重症急性胰腺炎时肠屏障破坏的机制及防治

众多因素参与了重症急性胰腺炎时肠屏障破坏的发生、发展，随之而来的菌群移位及内毒素血症又加重了肠屏障破坏，导致严重不良预后。本文综合了肠屏障受损的可能原因，同时针对发病原因提出了相应防治对策。     

参附注射液对大鼠胰腺移植受体小肠肠粘膜屏障的保护作用

目的探讨参附注射液（SF）对大鼠胰腺移植受体肠粘膜屏障的保护作用及机制。方法24只糖尿病大鼠随机分为缺血再灌注组（IR组。n=12），参附注射液预处理组（SF组．n=12），12只正常大鼠为对照组，IR组和SF组大鼠均接受胰腺移植，再灌注后5d检测小肠通透性和吸收功能，检测血清TNF-α、NO、SOD和淀粉酶活性，取受体空肠粘膜组织检测小肠粘膜粘膜湿重、微绒毛高度及宽度、MDA含量及MPO活性，同时取肠系膜静脉血、肠系膜淋巴结、肝及脾组织进行细菌培养，观察细菌易位情况。结果再灌注后SF组血清TNF—α含量（P〈0．01）、淀粉酶活性（P〈0．01）、MDA含量（P〈0．01）、MPO活性（P〈0．01）、小肠通透性（P〈0．01）、细菌易位率（P〈0．01）和小肠粘膜损伤程度均低于IR组；血清NO和SOD含量、小肠吸收功能均高于IR组（P〈0．01）。结论SF预处理可保护大鼠胰腺移植受体小肠肠粘膜屏障，降低细菌易位率，机制可能与降低胰酶活性、减少TNF—α生成、减轻PMNs粘附与聚集、增加NO和SOD含量有关。     

Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis

OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti-irritative effect of PoCo was evaluated with a visual score and quantified by non-invasive bioengineering methods, namely chromametry and transepidermal water loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient; German pharmacopoeia) were tested in a 4-day repetitive irritation test using SLS. RESULTS: A statistically significant anti-inflammatory activity was observed for PoCo by all three methods when applied in parallel to the induction period of ICD. Application of PoCo after induction of ICD once a day for 5 days, starting just at the end of 4 days, was without any effect. CONCLUSION: An anti-inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by repeated SLS test could be observed and quantified by three independent, non-invasive biophysical assessment parameters. This effect can be explained by its influence on pro-inflammatory enzymes, namely phospholipase A2.     

高血压脑出血患者血肿周围血-脑屏障葡萄糖转运蛋白1表达的研究

目的观察高血压脑出血(ICH)患者血肿周围血-脑屏障葡萄糖转运蛋白1(GLUT1)表达的变化。方法采用免疫组化方法检测28例高血压ICH患者不同病程血肿周围脑组织GLUT1的表达情况。结果与对照组相比,ICH组发病12 h GLUT1表达开始增强,24 h、48 h表达最强(均P<0.01);72 h表达明显下降(P<0.01)。结论ICH早期血肿周围GLUT1表达增多,有助于恢复脑的能量代谢。     

冰片开放血-脑脊液屏障对实验性细菌性脑膜炎治疗影响的研究

目的 探讨冰片开放血-脑脊液屏障（BCB）对实验性细菌性脑膜炎治疗的影响。方法 采用日本大耳白兔作为实验动物，随机分为对照组、冰片组和脑膜炎组。经枕大池注入肺炎球菌悬液建立脑膜炎模型，以冰片作为开放BCB的制剂。以连续静脉注射丙戊酸钠后不同时间点的脑脊液中丙戊酸钠浓度变化作为判断BCB通透性的指标；硝酸镧示踪法观察脑组织表现作为BCB通透性的形态指标。给予脑膜炎动物头孢吡肟或冰片＋头孢吡肟治疗，记录动物存亡情况；取脑脊液（CSF）进行细胞计数及生化检查。取脑组织作常规病理染色，以观察冰片开放BCB对实验性细菌性脑膜炎治疗的影响。结果 给药后对照组CSF中丙戊酸钠浓度基本保持稳定，冰片组CSF中丙戊酸钠浓度于给药后0．5h时即高于对照组并逐渐上升，至6h时达高峰，然后开始下降，14h时浓度仍高于对照组。脑组织超微结构显示，对照组无硝酸镧颗粒通过BCB，脑膜炎组硝酸镧颗粒分布于毛细血管基底膜外，冰片组弥漫性分布于神经细胞间隙和轴突周围。给予头孢吡肟治疗后，脑膜炎＋冰片组动物存活率（9／12，75％）明显高于脑膜炎组（6／18，66．7％）（P〈0．05），但两组间CSF细胞数及蛋白、葡萄糖水平差异无统计学意义。近皮层脑组织HE染色显示，脑膜炎组可见脑组织大量炎症细胞渗出和软化坏死灶,血管“套袖”现象明显，而脑膜炎＋冰片组脑组织内炎症细胞渗出较少，无血管“套袖”现象，无明显坏死软化灶。结论 冰片确实能明显增加BCB的通透性并具有可逆性特点，抗生素联合冰片能改善实验性细菌性脑膜炎治疗效果，为细菌性脑膜炎的治疗提供了新的思路。     

Neutrophilic defensins penetrate the blood-brain barrier

Defensins are small, cationic, cyclic peptides that are abundantly stored in granules of neutrophils. Defensins non-specifically interact with membranes by forming weakly ion-selective pores. Here we demonstrate immunolocalization of defensin-secreting cells in human brain. Defensins, secreted by activated granulocytes, apparently are not prevented by the blood-brain barrier (BBB) from diffusing across cerebral endothelium to penetrate the neuropil for a considerable distance from the granulocyte. This is in contrast to other neutrophil proteins like the granuleassociated enzyme elastase or the cytosolic protein MRP-14, which are strictly localized to the cytoplasm or granules of neutrophils. Thus, defensins, known chemokinetic and chemotactic molecules, display a unique distribution at BBB sites. © 1995 Wiley-Liss, Inc.     

Magnetic resonance imaging of antibody-mediated demyelinating experimental allergic encephalomyelitis

Two models of demyelinating experimental allergic encephalomyelitis (EAE) were studied on Lewis rats in whom the disease was induced by injections of either (i) lentil-lectine binding myelin glycoproteins plus myelin basic protein (MBP)-specific T cells (36 rats), or (ii) myelin/oligodendrocyte glycoprotein-specific monoclonal antibody plus MBP-specific T cells (16 rats). In our 24 control rats, 20 received MBP-specific T cells only, and four received myelin glycoproteins plus purified protein derivative-specific T cells. The extent of the resulting blood-brain barrier (BBB) permeability, vasogenic oedema and/or demyelination was assessed in vivo using magnetic resonance imaging (MRI) techniques. The results show that in both demyelinating EAE models the disease appeared more quickly, progressed very rapidly and was more severe than when induced with a similar number of MBP-specific T cells alone. Almost all animals developed hypercute EAE, with a very high mortality rate. MRI showed a very intense BBB breakdown and vasogenic oedema in all the normally ‘leaky’ areas of the central nervous system, and focal lesions corresponding to plaque formation in the brain stem or spinal cord near the ‘leaky’ areas. During the 40-day observation period, the rare survivors of this hyperacute form of EAE presented a chronic form of EAE with serious sequelae. Our results demonstrate that the synergistic effect observed between MBP-specific T cells and antibodies to myelin glycoproteins, especially to myelin/oligodendrocyte glycoprotein, does not only induced demyelinating lesions and chronic clinical signs, but is further responsible, via the normally ‘leaky areas’, for the fatal increase of the BBB breakdown and vasogenic oedema of which there are ample acute clinical signs.     

Taurine entry into perilymph of the guinea pig

Taurine is a β-aminosulfonic acid and is a ubiquitous amino acid whose role in the cochlea is not well established. In this study, its entry from blood into perilymph was investigated in the guinea pig as animal model. The penetration rate of [³H]taurine (molecular weight 125) into the perilymph of the scala vestibuli was measured 1 and 2 h after the intravenous infusion of [³H]taurine in nephrectomized animals. Results showed a rate of penetration in perilymph related to plasma at 36 ± 4.7% (n = 5) after 1 h and 43 ± 5.6% (n = 5) after 2 h. Compared to the penetration rate of urea (molecular weight 60) and mannitol (molecular weight 186) reported previously in rats, a passive entry of taurine into perilymph through the blood-perilymph barrier is suggested. Received: 30 July 1997 / Accepted: 15 January 1998     

C-terminal tail of β-adrenergic receptors: immunocytochemical localization within astrocytes and their relation to catecholaminergic neurons in N. tractus solitarii and area postrema

β-Adrenergic receptors (βAR) in the medial nuclei of tractus solitarii (m-NTS) and area postrema (AP) may bind to catecholamines released from neurons, whereas only the AP has fenestrated capillaries allowing access to circulating catecholamines. Since varied autonomic responses are seen following βAR activation of the dorsal vagal complex, including the m-NTS and AP, we hypothesized that there might be a cellular basis for varied responses to βAR stimulation that depends pn the differential access to circulating catecholamines. Therefore, we comparatively examined the ultrastructural localization of the βAR in relation to catecholaminergic neurons in these regions. An antibody directed against the C-terminal tail (amino acids 404–418) of hamster β-adrenergic receptor (βAR404) was used in this study. The localization of βAR404 was achieved by the avidin-biotin peroxidase complex (ABC) technique in combination with a pre-embed immunogold labeling method to localize tyrosine hydroxylase (TH), the catecholamine-synthesizing enzyme. Within m-NTS and at subpostremal border, labeling for βAR404 was evident along the intracellular surface of plasma membranes of small, apparently distal, astrocytic processes. Astrocytic processes with βAR404-immunoreactivity formed multiple, thin lamellae around TH-labeled and non-TH neuronal cell bodies and dendrites. βAR404-immunoreactive astrocytes also extended end-feet around blood vessels and surrounded groups of axon terminals that were directly juxtaposed to each other. Some, but not all, of these axons demonstrated TH-immunoreactivity. Fewer βAR404-immunoreactive astrocytes were detected in AP, regardless of their proximity to catecholaminergic processes or blood vessels. The present astrocytic localization of βAR404, together with the earlier, neuronal localization of βAR's third intracellular loop, suggest that the βAR may be substantially different between neurons and astrocytes. The regional difference in the prevalence of βAR404-immunoreactive astrocytes suggests that these receptive sites may either: (i) be preferentially activated by catecholamines released from terminals rather than circulating catecholamines; or (ii) be down-regulated in AP due to blood-born substances, such as catecholamines. The extensive localization of βAR in the border between m-NTS and AP also suggests that catecholaminergic activation of these astrocytes may dictate the degree of diffusion of catecholamines which are of neuronal or vascular origin. The specific localization of βAR404-immunoreactivity to the more distal portions of astrocytes suggests the possibility that astrocytes have restrictive distributions of βAR and that the β-adrenergic activation lead to morphological or chemical changes that are also localized to the distal portions of astrocytes. Additionally, the detection of βAR404 in astrocytes contacting non-TH-immunoreactive neurons suggests the possibility for catecholaminergic modulation of non-catecholaminergic neurons via the activation of astrocytes.