Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte–M2 macrophage pathway

Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) and helper T lymphocytes (Th1 and Th2) was investigated using the spleen from rats fed zinc-deficient or standard diet. In experiment I, 5-week-old male Sprague-Dawley rats were fed a zinc-deficient diet (without zinc additives) or a standard diet (containing 0·01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc-deficient diets and were injected three times a week with either saline or interleukin-4 (IL-4) (zinc-deficient/IL-4 i.p.); a fourth group (zinc-deficient/standard) was fed a zinc-deficient diet for 6 weeks followed by a standard diet for 4 weeks. In experiment I; GATA-binding protein 3 (GATA-3) protein level, M2 macrophage, CD3⁺ CD8⁺ cells, and IL-4/IL-13-positive cells significantly decreased in the spleens of the zinc-deficient group. Additionally, IL-1β and macrophage inflammatory protein-1α (MIP-1α) mRNA levels significantly increased in the splenic macrophages of the zinc-deficient group. In experiment II; M2 macrophages, CD3⁺ CD8⁺ cells, IL-4/IL-13-positive cells, and GATA-3 protein levels significantly increased in the spleens of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Furthermore, IL-1β and MIP-1α mRNA levels decreased in the splenic macrophages of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Zinc deficiency-induced aggravated inflammation is related to Th2 lymphocytes and followed by the association with loss of GATA-3, IL-4 and anti-inflammatory M2 macrophages. Importantly, IL-4 injection or zinc supplementation can reverse the effects of zinc deficiency on immune function.     

谷氨酰胺对创伤后免疫组织细胞抗氧化能力的影响

研究经肠补充谷氨酰胺对创伤大鼠免疫组织抗氧化能力的影响。方法采用闭合性创伤大型模型,通过肠内补充或不补充Ｇｌｕ两种方式进行对比实验,观察伤后血浆,脾脏,肠系膜淋巴结和腹腔巨噬细胞内Ｇｌｕ含量,以及还原型谷胱甘肽和丙二醛水平。     

Gut immune deficits in LEW.1AR1‐iddm rats partially overcome by feeding a diabetes‐protective diet

The gut immune system and its modification by diet have been implicated in the pathogenesis of type 1 diabetes (T1D). Therefore, we investigated gut immune status in non‐diabetes‐prone LEW.1AR1 and diabetes‐prone LEW.1AR1‐iddm rats and evaluated the effect of a low antigen, hydrolysed casein (HC)‐based diet on gut immunity and T1D. Rats were weaned onto a cereal‐based or HC‐based diet and monitored for T1D. Strain and dietary effects on immune homeostasis were assessed in non‐diabetic rats (50–60 days old) and rats with recent‐onset diabetes using flow cytometry and immunohistochemistry. Immune gene expression was analysed in mesenteric lymph nodes (MLN) and jejunum using quantitative RT‐PCR and PCR arrays. T1D was prevented in LEW.1AR1‐iddm rats by feeding an HC diet. Diabetic LEW.1AR1‐iddm rats had fewer lymphoid tissue T cells compared with LEW.1AR1 rats. The percentage of CD4⁺ Foxp3⁺ regulatory T (Treg) cells was decreased in pancreatic lymph nodes (PLN) of diabetic rats. The jejunum of 50‐day LEW.1AR1‐iddm rats contained fewer CD3⁺ T cells, CD163⁺ M2 macrophages and Foxp3⁺ Treg cells. Ifng expression was increased in MLN and Foxp3 expression was decreased in the jejunum of LEW.1AR1‐iddm rats; Ifng/Il4 was decreased in jejunum of LEW.1AR1‐iddm rats fed HC. PCR arrays revealed decreased expression of M2‐associated macrophage factors in 50‐day LEW.1AR1‐iddm rats. Wheat peptides stimulated T‐cell proliferation and activation in MLN and PLN cells from diabetic LEW.1AR1‐iddm rats. LEW.1AR1‐iddm rats displayed gut immune cell deficits and decreased immunoregulatory capacity, which were partially corrected in animals fed a low antigen, protective HC diet consistent with other models of T1D.     

Stenotrophomonas maltophilia fimbrin stimulates mouse bladder innate immune response

The role of Stenotrophomonas maltophilia fimbrin (SMF) to stimulate the bladder innate immune response was evaluated in this study. SMF was isolated and purified from clinical isolates of S .maltophilia. Different amounts of SMF (1, 5 and 15 μg) was instilled transurethrally. The innate immune response was evaluated in terms of IL-1β, TNF-α, IL-8 and NO concentrations, and mRNA expressions of IL-1β, TNF-α, IL-8 and iNOS in mouse bladder tissue. Moreover, neutrophil infiltration in urine, myeloperoxidase (MPO) activity in bladder tissue and bladder epithelial cells (BECs) activity to engulf and kill bacteria in vitro was studied. The maximum pro-inflammatory cytokines (IL-1β and TNF-α) and chemokine (IL-8) concentrations and their mRNA expressions were found in bladder homogenates of mice that were instilled with 15 μg of SMF transurethrally. The high levels of these mediators was concomitant with the high level of neutrophil infiltration in bladder tissue (MPO) and in collected urine (neutrophil count). The administration of SMF transurethrally activated the BECs in terms of bacterial uptake and intracellular bacterial killing in vitro. This study showed that the SMF administration increased the level of nitric oxide (NO) in bladder tissue. The present study proved for the first time that the administration of mice with SMF transurethrally induced cellular and molecular elements of innate immune response in mouse bladder.     

Lactobacillus casei addition to a repletion diet-induced early normalisation of cytokine profils during a pneumococcal infection in malnourished mice

This work studied the influence of Lactobacillus casei on cytokine production during repletion of malnourished mice in the face of an infectious challenge. In addition, the number and function of cells involved in the immune response against a respiratory infection was evaluated. Weaned mice were malnourished after consuming a protein-free diet (PFD) for 21 days. Malnourished mice were fed a balanced conventional diet (BCD) for 7 days or BCD for 7 days with L. casei supplementation on day 6 and day 7 (BCD+Lc). The malnourished control group (MNC) received PFD while the well-nourished control (WNC) mice consumed BCD. Mice were challenged intranasally with Streptococcus pneumoniae at the end of each dietary treatment. Malnutrition impaired the levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-4, IL-6 and IL-10. In addition, neutrophil number and activity, lymphocyte maturation and bone marrow CD4+, CD8+ and CD19+ cells number, were also impaired in the MNC group. Repletion with BCD induced a slight improvement in some of the parameters studied. However, when L. casei was added to the BCD, a normalisation of TNF-α, IL-1β and IL-6 values after infection and an increase in the levels of IL-10 and IL-4 compared to the WNC group was observed. Moreover, BCD+Lc induced a significant improvement in blood and bone marrow cells. Consequently, the use of L. casei as a supplement in a repletion diet was associated with a pattern of inflammatory and anti-inflammatory cytokines that led to an increased number and functionality of the cells that participate in the immune response against a pneumococcal infection.     

Reduced ratio of protective versus proinflammatory cytokine responses to commensal bacteria in HLA-B27 transgenic rats

Germ-free HLA-B27 transgenic (TG) rats do not develop colitis, but colonization with specific pathogen-free (SPF) bacteria induces colitis accompanied by immune activation. To study host-dependent immune responses to commensal caecal bacteria we investigated cytokine profiles in mesenteric lymph node (MLN) cells from HLA-B27 TG versus nontransgenic (non-TG) littermates after in vitro stimulation with caecal bacterial lysates (CBL). Supernatants from CBL-stimulated unseparated T- or B- cell-depleted MLN cells from HLA-B27 TG and non-TG littermates were analysed for IFN-gamma, IL-12, TNF, IL-10 and TGF-beta production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN-gamma, IL-12 and TNF than did non-TG MLN cells. In contrast, CBL-stimulated non-TG MLN cells produced more IL-10 and TGF-beta. T cell depletion abolished IFN-gamma and decreased IL-12 production, but did not affect IL-10 and TGF-beta production. Conversely, neither IL-10 nor TGF-beta was produced in cultures of B cell-depleted MLN. In addition, CD4(+) T cells enriched from MLN of HLA-B27 TG but not from non-TG rats produced IFN-gamma when cocultured with CBL-pulsed antigen presenting cells from non-TG rats. Interestingly, IL-10 and TGF-beta, but not IFN-gamma, IL-12 and TNF were produced by MLN cells from germ-free TG rats. These results indicate that the colitis that develops in SPF HLA-B27 TG rats is accompanied by activation of IFN-gamma-producing CD4(+) T cells that respond to commensal bacteria. However, B cell cytokine production in response to components of commensal intestinal microorganisms occurs in the absence of intestinal inflammation.     

Effect of the Achillea wilhelmsii extract intake upon blood lipid profile,haematologic and immunologic parameters in the rat

Achillea species are widely used in folk medicine as antispasmodic, choloretic, antiphlogistic, antifungal and antibacterial agents, but little is known about their effects on the immune system and blood lipid profile. In this study, effects of the Achillea wilhelmsii methanolic extracts (ME) upon the lipid, haematological parameters and immune system were examined. ME was given at dose 75 mg/kg/day for 30 days to Sprague–Dawley rats fed with high-fat diet. Haematology, flow cytometry, clinical, biochemical and histopathological examinations were performed in the sacrificed animals. Significant decreases in triglyceride and very low density lipoprotein cholesterol, and increases in CD4 expression in lymphocytes and monocytes were observed. Assessment of alanin aminotransferase, aspartat aminotransferase activities, histopathological examinations and proinflammatory cytokine levels (IL-1β, IL-6, IL-10, TNF-α) showed neither liver damage nor inflammation induction. Beside the improvements in lipid profile by ME treatment without any liver damage and inflammation, the increase of CD4 expression both on lymphocyte and monocyte populations need further investigation.     

基于AMPK/mTOR信号通路介导的自噬途径研究黄芪多糖对急性放射性肠炎大鼠肠黏膜的保护作用

目的:探究基于AMP活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路介导的自噬途径研究黄芪多糖(APS)对急性放射性肠炎大鼠肠黏膜的保护作用.方法:对SD大鼠进行12 Gy单次照射,制备急性放射性肠炎模型,随机分为模型组、APS(2 g/kg)组、AMPK抑制剂compound C(CC,0.2 m...     

Modulatory Effect of Whey Proteins in Some Cytokines Involved in Wound Healing in Male Diabetic Albino Rats

The anti-inflammatory cytokines (interleukin (IL)-4 and IL-10) and the pro-inflammatory cytokines (IL-1β, IL-6, and tumor necroses factor-alpha (TNF-α)) have important functions in wound healing. Thus, the aim of this study was to determine whether dietary supplementation with whey protein could enhance normal inflammatory responses during wound healing in diabetic rats. In this study, male albino rats were divided into a wounded control group, a wounded diabetic group, and a wounded diabetic group supplemented with whey protein orally at a dose of 100 mg/kg body weight. Tested rats showed increasing wound closure in rats treated with whey protein. In addition, after 4 days of wound, modulation in IL-4, IL-10, IL-1β, IL-6, and TNF-α levels were detected. Statistical analysis of data showed significant difference between the whey-protein-treated group and either control or diabetic groups (P?相似文献   

Dendritic cell chemotaxis and transendothelial migration are induced by distinct chemokines and are regulated on maturation

The capacity of dendritic cells (DC) to initiate immune responses is dependent on their specialized migratory and tissue homing properties. Chemotaxis and transendothelial migration (TEM) of DC were studied in vitro. Immature DC were generated by culture of human monocytes in granulocyte-macrophage colony-stimulating factor and IL-4. These cells exhibited potent chemotaxis and TEM responses to the CC chemokines macrophage inflammatory protein (MIP)-1α, MIP-1β, RANTES, and monocyte chemotactic protein-3, and weak responses to the CC chemokine MIP-3β and the CXC chemokine stromal cell-derived factor (SDF)-1α. Maturation of DC induced by culture in lipopolysaccharide, TNF-α or IL-1β reduced or abolished responses to the former CC chemokines but markedly enhanced responses to MIP-3β and SDF-1α. This correlated with changes in chemokine receptor expression: CCR5 expression was reduced while CXCR4 expression was enhanced. These findings suggest two stages for regulation of DC migration in which one set of chemokines may regulate recruitment into or within tissues, and another egress from the tissues.     

Effect of polysaccharides of the Euphoria longan (Lour.) Steud on inflammatory response induced by focal cerebral ischemia/reperfusion injury in rats

Stroke induces cerebral lesions through the combined action of multiple mechanisms, the inflammatory response on the damage of cerebral tissues after ischemia has become a focus. The Euphoria longan (Lour.) Steud is a fruit and traditional Chinese medicine, with the function of anti-inflammatory and immune regulation. In the present experiments, we investigate the mechanisms underlying the inhibitory effects of polysaccharides of the E. longan (Lour.) Steud on inflammatory responses induced by middle cerebral artery occlusion (MCAO) in rats. Compared with model group, polysaccharides of the E. longan (Lour.) Steud could obviously reduce the neurological function score, the brain water content, the infract volume, the myeloperoxidase (MPO) activity, the tumor necrosis factor-α(TNF-α) and interleukin-1β (IL-1β) level. Polysaccharides of the E. longan (Lour.) Steud have a protective effect on cerebral ischemia/reperfusion injury, which may be related to decreasing inflammatory response mediated by MPO, TNF-α and IL-1β in the brain.     

Bone marrow mononuclear cells enhance anti-inflammatory effects of pravastatin against isoproterenol-induced myocardial infarction in rats

The current study investigated the combinatorial effect of pravastatin (PRAV) and bone marrow mononuclear cells (BM-MNC) on acute myocardial infarction (AMI) induced experimentally in rats. After induction of MI, rats were given oral PRAV (20?mg/kg/day) for 28 days or a bolus intravenous injection (via lateral vein) of a total of 14?×?10⁶ autologous BM-MNC or a combination of both. Serum brain natriuretic peptide (BNP) and histologic changes in cardiac tissues were assessed. Cardiac contents of lipid peroxides, superoxide dismutase (SOD) and inflammatory biomarkers including tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) were also measured. Combined PRAV and BM-MNC treatment significantly suppressed serum BNP. Cardiac cell apoptosis and inflammatory cell infiltration in heart tissue decreased significantly in both the PRAV and the PRAV?+?BM-MNC groups. Cardiac lipid peroxides along with TNFα and IL-1β levels were significantly reduced in both the PRAV and PRAV?+?BM-MNC hosts with an increase in SOD levels. However, the combined treatment increased cardiac NO levels and did not modify cardiac VEGF levels. The current results indicated that administration of BM-MNC improved the therapeutic efficacy of PRAV treatment by improving the morphology of infarcted hearts as well as decreasing inflammation in a host, but did not do so by inducing therapeutic angiogenesis.     

苦参碱对溃疡性结肠炎大鼠肠黏膜细胞因子和自由基的影响

目的探究苦参碱对溃疡性结肠炎大鼠肠黏膜细胞因子和自由基的影响及其机制。方法采用2,4,6-三硝基苯磺酸（TNBS）制造大鼠溃疡性结肠炎模型,运用苦参碱对大鼠溃疡性结肠炎进行治疗,以柳氮磺胺吡啶作为阳性对照。治疗结束后,剖取结肠,检测黏膜细胞中IL-1α、TNF-α、IL-6和IL-8等细胞因子的水平;检测结肠黏膜细胞中超氧化物歧化酶（SOD）、丙二醛（MDA）水平。另取部分结肠做组织显微镜检查,并对组织损伤评分进行数理统计。结果与模型组相比,苦参碱和柳氮磺胺吡啶均能极显著降低IL-1β、TNF-α、IL-6和IL-8水平（均P〈0．01）;与模型组相比,苦参碱和柳氮磺胺吡啶均能极显著升高结肠黏膜细胞SOD水平（P〈0．01）,极显著降低MDA水平（P〈0．01）;苦参碱和柳氮磺胺吡啶均能促进溃疡面愈合,减少病灶部位炎性细胞浸润,水肿及纤维化。结论苦参碱能明显抵抗溃疡性结肠炎炎性反应,增强机体免疫,通过调节肠黏膜细胞因子失衡和抑制黏膜细胞氧自由基的产生和抗氧化功能干预溃疡性结肠炎发病过程。     

Effect of combined supplementation with vitamin E and alpha‐lipoic acid on myocardial performance during in vivo ischaemia‐reperfusion

Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia‐reperfusion (I‐R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha‐lipoic acid (α‐LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I‐R. The purpose of these experiments was to investigate the effects of VE and α‐LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I‐R insult. Female Sprague–Dawley rats (4‐months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and α‐LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN‐93M standards, which contains 75 IU VE kg^–1 diet. The ANTIOXID diet contained 10 000 IU VE kg^–1 diet and 1.65 g α‐LA kg^–1 diet. After the 14‐week feeding period, significant differences (P < 0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I‐R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P > 0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I‐R protocol. Following I‐R, two markers of lipid peroxidation were lower (P < 0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and α‐LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in vivo I‐R in young adult rats.     

Expression of cytokine mRNAs in murine hearts with acute myocarditis caused by coxsackievirus B3

In murine acute viral myocarditis, natural killer (NK) cells infiltrate the heart first, followed by activated T-cells, which play an important role in the pathogenesis of the myocardial damage. Because of their multipotential effects, cytokines are thought to play a role in the induction and development of these immune processes. To clarify in more detail the precise mechanism of the cytokine networks involved, the expression of various cytokine mRNAs has been investigated in myocardial cells infected with Coxsackievirus B3 (CVB3) in vivo and in vitro by a semiquantitative polymerase chain reaction (PCR) method. Interleukin (IL)-1α, IL-1β, IL-6, tumour necrosis factor (TNF)-α, and TNF-β were expressed almost throughout the early phase of virus infection with some variations. IL-2, IL-3, IL-4, IL-10, interferon (IFN)-γ, granulocyte/macrophage colony stimulating factor (GM-CSF), and IL-2 receptor (IL-2R) were mainly expressed by the infiltrating cells. TNF-α, TNF-β, and IL-1β were also expressed partly by the infiltrating cells. T-helper (Th)1-related cytokines (IL-2, IFN-γ, and TNF-β) were more strongly expressed than Th2-related cytokines (IL-4 and IL-10) in vivo, indicating that the Th cells which infiltrated the heart and mediated the immune responses in the early phase of acute myocarditis were mainly of Th1-type. © 1997 by John Wiley & Sons, Ltd.     

HSYA对骨关节炎大鼠膝关节软骨损伤的修复作用研究

目的探讨羟基红花黄色素A(HSYA)对骨关节炎(OA)大鼠膝关节及MMP-3、TGF-β1、Notch1的影响。方法将25只大鼠随机分为正常组(假手术)、OA组(模型大鼠)、低HSYA组(模型大鼠尾部注射2.5 mg/kg HSYA)、中HSYA组(模型大鼠尾部注射5.0 mg/kg HSYA)、高HSYA组(模型大鼠尾部注射10.0 mg/kg HSYA)。采用ELISA检测血清指标IL-1β、TNF-α,Pelletier评分评估膝关节软骨损伤情况,HE染色观察组织病理形态并以Mankin评分进行评估,免疫组化检测MMP-3阳性表达,Western blot检测TGF-β1、Notch1蛋白水平。结果OA组血清中IL-1β、TNF-α水平高于其余各组(P<0.05),高HSYA组IL-1β、TNF-α水平低于低HSYA组和中HSYA组(P<0.05)。各组大鼠Pelletier评分组间比较差异有统计学意义(P<0.05)。OA组软骨和滑膜组织Mankin评分高于其余各组(P<0.05),高HSYA组Mankin评分低于低HSYA组、中HSYA组(P<0.05)。各组大鼠关节组织MMP-3阳性细胞率组间比较差异有统计学意义(P<0.05)。各组大鼠关节组织TGF-β1、Notch1蛋白水平组间比较差异有统计学意义(P<0.05)。结论HSYA能够降低OA大鼠血清炎性因子IL-1β、TNF-α水平,缓解滑膜组织损伤,且存在浓度依赖性,其机制与抑制MMP-3和Notch1表达、提高TGF-β1水平相关。     

Parasites alter the pathological phenotype of lupus nephritis

Abstract

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis.     

Human and mouse perforin are processed in part through cleavage by the lysosomal cysteine proteinase cathepsin L

Summary Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4⁺ T cells play a critical role in protective immunity, and that CD4⁺ T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4⁺ T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4⁺ T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post‐T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4⁺ T cells marked by down‐regulation of CD62L. These cells can be isolated from intestine‐draining mesenteric lymph nodes (MLN) from day 14 post‐infection, but are rare or absent in MLN before this and in spleen at all times post‐infection. Among CD4⁺ CD62L^low MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4⁺ CD62L^low T‐cell migration to the large intestinal mucosa is dependent on the family of Gα_i‐coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4⁺ CD62L^low cell migration to the large intestinal mucosa during T. muris infection.     

高脂饮食对大鼠海马、大脑皮质和脊髓GDNF表达的影响

目的:探讨高脂饮食对大鼠海马、大脑皮质和脊髓胶质细胞源性神经营养因子(GDNF)的影响。方法:20只雄性SD大鼠随机分成两组:普通饮食组(ND)和高脂饮食组(HFD),每组10只,分别给予两组大鼠普通饮食和高脂饮食14周,测量各组大鼠体重、脂肪重、Lee’s指数和脂体比。应用real time RT-PCR检测各组大鼠海马、大脑皮质和脊髓GDNF mRNA的表达;应用Western Blot检测各组大鼠海马、大脑皮质和脊髓GDNF蛋白的表达;应用酶联免疫吸附实验(ELISA)检测各组大鼠海马、大脑皮质和脊髓肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-6的水平。结果:高脂饮食导致大鼠体重、脂肪重、Lee’s指数和脂体比均明显升高(P <0.05); HFD组大鼠海马、大脑皮质和脊髓GDNF mRNA表达水平较ND组均显著下降(P <0.01),HFD组大鼠海马、大脑皮质和脊髓GDNF蛋白表达水平较ND组均明显下降(P <0.05); HFD组大鼠海马、大脑皮质和脊髓中TNF-α、IL-1β和IL-6水平与ND组相比均明显升高(P <0.0...