Animals ; Apoptosis ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Cell Line ; Hypoxia ; MicroRNAs/genetics* ; Myocardial Reperfusion Injury/drug therapy* ; Myocytes, Cardiac ; Oxidative Stress ; Rats ; Reperfusion Injury ; Tetrahydronaphthalenes/pharmacology*

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Ligands ; Neoplasms ; pathology ; Retinoid X Receptors ; agonists ; chemistry ; pharmacology ; Retinoids ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Tetrahydronaphthalenes ; chemical synthesis ; chemistry ; pharmacology ; Tretinoin ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo investigate the effect of Am80 on innate immune response of Porphyromonas gingivalis (Pg) W83-induced periodontitis in mice.

METHODSTwenty-five mice were randomly divided into five groups, control group, PgW83-induced periodontitis group (periodontitis), Am80 (10 µg/d) treatment group (low-dose group), Am80 (50 µg/d) treatment group (middle-dose group), Am80 (100 µg/d) treatment group (high-dose group). The distance of alveolar bone resorption in each mouse was observed and measured by a dissecting microscope. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of serum anti-Pg specific IgG. The mRNA expression of interferon-γ (IFN-γ) and interleuking-12 (IL-12) in gingival tissues, draining lymph node and spleen were detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The measurement data were statistically analyzed.

RESULTSThe resorption rate in Am80 group [(121 ± 10)%] and high-dose of Am80 group [(108 ± 8)%] was significantly different with that in periodontitis mice [(133 ± 10)% ] (P < 0.05). The serum levels of anti-Pg specific IgG of the Am80 groups of different doses (0.437 ± 0.083, 0.566 ± 0.012, and 0.386 ± 0.078) were significantly lower than that of the periodontitis group (1.151 ± 0.433) (P < 0.001). Real-time quantitative PCR assay showed that after Am80 treatment, the IL-12 mRNA levels in the gingival tissues, lymph nodes and spleen of mice were reduced to 1.107 ± 0.088, 0.806 ± 0.220, and 0.668 ± 0.756, which were all significantly different with those in periodontitis (P < 0.01). Similarly, the relative expression of IFN-γ mRNA levels in gingival tissue, lymph nodes and spleen of mice were reduced to 8.898 ± 0.427, 16.654 ± 5.995, and 1.482 ± 0.033, which were significantly different with periodontitis (P < 0.001).

CONCLUSIONSAm80 can reduce the extent of inflammation and alleviate alveolar bone resorption by modulating innate immune response.

Alveolar Bone Loss ; pathology ; Animals ; Benzoates ; pharmacology ; Gingiva ; immunology ; Immunity, Innate ; drug effects ; Immunoglobulin G ; blood ; Interferon-gamma ; genetics ; metabolism ; Interleukin-12 ; blood ; Mice ; Periodontitis ; blood ; immunology ; microbiology ; Porphyromonas gingivalis ; immunology ; RNA, Messenger ; analysis ; Random Allocation ; Spleen ; immunology ; Tetrahydronaphthalenes ; pharmacology

OBJECTIVETo explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE(-/-)) mice.

METHODSEight C57BL/6 mice served as control, 46 apoE(-/-) mice were randomized into 4 groups: apoE(-/-) group (n = 10), STZ+apoE(-/-) group (n = 12), STZ+apoE(-/-)+Bex 10 (10 mg×kg⁻¹×d⁻¹)group (n = 12), STZ+ apoE(-/-)+Bex 30 (30 mg×kg⁻¹×d⁻¹) group (n = 12). Diabetic apoE(-/-) animal model was established by intraperitoneal injection of STZ. Blood glucose was determined by glucose oxidase method. Patch area in thoracic aorta was measured by HE staining. Western blotting was used to determine the RXR and gp91(phox) protein level in thoracic aorta. Reactive oxygen species (ROS) level in blood and thoracic aorta homogenates was detected by Fenton and Griess method.

RESULTS(1) Patch areas of thoracic aorta were larger in apoE(-/-) group than in C57BL/6 group [(38.40 ± 8.95)µm² vs. (0.10 ± 0.01) µm², P < 0.01], further increased in STZ+apoE(-/-) group [(94.06 ± 8.04)µm², P < 0.05 vs. apoE(-/-) group] and significantly reduced in STZ+apoE(-/-)+Bex 10 group [(78.72 ± 4.62)µm², P < 0.05 vs. STZ+apoE(-/-) group] and further educed in STZ+apoE(-/-)+Bex 30 group [(46.13 ± 7.56)µm², P < 0.05 vs. STZ+apoE(-/-)+Bex 10 group]. (2) Blood glucose level, TG, TC, LDL-C, thoracic aorta gp91(phox) protein level and ROS level in blood and thoracic aorta homogenates were significantly higher in STZ+apoE(-/-) group than in apoE(-/-) group (all P < 0.05). Blood glucose level and TG, TC, LDL-C levels were similar between STZ+apoE(-/-)+Bex10 and STZ+apoE(-/-) group. Thoracic aorta gp91(phox) protein level and ROS level in blood and thoracic aorta homogenates were lower in STZ+apoE(-/-)+Bex 10 group than in STZ+apoE(-/-) group (P < 0.05). Blood glucose level, TG, TC, LDL-C levels, gp91(phox) expression in thoracic aorta, ROS level in blood and thoracic in STZ+apoE(-/-)+Bex 30 group were lower than in STZ+apoE(-/-) group (all P < 0.05).

CONCLUSIONBexarotene treatment could attenuate arteriosclerosis progression in STZ induced diabetic apoE(-/-) mice, the underlying mechanism might be related to suppressing oxidative stress and decreasing blood glucose level and improving lipids metabolism.

Animals ; Apolipoproteins E ; genetics ; Atherosclerosis ; etiology ; metabolism ; prevention & control ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; metabolism ; Retinoid X Receptors ; agonists ; metabolism ; Tetrahydronaphthalenes ; pharmacology