电针对APP/PS1转基因小鼠海马低密度脂蛋白受体相关蛋白-1及其mRNA表达的影响

目的:研究电针是否是通过影响LRP1mRNA水平、提高LRP1的表达,从而促进脑内Aβ清除。方法:将4月龄APP/PS1转基因鼠,随机分为模型组、电针治疗组,以同窝同背景转基因阴性小鼠为正常对照组。电针干预"涌泉"、"百会"0.1 m A,15 min/次,隔日1次,治疗6周。治疗后,以免疫组化法观察脑组织LRP1阳性表达,以Western blotting法检测海马LRP1表达,以Real-time PCR法检测海马LRP1mRNA表达。结果:LRP1表达于脑微血管内皮细胞、胶质细胞、神经元等处。模型组海马LRP1蛋白、LRP1mRNA相对表达量低于正常对照组(P<0.05),电针治疗组海马LRP1及LRP1mRNA比模型组有上升趋势,但差异无统计学意义(P>0.05)。结论:电针干预可能影响5月龄APP/PS1转基因小鼠海马内所有细胞LRP1及LRP1mRNA表达,可能是电针干预AD发病的潜在靶点,但实验方案还需进一步完善。

Design and implementation of low-cost geomagnetic field monitoring equipment for high-density deployment

The observation of geomagnetic field variations is an important approach to studying earthquake precursors.Since 1987,the China Earthquake Administration has explored this seismomagnetic relationship.In particular,they studied local magnetic field anomalies over the Chinese mainland for earthquake prediction.Owing to the years of research on the seismomagnetic relationship,earthquake prediction experts have concluded that the compressive magnetic effect,tectonic magnetic effect,electric magnetic fluid effect,and other factors contribute to preearthquake magnetic anomalies.However,this involves a small magnitude of magnetic field changes.It is difficult to relate them to the abnormal changes of the extremely large magnetic field in regions with extreme earthquakes owing to the high cost of professional geomagnetic equipment,thereby limiting large-scale deployment.Moreover,it is difficult to obtain strong magnetic field changes before an earthquake.The Tianjin Earthquake Agency has developed low-cost geomagnetic field observation equipment through the Beijing–Tianjin–Hebei geomagnetic equipment test project.The new system was used to test the availability of equipment and determine the findings based on big data..

High density dislocations enhance creep ageing response and mechanical properties in 2195 alloy sheet

The creep strain of conventionally treated 2195 alloy is very low,increasing the difficulty of manufacturing Al-Cu-Li alloy sheet parts by creep age forming.Therefore,finding a solution to improve the creep formability of Al-Cu-Li alloy is vital.A thorough comparison of the effects of cryo-deformation and ambient temperature large pre-deformation(LPD)on the creep ageing response in the 2195 alloy sheet at 160℃with different stresses has been made.The evolution of dislocations and precipitates during creep ageing of LPD alloys are revealed by X-ray diffraction and transmission electron microscopy.High-quality 2195 alloy sheet largely pre-deformed by 80%without edge-cracking is obtained by cryo-rolling at liquid nitrogen temperature,while severe edge-cracking occurs during room temperature rolling.The creep formability and strength of the 2195 alloy are both enhanced by introducing pre-existing dislocations with a density over 1.4×10^(15)m^(−2).At 160℃and 150 MPa,creep strain and creep-aged strength generally increases by 4−6 times and 30−50 MPa in the LPD sample,respectively,compared to conventional T3 alloy counterpart.The elongation of creep-aged LPD sample is low but remains relevant for application.The high-density dislocations,though existing in the form of dislocation tangles,promote the formation of refined T1 precipitates with a uniform dispersion.

一种新型低功耗异步比较器的设计方法

本文利用输入数据的统计特性,设计了两种低功耗异步比较器——异步行波比较器和提前终止异步比较器.异步行波比较器从第一个不相等的数位开始停止运算,但要把结果传到最低位,消耗部分功耗.提前终止异步比较器通过修改真值表,基于新的比较单元电路和终止判断电路,在第一个不相等的数位停止运算并立即输出比较结果,节省不必要的功耗.新设计的异步比较器和用于对比的同步比较器(BCL比较器和门控时钟比较器)均用SMIC0.18μm工艺实现.仿真结果表明,提前终止异步比较器功耗最低,与同步BCL比较器和门控时钟比较器相比,在随机数据和来自LDPC解码器的数据下,分别节省了87.1%、84.5%和37.5%、28.6%的功耗.

The Effects of Apolipoprotein E Polymorphism on Serum Lipids, Lipoproteins and Apolipoproteins Variation

Objective: To study the effects of Apolipoprotein E (ApoE) polymorphism onserum levels of lipids, lipoproteins and apolipoproteins. Methods: Fragments of ApoE gene forthex-on containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested untilCfo I endonuclease. Genotypes and alleles frequencies of 168 healthy persons in Jiangsu area werecalculated. The effects of ApoE genotypes and alleles on serum lipids, lipoproteins andapolipoproteins variation were analyzed. Results: The effects of ApoE alleles on total cholesterol(TC), law density lipoprotein-cholesterol (LDL-C), ApoB was: along a decreasing gradientε_4>ε_3>ε_2. The effect of ε_4 allele was to increase serum levels of TC, LDL-C and ApoB, andthe ε_2 allele had an effect opposite to that of ε_4 allele. Conclusion: ApoE polymorphism is anindependent genetic factor on individual serum levels of lipids and apolipoproteins.

Improved parallel weighted bit-flipping algorithm

An improved parallel weighted bit-flipping（PWBF） algorithm is presented. To accelerate the information exchanges between check nodes and variable nodes, the bit-flipping step and the check node updating step of the original algorithm are parallelized. The simulation experiments demonstrate that the improved PWBF algorithm provides about 0. 1 to 0. 3 dB coding gain over the original PWBF algorithm. And the improved algorithm achieves a higher convergence rate. The choice of the threshold is also discussed, which is used to determine whether a bit should be flipped during each iteration. The appropriate threshold can ensure that most error bits be flipped, and keep the right ones untouched at the same time. The improvement is particularly effective for decoding quasi-cyclic low-density paritycheck（QC-LDPC） codes.

Performance analysis of coded OFDM systems using a novel class of LDPC codes

A new method of constructing regular low-density parity-check (LDPC) codes was proposed. And the novel class of LDPC codes was applied in a coded orthogonal frequency division multiplexing (OFDM) system. This method extended the class of LDPC codes which could be constructed from shifted identity matrices. The method could avoid short cycles in Tanner graphs with simple inequation in the construction of shifting identity matrices, which made the girth of Tanner graphs 8. Because of the quasicyclic structure and the inherent block configuration of parity-check matrices, the encoders and the decoders were practically feasible. They were linear-time encodable and decodable. The LDPC codes proposed had various code rates, ranging from low to high. They performed excellently with iterative decoding and demonstrate better performance than other regular LDPC codes in OFDM systems.

Modified Benes network architecture for WiMAX LDPC decoder

A modified Benes network is proposed to be used as an optimal shuffle network in worldwide interoperability for microwave access （WiMAX） low density parity check （LDPC） decoders, When the size of the input is not a power of two, the modified Benes network can achieve the most optimal performance. This modified Benes network is non-blocking and can perform any sorts of permutations, so it can support 19 modes specified in the WiMAX system. Furthermore, an efficient algorithm to generate the control signals for all the 2 × 2 switches in this network is derived, which can reduce the hardware complexity and overall latency of the modified Benes network. Synthesis results show that the proposed control signal generator can save 25.4% chip area and the overall network latency can be reduced by 36. 2%.

一种新的LDPC译码算法

由于LDPC码的优良性能,因此在信息可靠传输中有良好的应用前景。本文提出了一种将BP算法和基于列表的SIHO(软输入硬输出)算法相结合的译码算法,通过与BP、MLD算法的误码率性能和译码复杂度比较,本算法复杂度比MLD有明显降低,而在性能上优于BP算法并接近MLD译码算法。

Wnt signaling control of bone cell apoptosis

Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled （FZD） G-protein-coupled receptor and a low-density lipoprotein （LDL） receptor-related protein （LRP）. The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density （BMD） and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects ofosteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-l, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3β support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.

一种CCSDS深空标准的LDPC码高效实现

针对CCSDS(空间数据系统咨询委员会)深空通信标准LDPC(低密度奇偶校验码),为减少定点量化后的译码性能损失,提出了一种改进的译码修正算法。通过分析矩阵结构特点,并引入交错译码结构以及流水结构,设计了一种适合该标准深空通信LDPC码编译码器的高效实现结构。使用此结构,在Xilinx公司的XC5VSX95T芯片上实现了CCSDS深空通信标准的(8 192,4 096)LDPC码,在40次迭代情况下可以达到47m的吞吐率。实践表明:该设计可以灵活地移植应用于其他码率的CCSDS深空通信标准LDPC编译码器设计。

Efficient construction and encoding of QC-LDPC codes by cyclic lifting of protographs

Quasi-cyclic low-density parity-check （QC-LDPC） codes can be constructed conveniently by cyclic lifting of protographs. For the purpose of eliminating short cycles in the Tanner graph to guarantee performance, first an algorithm to enumerate the harmful short cycles in the protograph is designed, and then a greedy algorithm is proposed to assign proper permutation shifts to the circulant permutation submatrices in the parity check matrix after lifting. Compared with the existing deterministic edge swapping （DES） algorithms, the proposed greedy algorithm adds more constraints in the assignment of permutation shifts to improve performance. Simulation results verify that it outperforms DES in reducing short cycles. In addition, it is proved that the parity check matrices of the cyclic lifted QC-LDPC codes can be transformed into block lower triangular ones when the lifting factor is a power of 2. Utilizing this property, the QC- LDPC codes can be encoded by preprocessing the base matrices, which reduces the encoding complexity to a large extent.

Berberine promotes the development of atherosclerosis and foam cell formation by inducing scavenger receptor A expression in macrophage

Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotcin E-deficient （apoE^-/-） mice was investigated. In apoE^-/- mice, berberine induced in rivo foam cell formation and promoted atheroselerosis development. The foam cell formation induced by berberinc was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A （SR-A） expression in macrophages, berberine increased the uptake of modified LDL （DiO-Ac-LDL）. Bcrberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A expression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the ceils involved in atherosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.

Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL receptor-deficient mice

Background Hyperhomocysteine is an independent risk factor of coronary heart disease （CHD）. However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the forma tion of atherosclerosis in low-density lipoprotein receptor-deficient （LDLr ） mice. Methods Forty-eight 7-week-old LDLr/ mice were assigned to the following groups： mice fed a standard rodent diet （control group）, mice fed a high-methionine diet （high-methionine group）, mice fed a high-fat diet （high-fat group）, and mice fed a diet high in both methionine and fat （high-methionine and high-fat group）. At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLrmice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.

Metabolic syndrome and gallstone disease

AIM： To investigate the association between metabolic syndrome （NetS） and the development of gallstone disease （GSD）. METHODS： A cross-sectional study was conducted in 7570 subjects （4978 men aged 45.0：1：8.8 years, and 2592 women aged 45.3：1：9.5 years） enrolled from the physical check-up center of the hospital. The subjects included 918 patients with gallstones （653 men and 265 women） and 6652 healthy controls （4325 men and 2327 women） without gallstones. Body mass index （BII）, waist circumference, blood pressure, fasting plasma glucose （FPG） and serum lipids and lipoproteins levels were measured. Colorimetric method was used to measure cholesterol, high-density lipoprotein cho- lesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）. Dextrose oxidizing enzyme method was used to measure FPG. Subjects were asked to complete a questionnaire that enquired about the information on demographic data, age, gender, histories of diabetes mellitus, hypertension, and chronic liver disease and so on. Metabolic syndrome was diagnosed according to the Adult Treatment Panel HI （ATP ]3） criteria. Gall- stones were defined by the presence of strong intralu- minal echoes that were gravity-dependent or attenu- ated ultrasound transmission. RESULTS： Among the 7570 subjects, the prevalence of the gallstone disease was 12.1% （13.1% in men and 10.2% in women）. BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose and serum triglyceride （TG） in cases group were higher than in controls, while serum high-density lipid was lower than in controls. There were significant differences in the waist circumference, blood pressure, FPG and TG between cases and controls. In an age- adjusted logistic regression model, metabolic syndrome was associated with gallstone disease. The age-adjust- ed odds ratio of MetS for GSD in men was 1.29 [95% confidence interval （CI）, 1.09-1.52; P = 0.0030], and 1.68 （95% CI, 1.26-2.25; P = 0.0004） in women; the overall age-adjusted odds ratio of NetS for GSD was 1.42 （95% CI, 1.23-1.64; P 〈 0.0001）. The men with more metabolic disorders had a higher prevalence of gallstone disease, the trend had statistical significance （P 〈 0.0001）. The presence of 5 components of the MetS increased the risk of gallstone disease by 3.4 times （P 〈 0.0001）. The prevalence of GSD in women who had 5 components of NetS was 5 times higher than in those without Nets component. The more the components of Mets, the higher the prevalence of GSD （P 〈 0.0001）. The presence of 5 components of the Mets increased the risk of gallstone disease by 4.0 times. CONCLUSION： GSD appears to be strongly associated with MetS, and the more the components of NetS, the higher the prevalence of GSD.

Yi-Qi-Zeng-Min-Tang,a Chinese medicine,ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.

Inhibitory Effect of Isorhapontigenin on Copper-Mediated Peroxidation of Human Low-Density Lipoprotein in vitro

Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.

A practical approach to the diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis is a disease characterized by specific pathological features,different from those of other forms of pancreatitis,that responds dramatically to steroid therapy.The pancreatic parenchyma may be diffusely or focally involved with the possibility of a low-density mass being present at imaging,mimicking pancreatic cancer.Clinically,the most relevant problems lie in the diagnosis of autoimmune pancreatitis and in distinguishing autoimmune pancreatitis from pancreatic cancer.Since in the presence of a pancreatic mass the probability of tumour is much higher than that of pancreatitis,the physician should be aware that in focal autoimmune pancreatitis the first step before using steroids is to exclude pancreatic adenocarcinoma.In this review,we briefly analyse the strategies to be followed for a correct diagnosis of autoimmune pancreatitis.

Hepatic focal nodular hyperplasia in children:Imaging features on multi-slice computed tomography

AIM:To retrospectively analyze the imaging features of hepatic focal nodular hyperplasia(FNH) in children on dynamic contrast-enhanced multi-slice computed tomography(MSCT) and computed tomography angiography(CTA) images.METHODS:From September 1999 to April 2012,a total of 218 cases of hepatic FNH were confirmed by either surgical resection or biopsy in the Sun Yat-sen Memorial Hospital of Sun Yat-sen University and the Cancer center of Sun Yat-sen University,including 12 cases(5.5%) of FNH in children(age ≤ 18 years old).All the 12 pediatric patients underwent MSCT.We retrospectively analyzed the imaging features of FNH lesions,including the number,location,size,margin,density of FNH demonstrated on pre-contrast and contrastenhanced computed tomography(CT) scanning,central scar,fibrous septa,pseudocapsule,the morphology of the feeding arteries and the presence of draining vessels(portal vein or hepatic vein).RESULTS:All the 12 pediatric cases of FNH had solitary lesion.The maximum diameter of the lesions was 4.0-12.9 cm,with an average diameter of 5.5 ± 2.5 cm.The majority of the FNH lesions(10/12,83.3%) had well-defined margins.Central scar(10/12,83.3%) and fibrous septa(11/12,91.7%) were commonly found in children with FNH.Central scar was either isodense(n = 7) or hypodense(n = 3) on pre-contrast CT images and showed progressive enhancement in 8 cases in the equilibrium phase.Fibrous septa were linear hypodense areas in the arterial phase and isodense in the portal and equilibrium phases.Pseudocapsule was very rare(1/12,8.3%) in pediatric FNH.With the exception of central scars and fibrous septa within the lesions,all 12 cases of pediatric FNH were homogenously enhanced on the contrast-enhanced CT images,significantly hyperdense in the arterial phase(12/12,100.0%),and isodense in the portal venous phase(7/12,58.3%) and equilibrium phase(11/12,91.7%).Central feeding arteries inside the tumors were observed on CTA images for all 12 cases of FNH,whereas no neovascularization of malignant tumors was noted.In 9 cases(75.0%),there was a spoke-wheel shaped centrifugal blood supply inside the tumors.The draining hepatic vein was detected in 8 cases of pediatric FNH.However,the draining vessels in the other 4 cases could not be detected.No associated hepatic adenoma or hemangioma was observed in the livers of the 12 pediatric cases.CONCLUSION:The characteristic imaging appearances of MSCT and CTA may reflect the pathological and hemodynamic features of pediatric FNH.Dynamic multi-phase MSCT and CTA imaging is an effective method for diagnosing FNH in children.

Liraglutide reduces oxidized LDL-induced oxidative stress and fatty degen- eration in Raw 264.7 cells involving the AMPK/SREBP1 pathway

Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.