紊乱、高胰岛素血症、粒细胞减少、弥慢性血管内凝血,以及如组织酶的血浆浓度所显示的细胞损伤加重等都是与内毒素引起的休克以及胃肠功能失调相关联的常见并发症。     

SLT-2e对大鼠肠黏膜微血管内皮细胞分泌PG12、TXA2和PAF的影响

志贺样毒素Ⅱ型变异体（SL T-2e）又叫猪水肿病毒素，能引起仔猪水肿病，是仔猪水肿病的主要毒力因子。SLT-2e作用于微血管能引起微血管内皮细胞损害而导致水肿，因此在猪水肿病的发生中起着决定性作用。Methiyapun等研究表明水肿病大肠杆菌对猪肠黏膜没有重要的病理变化，而靶细胞是微血管内皮细胞，表现为内皮细胞空泡化、血管周围水肿、微血栓形成等。     

闽西地区猪源大肠杆菌O157∶H7的分离与鉴定

大肠杆菌 ( E.coli O157)是一种新型的致病性大肠杆菌 ,能引起人类出血性腹泻和溶血性尿毒综合征 ,该菌无侵袭力 ,也不产生肠毒素 ,但能产生一种毒力甚强的细胞毒素 ,引起盲肠、阑尾和升结肠黏膜上皮细胞坏死、黏膜充血、水肿和出血 ,还可进入血液 ,并通过血脑屏障 ,损伤血管内皮细胞而引起血栓性微血管病。病变部位主要在肾脏时可导致溶血尿毒综合征 ,也可引起肠壁梗死、出血 ,以及中枢神经系统病变。本病最早于 1 982年在美国首次暴发 ,之后加拿大、英国和日本等发达国家 ,都发生过大肠杆菌 O157的暴发流行 ;尤其是 1 996年日本暴发近万…     

禽大肠杆菌内毒素对蛋鸡致病作用的病理学研究

将鸡源致病性大肠杆菌悬液反复冻融，提取粗制细菌内毒素．以静脉注射和腹腔注射途径接种于产蛋鸡。结果证明，鸡大肠杆菌内毒素可引起产蛋鸡急性死亡，病理变化以出血性坏死和弥散性血管内凝血为特征．     

产蛋鸡实验性卵巢炎—腹膜炎的病理学研究

产蛋鸡经静脉、腹腔、肌肉、皮下、气囊、气管、口服、口服与气管内联合以及泄殖腔等９种途径实验感染鸡源致病性大肠杆菌，证明鸡大肠杆菌病主要经呼吸道感染，引起以嗜异性粒细胞渗出和浸润为主的急性炎症，经泄殖腔感染不成功；经静脉和腹腔接种其粗制内毒素则可引起急性死亡，以出血性坏死和弥散性血管内凝血为特征。电镜观察发现，经改良马丁肉汤３７℃培养７２ｈ，感染菌菌毛生长良好，并有大量大肠杆菌粘附和克隆在鸡胚气管粘膜上皮细胞纤毛表面，而３７℃２４ｈ的相同培养物中却几乎没有菌毛表达和细菌粘附。本研究结果表明，鸡源致病性大肠杆菌借助其菌毛经呼吸道入侵，在局部生长繁殖，病菌本身及其裂解释放的内毒素对产蛋高峰期的鸡卵巢有强致病作用，引起卵巢炎、卵黄性腹膜炎以及化脓和坏死。     

禽大肠杆菌内毒素对蛋鸡致病作用的病理学研究

将鸡源致病性大肠杆菌悬液反复冻融，提取粗制细菌内毒素，以静脉注射和腥腔注射途径接种于产蛋鸡，结果证明，鸡大肠杆菌内毒素可引起产蛋鸡急性死亡，病理变化以出血性坏死和弥散性血管内凝血为特征。     

兔脑炎原虫引起脑细胞凋亡与血脑屏障破坏的关系

为了研究兔脑炎原虫如何破坏血脑屏障,侵入脑组织并引起脑肉芽肿形成,本试验采用IG染色、MGP染色,TUNEL染色和anti-GFAP染色等方法对26只有典型脑炎原虫病神经症状的病兔和10只健康兔的脑组织进行了详细研究。结果显示:病兔大脑皮质有少部分锥体细胞、血管内皮细胞及星形胶质细胞发生不同程度的凋亡。病损的血管旁有时检出兔脑炎原虫集落,附近的脑组织有巨噬细胞和小胶质细胞聚集形成的细胞性肉芽肿。用特殊染色可在血管内皮细胞、单核细胞和巨噬细胞中检出大量脑炎原虫和集虫泡。大量星形胶质细胞在病损的脑组织部位增生,包绕在聚集的巨噬细胞和小胶质细胞周围形成了肉芽肿。其粗大的足突在血管周围形成了厚层血脑屏障。总之,兔脑炎原虫通过导致血管内皮细胞和星形胶质细胞凋亡的方式而破坏了血脑屏障;通过侵入血管内皮细胞和单核细胞的方式进入脑组织,引起脑损伤。     

从微血管内皮细胞角度研究用中药防治鸡大肠杆菌病

主要通过从鸡大肠杆菌病的研究现状、与微血管内皮细胞之间的关系、中药对鸡大肠杆菌病的防治等方面阐述中药在治疗鸡大肠杆菌病过程中所具有的独特优势。     

百草圣注射液抗感染作用的试验研究

将大肠杆菌注入小鼠的膀胱后观察药物对细菌上行感染肾脏的抑制作用；家兔静脉注射大肠杆菌内毒素后观察药物对细菌内毒素引起机体发热的影响；采用大鼠足趾类性肿胀模型观察药物对炎性肿胀及机械压迫足趾疼痛的抑制作用。结果百草圣注射液治疗动物感染性疾病的作用机制主要与其清除体内细菌感染和减轻发热，肿胀，疼痛等炎症反应有关。     

Staphylococcus aureus lipotechoic acid induces differential expression of bovine serum amyloid A3 (SAA3) by mammary epithelial cells: Implications for early diagnosis of mastitis

Mastitis is one of the most costly diseases of agriculturally important animals and is a common problem for lactating cows. Current methods used to detect clinical and especially subclinical mastitis are either inadequate or problematic. Pathogens such as the gram-positive bacterium Staphylococcus aureus or the gram-negative bacterium Escherichia coli typically cause mastitis. E. coli induces clinical mastitis, whereas, S. aureus causes a subclinical, chronic infection of the mammary gland. In this study we report the differential expression and secretion of mammary-derived serum amyloid A3 (SAA3) by bovine mammary epithelial cells following stimulation with the S. aureus cell wall component, lipotechoic acid (LTA). Two-dimensional immunoblot analyses confirmed that bovine SAA3 is the predominant SAA isoform produced by LTA stimulated mammary epithelial cells. Our previous study showed that bovine SAA3 is also differentially expressed in response to the gram-negative bacterial endotoxin lipopolysaccharide. Collectively, these data indicate that the local production of SAA3 by mammary epithelial cells in response to either gram-positive or gram-negative bacterial components may provide a sensitive indicator for early detection and treatment of mastitis in vivo, minimizing chronic cases of infection, the spread of mastitis to other animals, and economic losses.     

Effect of Pasteurella haemolytica-derived endotoxin on pulmonary structure and function in calves

The role of endotoxin in the pathogenesis of acute pneumonic pasteurellosis is uncertain. Recently, we reported that Escherichia coli-derived endotoxin given by airway inoculation fails to induce lung injury in calves. Because Pasteurella haemolytica-derived endotoxin may differ substantially from E coli in its pathogenicity, we repeated these studies with Pasteurella endotoxin. Intratracheal inoculation of P haemolytica endotoxin caused hypoxemia and increased the alveolar-arterial oxygen differences without causing hypercarbia or changes in lung mechanical properties and volumes. In contrast, IV inoculation of endotoxin caused systemic hypotension, leukopenia, gas exchange impairment, increased total pulmonary resistance, and decreased dynamic compliance. Both routes of inoculation increased serum endotoxin concentrations and were associated with areas of pulmonary hemorrhage, edema, and acute inflammation. We concluded that P haemolytica-derived endotoxin is pathogenic by IV and airway routes of inoculation, and therefore differs from E coli endotoxin in its ability to induce lung lesions in calves.     

用小鼠模型模拟仔猪腹泻的可行性探索

仔猪腹泻给养猪业造成了很大的经济损失,若能用模式动物模拟这一现象,可以更好地研究其遗传机理,以便为抗病育种提供理论依据。本研究以模式动物-小鼠为实验动物,进行大肠杆菌F4和F18毒株腹腔注射攻毒实验和细菌与小肠黏膜上皮细胞的粘附实验。结果表明:虽然攻毒后的小鼠有腹泻现象,但在体外黏附实验中未观察到细菌和小鼠小肠黏膜上皮细胞的粘附发生,说明腹腔注射攻毒条件下小鼠细菌性腹泻的发生机理不是由于细菌和小鼠小肠黏膜上皮细胞的粘附所导致的,与仔猪大肠杆菌性腹泻的发生机理不同,因而用腹腔注射攻毒小鼠来模拟仔猪细菌性腹泻是不可行的。     

中兽药防治大肠杆菌性仔猪腹泻研究

仔猪腹泻是严重的仔猪疾病之一,常用抗生素进行治疗,但细菌耐药性导致药物的治疗效果下降。目前,有很多研究报道中草药防治仔猪腹泻取得了良好的疗效。本文从中药抗动物腹泻的作用机理、仔猪大肠杆菌性腹泻的中兽医辨证、中药抗仔猪大肠杆菌性腹泻的作用机理三个方面展开论述中药防治仔猪腹泻的研究进展,为防治仔猪腹泻的中兽药开发提供理论基础。     

Flunixin meglumine attenuation of endotoxin-induced damage to the cardiopulmonary vascular endothelium of the pony

Endotoxic shock was induced in 5 ponies by intraperitoneal injections of 20, 40, 60, 80, and 80 micrograms of Escherichia coli endotoxin (LPS)/kg of body weight at 0, 6, 12, 18, and 24 hours, respectively. At 24 hours, the ponies also were given 20 micrograms of LPS/kg via catheter in the left ventricle of the heart. A 2nd group of 4 ponies was given 1.1 mg of flunixin meglumine (FM)/kg, IV, at 6, 12, 18, and 24 hours just before the corresponding LPS injection. Two hours after the 24-hour LPS injection, the ponies in both groups were anesthetized, the lungs were perfused with fixative, and portions of the pulmonary arteries and veins and right and left ventricles were prepared for scanning and transmission electron microscopy. In ponies that were given only LPS, some areas of pulmonary vascular endothelium appeared normal when compared with untreated controls, but other areas had disoriented endothelial cells or had varying amounts of sloughing, which ranged from focal areas of a few cells to large areas of denuded endothelium. Ponies treated with FM before LPS had less severe and less extensive endothelial cell damage. In both groups, leukocytes were attached to areas of the vessel wall; endothelial cell damage was greater in these regions. Administration of FM before LPS administration attenuated the LPS-induced endothelial cell damage.     

Comparison of pathophysiologic changes in the lungs of calves challenge exposed with Escherichia coli-derived endotoxin and Pasteurella haemolytica, alone or in combination

Pulmonary responses to intratracheal challenge exposure with Pasteurella haemolytica, with or without Escherichia coli-derived endotoxin, E coli endotoxin alone, or saline solution were compared in anesthetized, mechanically ventilated neonatal calves. Baseline values for dynamic compliance, total pulmonary resistance, functional residual capacity, arterial blood gas tensions, hemogram, leukogram, and systemic and pulmonary arterial pressures were recorded for each calf. After baseline data were obtained, calves were challenge exposed with logarithmic-growth phase P haemolytica organisms with or without E coli endotoxin, E coli endotoxin alone, or saline solution (0.9% NaCl). Physiologic data were obtained immediately after challenge exposure and at various intervals over the next 6 hours. Calves challenge exposed with P haemolytica alone developed sever hypoxemia, had increased alveolar-arterial oxygen difference and threefold increases in total pulmonary resistance, became hypercarbic, had decreased functional residual capacity, and developed systemic hypotension without change in pulmonary arterial pressure. At necropsy, these calves had extensive multifocal areas of necrohemorrhagic and purulent pneumonia. Ratio of extravascular lung water to lung dry weight was not significantly increased in lung specimens obtained from calves challenge exposed with P haemolytica, but ratio of lung wet weight to dry weight was increased, indicating that increased lung wet weight was attributable largely to increased solids and not to fluid alone. (Extravascular lung water measurement excludes fluid from the vascular compartment.) Intratracheal challenge exposure with endotoxin failed to alter lung function and caused minor changes in lung structure consisting of focal areas of hemorrhage and edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apoptosis of bovine neutrophils during mastitis experimentally induced with Escherichia coli or endotoxin

OBJECTIVE: To determine whether apoptosis of neutrophils was accelerated during mastits experimentally induced by use of Escherichia coli or E coli endotoxin and whether differences were apparent in the response to E coli or endotoxin. ANIMALS: 11 healthy lactating Holstein cows. PROCEDURE: Blood samples were collected from cows at various intervals after intramammary inoculation with E coli or endotoxin. Percentage of apoptotic neutrophils detected after in vitro incubation for 3 hours was determined. Fluorescein isothiocyanate-labeled annexin-V in combination with propidium iodide was used to distinguish apoptosis and necrosis of neutrophils. Total and differential circulating leukocyte counts and rectal temperature were determined at the time of collection of blood samples. Milk yield and milk somatic cell counts were determined at the time of milking. RESULTS: Inoculation of endotoxin did not accelerate in vitro induction of neutrophil apoptosis. However, inoculation of E coli increased the percentage of apoptotic neutrophils. At 18 hours after inoculation, 20% of the neutrophils were apoptotic, compared with 5% before inoculation. Milk somatic cell count and rectal temperature increased, milk production and total leukocyte count decreased, and percentage of immature neutrophils increased after inoculation with E coli or endotoxin. However, kinetics of the responses were more rapid, more severe, and of shorter duration during endotoxin-induced mastitis. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro induction of apoptosis of neutrophils was accelerated only during E coli-induced mastitis and not during endotoxin-induced mastitis. Endotoxin inoculation as a model for studying coliform mastitis in dairy cows should be viewed with caution.     

Limulus test--a rapid and simple method for the detection of endotoxins produced by gram-negative bacteria in mastitis milk

According to the present study the limulus amebocyte lysate test (LAL) seems to be a convenient test to detect endotoxin in milk from udder quarters with and without inflammation. The correlation between endotoxin concentration and the results from the bacteriological investigation of 79 milk samples was good (Table I). Determination of endotoxin in 20 milk samples from cases of acute clinical mastitis with high cell count and a negative bacteriological culture showed that all but one had an endotoxin concentration of greater than 1.0 ng/ml milk (Table II). By using a micromethod of the LAL it is possible to detect cases of mastitis caused by gram-negative bacteria about one hour after the sample has reached the laboratory. In a preliminary field study milk from 13 cases of acute clinical mastitis were tested by a modified limulus amebocyte lysate (LAL) test ("cowshed test"). A 100% correlation to bacteriological findings was observed (Table IV). By using the LAL test to detect mastitis cases caused by gram-negative bacteria great economic advantages and less risk for resistance problems can be achieved by using proper antibiotics. This is the fact in Sweden where the frequency of acute clinical mastitis caused by streptococci (100% of strains sensitive for penicillin) and Staphylococcus aureus (about 90% of strains sensitive for penicillin) is high (70-80%) and about 20% are caused by gram-negative bacteria, mostly E. coli.