多烯磷脂酰胆碱联合异甘草酸镁治疗药物性肝损害疗效观察

目的观察多烯磷脂酰胆碱联合异甘草酸镁治疗药物性肝损害的临床疗效。方法观察组以多烯磷脂酰胆碱联合异甘草酸镁治疗药物性肝损害128例,对照组以甘草酸二胺治疗药物性肝损害92例,治疗结束后观察其症状、体征以及肝功能的变化。结果 2周后两组患者丙氨酸氨基转移酶、天门冬酸氨基转移酶及总胆红素较治疗前均明显下降,组内差异有统计学意义（P〈0.05）,两组之间差异无统计学意义（P〉0.05）,观察组显效率（75.78%）高于对照组显效率（64.13%）,差异有统计学意义（P〈0.05）。结论多烯磷脂酰胆碱联合异甘草酸镁可明显改善药物性肝损害的临床症状和肝功能指标,且显效率高,不良反应少。     

Inhibition of phospholipase A₂ in rat brain modifies different membrane fluidity parameters in opposite ways

Fluidity is an important neuronal membrane property and it is influenced by the concentration of polyunsaturated fatty acids (PUFAs) in membrane phospholipids. Phospholipase A₂ (PLA₂) is a key enzyme in membrane phospholipid metabolism, generating free PUFAs. In Alzheimer disease (AD), reduced PLA₂ activity, specifically of calcium-dependent cytosolic PLA₂ (cPLA₂) and calcium-independent intracellular PLA₂ (iPLA₂), and phospholipid metabolism was reported in the frontal cortex and hippocampus. This study investigated the effects of in vivo infusion of the dual cPLA₂ and iPLA₂ inhibitor MAFP into rat brain on PLA₂ activity and membrane fluidity parameters in the postmortem frontal cortex and dorsal hippocampus. PLA₂ activity was measured by radioenzymatic assay and membrane fluidity was determined by fluorescence anisotropy technique using three different probes: DPH, TMA-DPH, and pyrene. MAFP significantly inhibited PLA₂ activity, reduced the flexibility of fatty acyl chains (indicated by increased DPH anisotropy), increased the fluidity in the lipid-water interface (indicated by decreased TMA-DPH anisotropy), and increased the lipid lateral diffusion in the hydrocarbon core (represented by pyrene excimer formation) of membranes in both brain areas. The findings suggest that reduced cPLA₂ and iPLA₂ activities in AD brain might contribute to the cognitive impairment, in part, through alterations in membrane fluidity parameters.     

多烯磷脂酰胆碱对非酒精性脂肪肝大鼠脂肪组织相关基因表达的影响

目的 在脂肪组织基因表达水平上分析多烯磷脂酰胆碱对非酒精性脂肪肝(NAFLD)大鼠模型的干预效果及其作用机制.方法 以高脂饲料饲养Wistar大鼠诱发NAFLD并进行多烯磷脂酰胆碱干预,通过RT-qPCR方法 检测实验大鼠脂肪组织瘦素、肿瘤坏死因子α、脂联素、抵抗素和解偶联蛋白2的mRNA相对水平,并以t-检验进行数据统计分析.结果 干预组瘦素mRNA相对水平高于对照组(P>0.05),干预组肿瘤坏死因子αmRNA相对水平显著高于对照组(P<0.05),所有干预组样品的脂联素、抵抗素和解偶联蛋白2的mRNA均未被检测到.结论 多烯磷脂酰胆碱有助于增加瘦素基因的表达并适用于肥胖原因所致的NAFLD病例.     

In vitro cytotoxicity of polychlorinated biphenyls (aroclors 1016, 1242, 1254 and 1260) and their effect on phospholipid and neutral lipid composition of Chinese hamster ovary (CHO-K1) cells

Cytotoxicity of 4 Aroclors (1016, 1242, 1254 and 1260) was compared in Chinese hamster ovary (CHO-K1) cells in Ham's F-12 medium. When parameters of toxicity were cell numbers or tissue protein, 50% lethality occurred at Aroclor concentrations between 30 and 45 ppm. An in vitro clonal assay with CHO-K1 cells was a sensitive indicator of cytotoxicity of the polychlorinated biphenyls (PCBs). From EC₅₀ values (concentration that allowed 50% survival of formed colonies), cytotoxicity was lower with Aroclor 1016 (32 ppm) and higher with Aroclors 1254 (27 ppm) and 1260 (28 ppm). In cells exposed 24 h to a marginally cytotoxic dose (20 ppm) of each Aroclor, phospholipid (PL) thin-layer chromatography (TLC) showed an increase in phosphatidylcholine (PC) and a decrease in phosphatidylethanolamine (PE) and diphosphatidylglycerol (DPG). Neutral lipid (NL) TLC of cells given Aroclors 1242, 1254 or 1260 showed a 3–4-fold increase in triglyceride (TG) and a similar reduction in cholesteryl esters (CE); in contrast to Aroclor 1016 which produced no change in TG and a smaller (2-fold) reduction in CE. Cholesterol and free fatty acid fractions were unaffected by any of the Aroclors. The TG:PL ratio remained unchanged in cells given Aroclor 1016, but increased 3–4-fold with Aroclors 1242, 1254, or 1260. Compared to total values in the untreated controls, CHO-K1 cells contained less neutral lipid and more phospholipid only with Aroclor 1016.These results support the concept that differences in the behavior of Aroclor 1016 are related to its PCB composition. Changes in membrane PL and NL components, observed at marginally cytotoxic levels of each Aroclor, provided further evidence that the PCBs may affect membrane integrity and associated metabolic functions.     

Systematically applied chemicals that damage lung tissue

A large, and increasing number of drugs and chemicals have been found which are toxic to lung following systemic administration. These agents damage lung tissue specifically, or in addition to damage to other tissues. Mechanisms explaining the pulmonary damage produced by some lung toxins have been uncovered. These include concentration of the agent within lung, the absence of adequate pulmonary detoxication systems, and bioactivation to a toxic species within specific lung cells or at distant sites followed by transport to the lung. The basic biochemical lesions underlying lung damage, responses of individual lung cells and pulmonary repair processes to the toxic agent, and species and age differences in susceptibility to lung damage have not, however, been well defined for most lung toxins. This review describes the information available on pulmonary biochemical and pathological changes associated with some of these lung-toxic agents. In addition, mechanisms proposed to explain the lung damage are discussed. The agents covered include: paraquat, the thioureas, butylated hydroxytoluene, the trialkylphosphorothioates, various lung-toxic furans and antineoplastic agents, the pyrrolizidine alkaloids, metals and organometallic compounds, amphiphilic agents, hydrocarbons, oleic acid, 3-methylindole, and diabetogenic agents. Detailed reviews on the overall toxicity of many of these agents have been published elsewhere. This review concentrates on their pulmonary toxicity. Information is presented as an overview to illustrate both the extensive literature that is available and the important questions that remain to be answered about systemic chemicals that damage lung tissue.     

Protective effect of polyunsaturated phosphatidylcholine pretreatment on stress ulcer formation in rats

Purpose

The aim of this study was to investigate whether polyunsaturated phosphatidylcholine. (PPC) pretreatment has any protective effect on gastric mucosal damage induced by cold-restraint stress (CRS) in rats.

Methods

Forty swiss albino rats were divided into 3 groups. Group 1 (n = 10) was control, group 2 (n = 15) was stress ulcer, and group 3 (n = 15) was PPC-treated rats with stress ulcer. Stress ulcer was induced by the cold-restraint method for 4 hours at 4°C after a starvation period of 72 hours. In the group 3 rats, PPC treatment was started 10 days before stress at a dose of 100 mg/d by oral route. Rats were terminated, stomachs were excised. Macroscopic ulcer index (UI), gastric tissue malondialdehyde (MDA) and superoxide dismutase (SOD) activities, plasma total nitrite, and erythrocyte catalase (CAT) concentrations were assayed.

Results

Histopathologic examination showed a stress ulcer index of 0.12 ± 0.19 mm in the treatment group and 23.6 ± 8.97 mm in the stress ulcer group (P < .001). Tissue MDA and SOD concentrations were higher in the stress ulcer group than in the treatment group, the differences were statistically significant (P < .001). Plasma NO₃⁻+ NO₂⁻ levels were higher (P< .005) and CAT levels were lower (P < .001) in the nontreatment group. There were no significant differences with respect to Ul, MDA, and SOD levels among the control and treatment groups (P > .05).

Conclusions

These results suggest that pretreating rats with PPC inhibits cold-restraint stress-induced gastric mucosal injury and might be useful in preventing stress-induced stomach ulcers.     

The role of CD36 in peripheral nerve remyelination after crush injury

We previously demonstrated that the deficiency of class A macrophage scavenger receptor type I/II was involved in the delayed phagocytosis of degraded myelin by macrophages in class A macrophage scavenger receptor type I/II knockout mice after crush injury of the sciatic nerve [Naba et al. (2000) Exp. Neurol., 166, 83-89]. In order to elucidate the role of CD36, one of the scavenger receptors, here we inflicted crush injury to the sciatic nerves of CD36 knockout mice and investigated the remyelination after crush injury in comparison with that of class A macrophage scavenger receptor type I/II knockout mice. Although we previously reported a lot of onion-bulbs in class A macrophage scavenger receptor type I/II knockout mice at 3 weeks, the number of onion-bulbs was limited both in CD36 knockout mice and wild-type mice. In the morphometry, the remyelination was seriously delayed, and the infiltrating macrophages into the nerve fascicles were quite frequent in CD36 knockout mice compared with wild-type mice at 3 and 6 weeks postinjury. The immunohistochemistry with the monoclonal antibody reacted with oxidized phosphatidylcholine and oil red O staining were positive in wild-type mice, but were negative in CD36 knockout mice, suggesting that the oxidation of phosphatidylcholine and the generation of neutral lipids in macrophages were disturbed in CD36 knockout mice. We hypothesize that the delayed phagocytosis by macrophages and the defect in reuse of lipids from degraded myelin are related to seriously delayed remyelination and a small number of onion-bulbs in CD36 knockout mice.     

The Cholinergic Neuronal Phenotype in Alzheimer's Disease

The synthesis, storage and release of acetylcholine (ACh) requires the expression of several specialized proteins, including choline acetyltransferase (ChAT) and the vesicular ACh transporter (VAChT). The VAChT gene is located within the first intron of the ChAT gene. This unique genomic organization permits coordinated activation of expression of the two genes by extracellular factors. Much less is known about factors that reduce the expression of the cholinergic phenotype. A cholinergic deficit is one of the primary features of Alzheimer’s disease (AD), and AD brains are characterized by amyloid deposits composed primarily of Aβ peptides. Although Aβ peptides are neurotoxic, part of the cholinergic deficit in AD could be attributed to the suppression of cholinergic markers in the absence of cell death. Indeed, we and others demonstrated that synthetic Aβ peptides, at submicromolar concentrations that cause no cytotoxicity, reduce the expression of cholinergic markers in neuronal cells. Another feature of AD is abnormal phospholipid turnover, which might be related to the progressive accumulation of apolipoprotein E (apoE) within amyloid plaques, leading perhaps to the reduction of apoE content in the CSF of AD patients. ApoE is a component of very low density lipoproteins (VLDL). As a first step in investigating a potential neuroprotective function of apoE, we determined the effects of VLDL on ACh content in neuronal cells. We found that VLDL increases ACh levels, and that it can partially offset the anticholinergic actions of Aβ peptides.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.