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

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

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 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

BACKGROUND/AIMS: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. METHODS: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. RESULTS: The epsilon3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the epsilon2, epsilon3, and epsilon4 alleles, respectively. Significantly more of those patients carrying the epsilon3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. CONCLUSIONS: The ApoE epsilon3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.
Adult ; Aged ; Aged, 80 and over ; Alleles ; Apolipoproteins E/*genetics/metabolism ; Carcinoma, Hepatocellular/*metabolism/pathology ; Case-Control Studies ; Child ; Chronic Disease ; Cohort Studies ; Female ; Gene Frequency ; Genotype ; Hepatitis B/complications/metabolism/virology ; Hepatitis B virus/*physiology ; Humans ; Liver Cirrhosis/etiology/*metabolism ; Liver Neoplasms/*metabolism/pathology ; Male ; Middle Aged ; Young Adult

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 investigate the influence of endothelial dysfunction induced by inoculated dendritic cells (DCs) loaded heat shock protein 60 (HSP60) in apolipoprotein (Apo) E-null mice, and the effect of Puerarin on it.

METHODSHSP60 DC (DChsp) acquired after prepared bone marrow-derived DCs of ApoE-null mice and treated with HSP60. In vitro, the function of DCs and the effect of Puerarin were detected. While in vivo, ApoE-null mice fed with high-cholesterol forage were divided into two groups and intravenous inoculated with DCh-sp or normal saline via vein twice respectively. The mice in the two groups were subdivided into the Puerarin group and non-treated group, and they were injected intraperitoneally with Puerarin and normal saline at the beginning of inoculation and the following 3 weeks, respectively. In addition, C57BL/6 mice without inoculation were taken as the normal control group. Two weeks after the last time inoculated, the response of T lymphocytes to HSP60 and endothelial-dependent diastolic function of aortic ring were detected.

RESULTSHSP60 could promote DCs expressed CD86 and stimulate T lymphocytes proliferation in vitro, while Puerarin had significantly inhibitory effect. After inoculated, DChsp activated inflammatory response in vivo and aggravated endothelium-dependent dilation in mice. Puerarin could significantly inhibit inflammatory reaction caused by DChsp and improve endothelium dilation.

CONCLUSIONHsp60 could activate DCs in vitro and in vivo, Puerarin could significantly inhibit specific immunity induced by HSP60 and improve vascular endothelium-dependent dilation.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Apolipoproteins E ; genetics ; B7-2 Antigen ; immunology ; Cell Proliferation ; drug effects ; Chaperonin 60 ; metabolism ; Dendritic Cells ; drug effects ; enzymology ; immunology ; Endothelium, Vascular ; drug effects ; physiology ; Immunity ; drug effects ; Inflammation ; chemically induced ; Isoflavones ; pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protective Agents ; pharmacology ; T-Lymphocytes ; drug effects ; Vasodilator Agents ; pharmacology