高半胱氨酸膳食对小鼠生长和免疫力的影响

探讨了高半胱氨酸膳食对小鼠生长及对外来抗原刺激产生抗体的免疫力的影响。实验取小白鼠32只,随机分为高半胱氮酸组(H)和对照组(C)各16只。H组每天给予含半胱氨酸质量分数为3％的饲料,分别在1、4、8周对其腹腔注射牛血清白蛋白,在第9周处死动物,取血测量血清抗体效价。结果显示实验组生长缓慢,血清抗体效价显著高于对照组,表明高半胱氨酸膳食可提高小鼠血清抗体效价,但高含量的半胱氨酸对小鼠生长有抑制作用。     

Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet

The role of inducible nitric oxide synthase (iNOS) in the progression of fibrosis during nonalcoholic steatohepatitis remains to be elucidated. This study examined the role of iNOS in the progression of fibrosis during steatohepatitis by comparing iNOS knockout (iNOS^−/−) and wild-type (iNOS^+/+) mice that were fed a high-fat diet. Severe fatty metamorphosis developed in the liver of iNOS^+/+ and iNOS^−/− mice. Fibrotic changes were marked in iNOS^−/− mice. Gelatin zymography showed that pro MMP-2 and pro MMP-9 protein expressions were more highly induced in iNOS^+/+ mice than in iNOS^−/− mice. Active forms of MMP-2 and MMP-9 were clearly present only in the liver tissue of iNOS^+/+ mice. In situ zymography showed strong gelatinolytic activities in the liver tissue of iNOS^+/+ mice, but only spotty activity in iNOS^−/−mice. iNOS may attenuate the progression of liver fibrosis in steatohepatitis, in part by inducing MMP-2 and MMP-9 expression and augmenting their activity.     

一种菊科植物抽提物对小鼠血液生化成分的影响

探讨一种菊科植物抽提物对小鼠血液生化成分的影响。利用半自动生化分析仪测定血液生化成分,结果表明该抽提物可降低血清白蛋白和总蛋白含量;降低乳酸脱氢酶、肌酸激酶活性和丙氧酸氧基转移酶活性;对血清中尿素、尿酸、肌酐都有明显降低作用;可减少血清二价金属离子Ca^2 、Mg^2 含量,增加Cl^-含量;对碱性磷酸酶、天冬氨酸氧基转移酶、血清无机磷影响不明显。     

Gene expression of LOX-1, VCAM-1, and ICAM-1 in pre-atherosclerotic mice

To identify markers of the earliest stage of atherosclerosis, endothelial dysfunction, we evaluated the gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in very young pre-atherosclerotic mice. Furthermore, the plasma levels of the soluble VCAM-1 and ICAM-1 were compared to the gene expression profiles. Gene expressions of LOX-1 and VCAM-1 were up-regulated in young apoE^−/− mice, and thus, it seems probable that these genes play a role in pre-atherosclerosis. Contrarily, the gene expression profile of ICAM-1 did not show any apparent differences between the groups, questioning the involvement of this molecule in the early development of atherosclerosis. Plasma levels of sVCAM-1 and sICAM-1 were similar in all mice and did not correlate with the vascular gene expression of the corresponding genes. It therefore seems likely that these circulating markers are not suited to detect early atherosclerosis.     

Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor γ (PPARγ) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARγ luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.     

The Adipose Tissue Phenotype of Hormone‐Sensitive Lipase Deficiency in Mice

Objective: To directly ascertain the physiological roles in adipocytes of hormone‐sensitive lipase (HSL; E.C. 3.1.1.3), a multifunctional hydrolase that can mediate triacylglycerol cleavage in adipocytes. Research Methods and Procedures: We performed constitutive gene targeting of the mouse HSL gene (Lipe), subsequently studied the adipose tissue phenotype clinically and histologically, and measured lipolysis in isolated adipocytes. Results: Homozygous HSL^?/? mice have no detectable HSL peptide or cholesteryl esterase activity in adipose tissue, and heterozygous mice have intermediate levels with respect to wild‐type and deficient littermates. HSL‐deficient mice have normal body weight but reduced abdominal fat mass compared with normal littermates. Histologically, both white and brown adipose tissues in HSL^?/? mice show marked heterogeneity in cell size, with markedly enlarged adipocytes juxtaposed to cells of normal morphology. In isolated HSL^?/? adipocytes, lipolysis is not significantly increased by β₃‐adrenergic stimulation, but under basal conditions in the absence of added catecholamines, the lipolytic rate of isolated HSL^?/? adipocytes is at least as high as that of cells from normal controls. Cold tolerance during a 48‐hour period at 4 °C was similar in HSL^?/? mice and controls. Overnight fasting was well‐tolerated clinically by HSL^?/? mice, but after fasting, liver triglyceride content was significantly lower in HSL^?/? mice compared with wild‐type controls. Conclusions: In isolated fat cells, the lipolytic rate after β‐adrenergic stimulation is mainly dependent on HSL. However, the observation of a normal rate of lipolysis in unstimulated HSL^?/? adipocytes suggests that HSL‐independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in mice has a modest effect under normal fed conditions and is compatible with normal maintenance of core body temperature during cold stress. However, the lipolytic response to overnight fasting is subnormal.     

Estimation of Energy Expenditure from Physical Activity Measures: Determinants of Accuracy

Objective: To describe the determinants, specifically age, body mass index, percentage of body fat, and physical activity (PA) level, associated with over‐ and underestimation of energy expenditure (EE) using PA records and the Stanford Seven‐Day Physical Activity Recall (7DR) compared with doubly labeled water (DLW). Research Methods and Procedures: We collected PA measures on 24 males eating a controlled diet designed to maintain body weight, and we determined EE from DLW and estimated EE from PA records and 7DR. Results: Absolute differences in the estimation of EE between DLW and PA assessment methods were greater for the 7DR (30.6 ± 9.9%) than PA records (7.9 ± 3.2%). In PA records, overestimation of EE was greater with older age and higher body fatness; EE was overestimated by 16.7% among men 50 years and older compared with only 5.3% among men <40 years of age. For percentage of body fat, EE was overestimated by 19.7% among men with a percentage of body fat ≥30% compared with only 5.6% among men with a percentage of body fat <25%. A trend for less overestimation of EE with higher levels of PA (measured by DLW/basal metabolic rate [BMR]) also was observed in the PA records. In the 7DR, the estimates of EE varied widely and no trends were observed by age, percentage of body fat, and PA levels. Discussion: Estimation of EE from the 7DR is considerably more variable than from PA records. Factors related to age and percentage of body fat influenced the accuracy of estimated EE in the PA record. Additional studies are needed to understand factors related to accurate reporting of PA behaviors, which are used to estimate EE in free‐living adults.     

人SR-AI转基因小鼠模型的主要形态学特性、血液学指标和血脂水平的研究

目的明确人SR-AI转基因小鼠的一些形态、脏器、血液学和血浆脂质参数,为人SR-AI转基因小鼠模型的应用提供相关依据.方法用游标卡尺和电子称量天平测量人SR-AI转基因小鼠的吻长、眶间距、体长、尾长及12个脏器系数并与C57BL/6J小鼠进行比较分析;用SysmexK-4500型全血自动多参数血液分析仪检测其血液学指标;并用酶法分别测定血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇含量.结果人SR-AI转基因小鼠外部形态指标和脏器系数与C57BL/6J小鼠比较差异没有显著意义(P>0.05);转基因小鼠的各项血液学指标无明显改变,血脂蛋白成分的改变亦未显示统计学意义(P>0.05),甘油三酯的浓度略有增高(P<0.05).结论人SR-AI转基因小鼠的外部形态指标、脏器系数及各项血液学指标均无明显改变,适合用作动脉粥样硬化模型的研究.     

Increased expression of the neuropeptide Y receptor Y1 gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone

The neurosteroid allopregnanolone, a reduced metabolite of progesterone, induces anxiolytic effects by enhancing GABA(A) receptor function. Neuropeptide Y (NPY) and GABA are thought to interact functionally in the amygdala, and this interaction may be important in the regulation of anxiety. By using Y(1)R/LacZ transgenic mice, which harbour a fusion construct comprising the promoter of the mouse gene for the Y(1) receptor for NPY linked to the lacZ gene, we previously showed that long-term treatment with benzodiazepine receptor ligands modulates Y(1) receptor gene expression in the medial amygdala. We have now investigated the effects of prolonged treatment with progesterone or allopregnanolone on Y(1)R/LacZ transgene expression, as determined by quantitative histochemical analysis of beta-galactosidase activity. Progesterone increased both the cerebrocortical concentration of allopregnanolone and beta-galactosidase expression in the medial amygdala. Finasteride, a 5alpha-reductase inhibitor, prevented both of these effects. Long-term administration of allopregnanolone also increased both the cortical concentration of this neurosteroid and transgene expression in the medial amygdala. Treatment with neither progesterone nor allopregnanolone affected beta-galactosidase activity in the medial habenula. These data suggest that allopregnanolone regulates Y(1) receptor gene expression through modulation of GABA(A) receptor function, and they provide further support for a functional interaction between GABA and neuropeptide Y in the amygdala.     

Nonlinear dynamical law governs magnetic field induced changes in lymphoid phenotype.

The results of many different types of animal and human studies dealing with the biological effects of exposure to low frequency electromagnetic fields (EMFs) have consistently been both positive and negative. We addressed the question of why this pattern had occurred so commonly in biological studies involving exposure to EMFs and hypothesized that it stemmed from the prevalent use of a linear model to characterize what are inherently nonlinear input-output relationships. The hypothesis was tested by analyzing biological data using a novel statistical procedure that could be adjusted to detect either nonlinear or linear effects. The reliability of the procedure was established using positive and negative controls and by comparison with the results obtained from sampling a known nonlinear system. In four independent experiments, male and female mice were exposed continuously to 0.1 or 0.5 mT, 60 Hz, for 175 days, and the effect on 20 immune parameters was measured using flow cytometry and functional assays. In each experiment, EMF exposure resulted in statistically significant changes in lymphoid phenotype when and only when the response of the animals to the fields was analyzed as if it were governed by nonlinear laws. Our results suggest that the pattern of inconsistency in the EMF bioeffects studies is an artifact resulting from an incorrect choice of the conceptual model for the relation between the field and the biological effect it causally determines.