C57BL/6 and DBA/1 Mice Differ in Their Response to Supplementation with 1,25D and Paricalcitol

Active vitamin D (1,25D) is a fat-soluble vitamin that is mainly produced in the skin by the conversion of 7-dehydrocholesterol under ultraviolet light stimulation.Its role in calcium homeostasis,bone growth, and prevention of rickets and osteomalacia has been known for over two hundred years.Its

Ⅱ型糖尿病模型C57BL／KsJ-db／db小鼠的生物学特性研究

目的对C57BL／KsJ—db／db小鼠进行生物学特性研究，满足国内糖尿病研究者的需要。方法随机选取实验鼠进行繁殖性状数据及生长数据测试；并测定其空腹、随机血糖，以及进行糖耐量试验。结果C57BL／KsJ—db／db小鼠从3周龄开始体重迅速增加，显示过度肥胖和糖尿病症兆，并且随年龄增加血糖逐步升高。结论对C57BL／KsJ—db／db小鼠所做的相关生物学特性检测，可供糖尿病研究参考。

EFFECTS OF MODERATE NOISE EXPOSURE ON HEARING FUNCTION IN C57BL/6J MICE

Objective To study characteristics of hearing loss after exposure to moderate noise exposure in C57BL/6J mice. Methods Male C57BL/6J mice with normal hearing at age of 5-6 weeks were chosen for this study. The mice were randomly sclccted to be studied immediately after exposure （Group P0）, or 1 day （Group P1）, 3 days （Group P3）, 7 day （Group P7） or 14 days （P14） after exposure. Their before exposure condition served as the normal control. All mice were exposed to a broad-band white noise at 100 dB SPL for 2 hours, ABR thresholds were used to estimate hearing status at each time point. Results ABR threshold elevation was seen at every tested frequency at P0 （P〈0.01）. Elevation at high-frequencies （16 kHz and 32 kHz） was greater than at lower frequencies （4 kHz and 8 kHz, P〈0.05）. From P1 to P14, ABR thresholds continuously improved, and there was no significant difference between P14 and before exposure （P〉0.05）. Conclusion There is a frequency specific re- sponse to 100 dB SPL broad-band white noise in C57BL/6J mice, with the high-frequency being more susceptible. Hearing loss induced by moderate noise exposure appears reversible in C57BL/6J mice.

A murine model of dengue virus infection in suckling C57BL/6 and BALB/c mice

Dengue is a significant public health concern across tropical and subtropical regions worldwide,principally causing disease in children.Very young children are at increased risk of severe manifestations of dengue infection.The mechanism of dengue disease in this population is not fully understood.In this study,we present a murine model of dengue virus primary infection in suckling C57BL/6 and BALB/c mice in order to investigate disease pathogenesis.Three-day-old C57BL/6 mice intraperitoneally infected with DENV-2 NGC were more susceptible to infection than BALB/c mice,showing increased liver enzymes,extended viremia,dissemination to organs and histological alterations in liver and small intestine.Furthermore,the immune response in DENV-infected C57BL/6 mice exhibited a marked Th1 bias compared to BALB/c mice.These findings highlight the possibility of establishing an immunocompetent mouse model of DENV-2 infection in suckling mice that reproduces certain signs of disease observed in humans and that could be used to further study agerelated mechanisms of dengue pathogenesis.

Anti-leukemic and anti-angiogenic effects of D-Limonene on K562-implanted C57BL/6 mice and the chick chorioallantoic membrane model

Background: D-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of D-Limonene on a K562-induced model of chronic myeloid leukemia(CML) in C57 BL/6 mice.Method: The tail vein injection model of K562 cells in immunocompromised C57 BL/6 mice was developed and evaluated for characteristics of the disease. The mice were treated with D-Limonene and evaluated for haematological parameters. We also evaluated the effect of D-Limonene on angiogenesis using the chick chorioallantoic membrane(CAM) assay.Results: In a complete blood count, a significant dose-dependent reduction in white blood cell, neutrophil and lymphocyte counts, but an elevation in red blood cell count and haemoglobin content was observed with D-Limonene treatment compared to the disease control or untreated group. In the CAM assay, D-Limonene produced a significant dose-dependent reduction in number of blood vessels in treatment groups compared to the vehicle-treated group.Conclusion: These studies suggest promising anti-leukemic and anti-angiogenic effects of D-Limonene in the treatment of CML.

Differences in action potential propagation speed and axon initial segment plasticity between neurons from Sprague-Dawley rats and C57BL/6 mice

Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kinetics.Most learning and memory studies at the single-neuron level have relied on the use of animal models,most notably rodents.Here,we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley(SD)rats and C57BL/6(C57)mice with genetically encoded voltage indicator(GEVI)-based voltage imaging.Our data showed that APs traveled bidirectionally in neurons from both species;forward-propagating APs(fpAPs)had a different speed than backpropagating APs(bpAPs).Additionally,we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites.Compared with rat neurons,mouse neurons exhibited higher bpAP speed and lower fpAP speed,more distally located ankyrin G(AnkG)in AISs,and longer Nav1.2 lengths in AISs.Moreover,during AIS plasticity,AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons;in mouse neurons,however,they showed a longer AnkG-labeled length and more distal Nav1.2 location.Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds,different AnkG and Nav1.2 patterns in the AIS,and different AIS plasticity properties,indicating that comparisons between these species must be carefully considered.

Ultraviolet-attenuated cercariae ofSchistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice

Objective： To better understand the reason that Schistosoma japonicurn （S. japonicum） ultraviolet （UV）- radiated cercariae could not induce high level of protection in C57BL/6 mice. Methods： Microarray technology was performed to investigate the gene transcription profile in skin draining lymph nodes （sdLNs） at 1 w after exposure to attenuated cercariae （AC） or normal cercariae （NC） of S. japonicum in C57BL/6 mice. The expressions of some representative genes were further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from AC-vaccinated and NC- infected mice were analyzed by real-time PCR at w 3 and 6 post-exposure. Results： The gene expressions of Th1 cytokines, including interferon-y （IFN-γ）, interleukin （IL）-12 and tumor necrosis factor-α （TNF-α） in the sdLNs were significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4 and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In addition, cytotoxicity-related molecules including granzyme A, granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early stage of vaccination, and peaked at the 3rd w after vaccination with UV-AC. Conclusion： UV-AC of S. japonicum could not ef- fectively induce a Thl response in C57BL/6 mice, which may be an explanation for the low protection against parasite challenge, and the role played by up-regulated expression of cytotoxicity-related genes in mice needs to be further investigated.

Different sources of MSCs on pulmonary fibrosis in C57BL/6 mice

Since stem cell therapy is the most effective treatment in the field of tissue reparation and reconstitution,the present study aimed to explore the different sources of mesenchymal stem cells(MSCs)on the different effects of pulmonary fibrosis-related cytokines in C57BL/6 mice.For reaching this goal,we isolated MSCs from umbilical cord blood and placenta and used for stem cell therapy in a mouse model of pulmonary fibrosis model.The pulmonary fibrosis model was done by injecting bleomycin into the trachea of C57BL/6 mice.Then we assessed the degree of pulmonary fibrosis in each mouse lung tissue at weeks 1,2,3,and 4.In addition,flow cytometry was used to evaluate the frequency of CD73,CD90,CD106,CD34,CD45,CD14 cells at the mononuclear cell level;and western blotting assays revealed the expression of IκB-α.Our results showed that stem cell therapy by placenta-derived MSC had a lower level of CD34,CD45,CD14 cells at the mononuclear cell level,and that improved pulmonary fibrosis at both molecular and pathological levels.In addition,western blotting assays revealed that the expression of IκB-αwas down-regulated in MSC-treated animals.In addition,placenta-derived MSC was the most effective in improving pulmonary fibrosis in comparison to other sources.This study suggests that MSC might be a novel therapeutic approach in pulmonary fibrosis due to an enhanced anti-inflammatory effect.Also,MSC modification by gene editing could enhance their therapeutic effect in mouse pulmonary fibrosis.

Dietary Effect of Squalene on Lipid Metabolism of Obese/Diabetes KK-<i>A^y</i>Mice and Wild-Type C57BL/6J Mice

The purpose of this study was to evaluate the influence of squalene (SQ) on plasma and hepatic lipid levels of obese/diabetic KK-Ay mice and wild-type C57BL/6J mice. SQ supplementation significantly increased the HDL cholesterol of KK-Ay mice, which was paralleled with no significant difference in the total and non-HDL cholesterol levels. The increase in HDL cholesterol was also found in the plasma of normal C57BL/6J mice, but the difference was not significant. SQ administration significantly increased neutral lipids (NL) in the liver of KK-Ay mice, while no significant difference was observed in the polar lipids and the total cholesterol levels. The increase in NL was primarily due to the increase in TAG. However, the cholesterol level significantly increased due to SQ intake in the liver of C57BL/6J mice, while no significant difference was found in other lipid levels. The present study suggests that SQ may effectively increase HDL cholesterol level, an important anti-atherosclerotic factor, especially in subjects with metabolic disorders.

Characterization of Endophytes Isolated from <i>Eclipta prostrate</i>and Roles in Regulating the Gut Microbiota of C57BL/6J Mice

Eclipta prostrata has been extensively studied for its promoting effect on human health. Previous study proved that E. prostrata possessed anti-osteoporosis function in SAMP6 mice via gut microbiota (GM). Endophytes are widespread in plants, especially in Chinese herbal medicines. However, little is known regarding the endophytes of E. prostrata. In this study, we focus on screening and identifying the endophytes from plant E. prostrata and exploring their roles in modulating GM. According to biochemical, physiological tests and 16S rDNA sequence analysis, ten endophytes were characterized in different locations of plant E. prostrata belonging to Lactococcus, Bacillus, Enterococcus, Exiguobacterium and Pantoea. The antimicrobial activity of endophytes EP01-10 was investigated via the oxford cup method. Furthermore, the acid and bile salt resistant ability of EP01-10 was detected to explore their survival ability in gastrointestinal tract. Results indicated that strains of Lactococcus, Bacillus and Exiguobacterium (EP01, 03 and 05) showed strong antimicrobial activity against Escherichia coli and Staphylococcus aureus and strains of Lactococcus, Bacillus and Enterococcus (EP01, 02, 04, 08 and 10) have the ability to survive in the gastrointestinal tract. 16S rRNA sequencing of GM in C57BL/6J mice was performed for diversity and structure analysis responded to the administration of E. prostrata extract. E. prostrata extract acted on improving the microflora diversity, particularly in increasing the abundance of Lactococcus significantly. Thus, as an endophyte, Lactococcus plays an important role in E. prostrata modulating intestinal tract. Our study suggested that endophytes of Chinese herbal medicines might be a novel target for the treatment of diseases by regulating the GM.

经鼻滴入海人藻酸引起C_(57)BL/6小鼠嗅球和海马区神经元的退行性病变

目的 应用海人藻酸 (KA)在C57BL/ 6小鼠建立神经退行性病变动物模型并观察其对嗅球神经元的影响。方法 经鼻滴入KA应用尼氏和嗜银染色观察海马及嗅球的病理变化 ,免疫组化检测Cyclooxygenase 2 (COX 2 )的表达。结果 经鼻滴入KA成功地在C57BL/ 6小鼠建立了神经退行性病变动物模型 ,KA通过嗅神经引起双侧嗅球和海马损伤 ,其病变程度与小鼠体重和滴入KA剂量有关 ,同时KA引起了脑内明显的胶质细胞增生和炎症因子COX 2在嗅球部的表达。

C_(57)BL/6无毛小鼠皮肤组织学研究

目的：观察Ｃ５７ＢＬ／６无毛小鼠皮肤组织学结构。方法：１０％甲醛固定，行石蜡切片，ＨＥ染色。结果：动物表皮有一层角化过度的角质层，毛干消失，毛球结构不正常，毛囊内为一些角化物质，有的变为空囊腔。真皮深层及皮下组织内含有大量黑色素细胞，并有树突状突起。结论：Ｃ５７ＢＬ／６无毛小鼠真皮深层及皮下组织内含有大量黑色素细胞，可用于黑色素沉着疾病及黑色素瘤的研究。

Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

Establishment of Germ-line Competent C57BL/6J Embryonic Stem Cell Lines

Objective To establish C57BL/6J embryonic stem （ES） cell lines with potential germ- line contribution Methods ES cells were isolated from blastocyst inner cell mass of C5 7BL/6J mice, and cultured for 15 passages, and then injected into blastococels of ICR mice blastocysts to establish chimeric mice. Results Three ES cell lines （mC57ES1,mC57ES3, mC57ES7） derived from the inner cell mass of C57BL/6J mice blastocysts were established. They were characteristic of undifferentiated state, including normal XY karyotype, expression of a specific cell surface marker “stage-specific embryonic antigen-I” and alkaline phosphatase in continuous passage. When injected into immunodeficient mice, mC57ES1 cells consistently differentiated into derivatives of all three embryonic germ layers. When mC57ES1 cells were transferred into ICR mice blastocysts, 4 chimeric mice have been obtained. One male of them revealed successful germ-line transmission. Conclussion We have obtained C57BL/6J ES cell lines with a potential germ-line contribution, which can be used to generate transgenic and gene knock-out mice.

Short-lived AIM2 Inflammasome Activation Relates to Chronic MCMV Infection in BALB/c Mice

Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of disseminated murine cytomegalovirus(MCMV)infection in BALB/c and C57BL/6 mice,we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication,trying tofigure out whether AIM2 inflammasome is related to the chronic mechanism of MCMV.BALB/c and C57BL/6 mice were sacrificed on day 0,1,3,7,14 and 28 post infection.Expression levels of AIM2,pro-caspase-1,caspase-1 p20,pro-IL1β and mature IL1β in primary peritoneal macrophages(PMs)and spleens were detected by Western blotting.Contents of IL18 in the serum were detected by ELISA.Pathological examinations of livers were performed,and mRNA levels of MCMV glycoprotein B(gB)in salivary glands also assessed.Results showed that expression levels of AIM2 in PMs and spleens of C57BL/6 mice increased on day 3,even continued to day 28;caspase-1 p20 and mature IL1β increased on day 7,14 and 28;the persistently high expression of IL1β in the serum started on day 1,showing a double peak curve.As for BALB/c mice,expression of AIM2 in PMs increased on day 1 and day 7,while contents of AIM2 in spleens increased on day 1 and day 3;caspase-1 p20 and mature ILip merely increased 7 days fter infection.Thereafter,expression levels of AIM2,caspase-1 p20,mature IL1β and IL18 were limited;the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in C57BL/6 mice.The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to MCMV.In conclusion,the activation of AIM2 inflammasome in BALB/c mice was short-lived,which is quite possibly related to the chronicity of MCMV infection.

Gut Microbiota Reconstruction Following Host Infection with Bloodstage Plasmodium berghei ANKA Strain in a Murine Model

Malaria remains a global health problem.The relationship between Plasmodium spp.and the gut microbiota as well as the impact of Plasmodium spp.on the gut microbiota in vertebrate hosts is unclear.The aim of the current study was to evaluate the effect of blood-stage Plasmodium parasites on the gut microbiota of mice.The gut microbiota was analyzed by 16S rRNA sequencing and bioinformatic analyses at three stages.The gut microbiota changed during the three phases:the healthy stage,the infection stage,and the cure stage(on the 9th day after malarial elimination).Moreover,the gut microbiota of these infected animals did not recover after malaria infection.There were 254 operational taxonomic units(OTUs)across all three stages,and there were unique strains or OTUs at each stage of the experiment.The percentages of community abundance of 8 OTUs changed significantly(P<0.05).The dominant OTU in both the healthy mice and the mice with malaria was OTU265,while that in the cured mice was OTU234.In addition,the changes in OTU147 were the most noteworthy.Its percentage of community abundance varied greatly,with higher values during malaria than before malaria infection and after malaria elimination.These results indicated that the external environment influenced the gut microbiota after host C57BL/6 mice were infected with blood-stage P.berghei ANKA and that the same was true during and after elimination of blood-stage P.berghei ANKA.In addition,we could not isolate OTU147 for further study.This study identified gut microbiota components that were reconstructed after infection by and elimination of blood-stage P.berghei ANKA in host C57BL/6 mice,and this process was affected by P.berghei ANKA and the external environment of the host.

Characteristics of gut microbiota in representative mice strains:Implications for biological research

Background:Experimental animals are used to study physiological phenomena,pathological mechanisms,and disease prevention.The gut microbiome is known as a potential confounding factor for inconsistent data from preclinical studies.Although many gut microbiome studies have been conducted in recent decades,few have focused on gut microbiota fluctuation among representative mouse strains.Methods:A range of frequently used mouse strains were selected from 34 isolation packages representing disease-related animal(DRA),immunity defect animal(IDA),or gene-editing animal(GEA)from the BALB/c and C57BL/6J backgrounds together with normal mice,and their microbial genomic DNA were isolated from mouse feces to sequence for the exploration of gut microbiota.Results:Mouse background strain,classification,introduced source,introduced year,and reproduction type significantly affected the gut microbiota structure(p<0.001 for all parameters),with background strain contributing the greatest influence(R^(2)=0.237).In normal groups,distinct gut microbiota types existed in different mouse strains.Sixty-four core operational taxonomic units were obtained from normal mice,and 12 belonged to Lactobacillus.Interestingly,the gut microbiota in C57BL/6J was more stable than that in BALB/c mice.Furthermore,the gut microbiota in the IDA,GEA,and DRA groups significantly differed from that in normal groups(p<0.001 for all).Compared with the normal group,there was a significantly higher Chao 1 and Shannon index(p<0.001 for all)in the IDA,GEA,and DRA groups.Markedly changed classes occurred with Firmicutes and Bacteroidetes.The abundances of Helicobacter,Blautia,Enterobacter,Bacillus,Clostridioides,Paenibacillus,and Clostridiales all significantly decreased in the IDA,GEA,and DRA groups,whereas those of Saccharimonas,Rikenella,and Odoribacter all significantly increased.

Verification of Lactobacillus brevis tolerance to simulated gastric juice and the potential effects of postbiotic gamma-aminobutyric acid in streptozotocin-induced diabetic mice

The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.0373) strains as glutamic acid decarboxylase 65(GAD65)carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in vivo.PCR amplification of gad and in vitro i.e.,(growth rate,viability at different pH,bile tolerance,and survivability in simulated gastric juice)were performed.In vivo experiments were conducted in 7 groups of C57BL/6J mice.Each group was injected with streptozotocin(Cont_(STZ),INSSTZ,LAC1_(STZ),LAC_(1MFDSTZ),LAC_(2STZ),LAC_(2MFDSTZ))daily except for the control(Cont).One group was injected with insulin(INSSTZ).The body weight and hyperglycemia in the blood were assessed weekly,post-euthanasia blood plasma parameters,insulin,and histological examination were evaluated.Results indicated L.brevis strains demonstrated a great tolerance to bile and simulated gastric juice in vitro(P<0.05).Cont_(STZ) had the highest average glucose level(6.84±6.46)mmol/L while INS_(STZ) expressed dramatically decreed in glucose level and displayed a significant decline in the average of weekly blood glucose(−5.74±3.08)mmol/L.The lowest body weight(ContSTZ)was(19.30±0.25)g.Based on the blood plasma analysis,L.brevis strains improved good cholesterol properties,liver and kidney functions,where most of these parameters fall within the average the reference range and prevent the development of symptoms of type 1 diabetes in vivo.As recommended,L.brevis should be commonly distributed as a postbiotic GABA in pharmaceutical and nutritional applications.

Different coding characteristics between flight and freezing in dorsal periaqueductal gray of mice during exposure to innate threats

Background:Flight and freezing are two vital defensive behaviors that mice display to avoid natural enemies.When they are exposed to innate threats,visual cues are processed and transmitted by the visual system into the emotional nuclei and finally transmitted to the periaqueductal gray(PAG)to induce defensive behaviors.However,how the dorsal PAG(dPAG)encodes the two defensive behaviors is unclear.Methods:Multi-array electrodes were implanted in the dPAG nuclei of C57BL/6 mice.Two kinds of visual stimuli(looming and sweeping)were used to induce defensive behaviors in mice.Neural signals under different defense behaviors were recorded,and the encoding characteristics of the two behaviors were extracted and analyzed from spike firing and frequency oscillations.Finally,synchronization of neural activity during the defense process was analyzed.Results:The neural activity between flight and freezing behaviors showed different firing patterns,and the differences in the inter-spike interval distribution were mainly reflected in the 2–10 ms period.The frequency band activities under both defensive behaviors were concentrated in the theta band;the active frequency of flight was~8to 10 Hz,whereas that of freezing behavior was~6 to 8 Hz.The network connection density under both defense behaviors was significantly higher than the period before and after defensive behavior occurred,indicating that there was a high synchronization of neural activity during the defense process.Conclusions:The dPAG nuclei of mice have different coding features between flight and freezing behaviors;during strong looming stimulation,fast neuro-i nstinctive decision making is required while encountering weak sweeping stimulation,and computable planning late behavior is predicted in the early stage.The frequency band activities under both defensive behaviors were concentrated in the theta band.There was a high synchronization of neural activity during the defense process,which may be a key factor triggering different defensive behaviors.

Dietary Nε-(carboxymethyl)lysine affects cardiac glucose metabolism and myocardial remodeling in mice

BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered associated with myocardial remodeling.Nε-(carboxymethyl)lysine(CML)is a representative foodborne toxic product,which can be ingested via daily diet.Therefore,there is a marked need to explore the effects of dietary CML on the myocardium.AIM To explore the effects of dietary CML(dCML)on the heart.METHODS C57 BL/6 mice were divided into a control group and a dCML group.The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk.Body weight and blood glucose were recorded every 4 wk.^(18)F-fluorodeoxyglucose(FDG)was used to trace the glucose uptake in mouse myocardium,followed by visualizing with micro-positron emission tomography(PET).Myocardial remodeling and glucose metabolism were also detected.In vitro,H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h.The effects of exogenous CML on glucose metabolism,collagen I expression,hypertrophy,and apoptosis of cardiomyocytes were analyzed.RESULTS Our results suggest that the levels of fasting blood glucose,fasting insulin,and serum CML were significantly increased after 20 wk of dCML.Micro-PET showed that ^(18)F-FDG accumulated more in the myocardium of the dCML group than in the control group.Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy.The indexes of myocardial fibrosis,apoptosis,and hypertrophy were also increased in the dCML group,whereas the activities of glucose metabolism-related pathways and citrate synthase(CS)were significantly inhibited.In cardiomyocytes,collagen I expression and cellular size were significantly increased after the addition of exogenous CML.CML significantly promoted cellular hypertrophy and apoptosis,while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.CONCLUSION This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.