OBJECTIVES: The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. METHODS: Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. RESULTS: The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. CONCLUSIONS: The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.
Aged ; Apolipoproteins E/*genetics ; Cognition/physiology ; Cognition Disorders/etiology/*genetics ; Female ; Humans ; Korea ; Male ; Polymorphism, Genetic

Brain injury is a kind of wound by violence on head, which is a mechanical distortion of skull, meninx, cerebral vascular and brain tissue due to outside force acting on head. Apolipoproteins E (ApoE) is a major kind of apolipoproteins, participating in the metabolism of lipid and regulating balance of cholesterol. Some recent investigations show that gene polymorphism of ApoE is associated with various kinds of diseases. Also its immunoreactivity is changed regularly with brain injury. In addition, ApoE has remarkable effect in neurological normal growth and reparative process after brain injury. This article reviews the biological characteristics and mechanism of ApoE in the repair of brain injury and application prospect in forensic medicine, which may be able to provide new ideas for estimation of the brain injury time and related experimental research.
Apolipoproteins E/physiology* ; Brain/metabolism* ; Brain Injuries/physiopathology* ; Forensic Medicine ; Head ; Humans ; Polymorphism, Genetic

OBJECTIVETo observe the effect of Maixinkang Capsule (MXK) on Ca2t concentration and mitochondrial membrane potential in liver cells of ApoE(-/-) mice.

METHODSLiver cells from ApoE(-/-) mice were separated using collagenase digestive method. After the primary cells were cultured for 8 days in vitro, the concentration of 10% MXK contained rat's serum was added into the culture fluid. The Ca2+ concentration and mitochondrial membrane potential in liver cells after 48-hr culture were measured by confocal laser scanning microscopy with Flou-3 and Jc-1 as probes.

RESULTSMXK could decrease Ca2+ concentration in liver cells, which was significantly different to that in the control group (P < 0.01). Meanwhile, MXK could significantly improve mitochondrial membrane potential in liver cells (P < 0.01). There was no obvious dose-effect relationship shown in both effects of MXK.

CONCLUSIONMXK can decrease Ca2+ concentration and improve the mitochondrial membrane potential in liver cells of ApoE(-/-) mice so as to regulate the lipids and prevent the occurrence and development of hyperlipemia and atherosclerosis.

Animals ; Animals, Newborn ; Apolipoproteins E ; genetics ; Calcium Channels ; drug effects ; Hepatocytes ; physiology ; Membrane Potentials ; Mice ; Mice, Knockout ; Mitochondrial Membranes ; physiology

Apolipoproteins E ; genetics ; physiology ; Cholesterol 7-alpha-Hydroxylase ; genetics ; Cholesterol, LDL ; genetics ; Coronary Disease ; genetics ; Genetic Predisposition to Disease ; genetics ; Genetic Variation ; Humans ; Polymorphism, Genetic

OBJECTIVETo observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice.

METHODSFour, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected.

RESULTSCompared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P < 0.01); levels of TC, TG, LDL-C increased, and HDL-C level decreased in 12- and 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01); the proportion of Mo increased in 4-week-old apoE(-/-) mice (P < 0.05); proportions of Mo and Ly6c(hi) increased in 8-week-old apoE(-/-) mice (P < 0.05). Compared with the blank control group, levels of TC, TG, and LDL-C, proportions of Mo and Ly6c(hi) increased (P < 0.01, P < 0.05), but HDL-C level decreased (P <0. 01) in the control group after intervention. Compared with the control group, body weight gained less in the Western medicine group and the Chinese medicine group (P < 0.05); the proportion of Ly6c(hi) subtype decreased in the Chinese medicine group (P < 0.05).

CONCLUSIONSIn development process blood lipids levels in apoE(-/-) mice are not only associated with age. Blood lipids levels induced growth changes in natural immune system are also correlated with age. In early stage of lipids development HJD intervention could correct this special immune disorder in apoE(-/-) mice.

Animals ; Apolipoproteins E ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Knockout Techniques ; Hyperlipidemias ; Lipids ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes ; physiology

OBJECTIVE: To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS). METHODS: Fourteen apolipoprotein E-deficient (ApoE^-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE^-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot. RESULTS: Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE^-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE^-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05). CONCLUSION Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.
Mice ; Animals ; Apelin ; Tissue Plasminogen Activator/metabolism* ; Quercetin/therapeutic use* ; AMP-Activated Protein Kinases/metabolism* ; Sirtuin 1/metabolism* ; Signal Transduction/physiology* ; Atherosclerosis/metabolism* ; Apolipoproteins E

Atopic dermatitis (AD) is an inflammatory skin disorder that is both uncomfortable and distressing to patients, and its prevalence has been steadily increasing. It is obvious that the identification of efficient markers of AD in plasma would offer the possibility of effective diagnosis, prevention, and treatment strategies. In this study, a proteomic approach was used to analyze plasma glycoproteins from both children with AD and healthy child donors. Several protein spots showing significant quantitative changes in the AD patients were identified. Through sequential studies, it was confirmed that CD5L and ApoE were significantly up-regulated or down-regulated, respectively, in the plasma from AD patients compared with that from healthy donors. In addition, we suggest that the up-regulated CD5L in AD patients causes eosinophilia by inhibiting apoptosis or promoting the proliferation of eosinophils either in combination with or without IL-5. The glycoproteomic data in this study provides clues to understanding the mechanism of atopic alterations in plasma and suggests AD-related proteins can be used as candidate markers for AD.
Apolipoproteins E/*blood ; Biological Markers/blood ; Cell Line ; Cell Proliferation ; Child ; Dermatitis, Atopic/*metabolism ; Eosinophilia/metabolism ; Eosinophils/physiology ; Female ; Glycoproteins/*blood ; Humans ; Interleukin-5/metabolism ; Male ; Proteomics ; Scavenger Receptors, Class B/*blood

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.
Animals ; Apolipoproteins E/genetics/physiology ; Atherosclerosis/*drug therapy ; Cytokines/metabolism ; Disease Models, Animal ; Drug Synergism ; Ginkgo biloba/*chemistry ; Humans ; Macrophages/cytology/drug effects ; Male ; Mice ; Mice, Nude ; Plant Extracts/*administration & dosage/chemistry ; Reactive Oxygen Species/*metabolism ; Tetrazoles/*administration & dosage

OBJECTIVETo study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice.

METHODSThirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n = 18) and control group (n = 14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root (1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-alpha were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section.

RESULTSThe amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-alpha in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group.

CONCLUSIONRosiglitazone suppresses the expression of tumor necrosis factor-alpha, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.

Animals ; Aorta ; pathology ; Apolipoproteins E ; genetics ; physiology ; Atherosclerosis ; blood ; pathology ; prevention & control ; Blood Glucose ; analysis ; Body Weight ; drug effects ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Female ; Hypoglycemic Agents ; therapeutic use ; Macrophages ; pathology ; Male ; Mice ; Mice, Knockout ; Thiazolidinediones ; therapeutic use ; Tumor Necrosis Factor-alpha ; biosynthesis

OBJECTIVETo observe the regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase-9 (MMP-9) in aorta of apolipoprotein E gene knocked-out (ApoE (-/-)) mice.

METHODSApoE (-/-) mice of 13-week old were divided into two groups and fed with normal diet (Group A) and hyperlipidemic diet (Group B) respectively, the latter was subdivided into 7 groups as Group B1 - 7. Besides, a normal control group was set up with C57BL/6J mice. The drugs used for intervention were polydatin (PD, with 26.6 mg/kg as one dose) for detoxifying and Xiongshao Capsule (XC, with 110 mg/kg as one dose) for activating blood circulation respectively. The intervention was started 19 weeks later by treated Group B1 with PD one dose daily, Group B2 with XC one dose daily, Group B3 with PD and XC each 2 doses daily, Group B4 with PD and XC each one dose daily, Group B5 with PD and XC each half dose daily, Group B6 with lovastatin. To the Group B 7 (as a hyperlipidemia model group) as well as Group A and the normal control group, normal saline was given. After 17 weeks of intervention, the expressions of NF-kappaB and MMP-9 in aorta of mice were determined with immunohistochemical assay.

RESULTSExpressions of NF-kappaB and MMP-9 in aorta and sclerotic plaque were higher in group B7 than those in the normal control group, which were lowered in group B1 - 6 (P < 0.01), and the optimal effect was shown in group B3 (P <0.01).

CONCLUSIONCombined use of Chinese herbal medicine for detoxifying and activating blood circulation could reduce expression of NF-kappaB and MMP-9 in aorta of ApoE (-/-) mice, and the effect of the combination of the two was superior to that of use either of them.

Animals ; Anticholesteremic Agents ; pharmacology ; Aorta ; drug effects ; metabolism ; physiology ; Apolipoproteins E ; genetics ; Blood Flow Velocity ; drug effects ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Lovastatin ; pharmacology ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular ; blood supply ; drug effects ; metabolism ; NF-kappa B ; biosynthesis