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Objective To investigate the value of serum levels of peroxisome proliferater-activated receptor (PPAR)γin patients with rheumatoid arthritis (RA) and to explore the associations between serum PPARγwith disease activity of RA and RA-associated osteoporosis (OP).Methods One hundred and one cases of hospitalized patients with RA were enrolled.A total of 88 normal subjects during the same period were recruited as the control group.Levels of serum PPARγwere detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absortiometry.All the clinical and laboratory indexes of RA patients were recorded in detail.T-test (or t'-test) was used for comparison of measurement data between the two groups,non-parametric test was applied for skewed distribution data.Comparison of incidence was analyzed with x2 test,correlation analysis was represented ascorrelation coefficient (r).Results Binary logistic regression analysis was used for multivariate regression analysis.Serum levels of PPARγ(3.38/4.00 ng/ml) in RA patients were higher than thosein normal subjects (2.63/1.76) ng/ml (Z=3.204,P=0.001).The positive rate of serum levels of PPARγin RA was 35.6％ (36/101),while the positive rate in the controls was (2.3％,2/88,x2=32.602,P＜0.01).The incidence of OP in RA was 34.7％(35/101;while the levels of serum PPARγ in RA without OP at femur area (femoral neck,total hip) and lumbar spine (L1,L1-4) were higher than that in RA with OP (P＜0.05).Serum levels of PPARγ between groups with different disease activity had no significant difference (P＞0.05).Serum levels of PPARγ in RA with negative RF or negative anti-CCP were higher than thosetin the RA group with positive RF or positive anti-CCP(P＜0.05).Serum levels of PPARγ in RA were negatively correlated with serum RF,anti-CCP,hemoglobin (P ＜0.05-0.001),and positively correlated with erythrocyte sedimentation rate,platelet,BMD at sites of femur neck andWard (P＜0.05-0.001).Results of binary logistic regression analysis showed that levels of serum PPARγwere protective factors in RA for OP at femurneck [OR=0.577,P=0.005,95％CI (0.394-0.846)],and total hip [OR=0.754,P=0.033,95％CI (0.581-0.978)].Condusion Serum levels of PPARγ in patients with RA are significantly increased,and negatively correlate with autoantibodies.Serum levels of PPARγare protective factors for OP in RA.
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Background Peroxisome proliferator-activated receptor gamma (PPARγ) is one of nuclear transcription factors.It plays potential anti-inflammation,anti-fibrogenesis,anti-angiogenesis and neuroprotection roles in human.So the study of its physiological and pathological function in human and animals is still a focus.To understand the distribution of PPARγ in ocular tissues is important for the target treatment of eye diseases.Objective Current study was to investigate the expression of PPARγ in different parts of eye in rodent.Methods Cornea,lens,ciliary,retina and optical nerve were isolated from 6 SPF C57BL/6J mice and 1 SD rat.Western blot assay was used to detect the expressions of PPARγprotein in cornea,lens and retina.Immunohistochemistry was used to locate the distribution of PPARγ protein in cornea,lens,ciliary,retina and optical nerve.Also,the co-expression of PPARγ with glutamine synthetase (GS) (a Müller cell specific marker) and glial fibrillary acidic protein (GFAP)(an astrocyte specific marker) in retina and optic nerve was detected by immunofluorescent double staining.Results Western blot assay showed that PPARγ was expressed in the cornea,lens and retina of the mice.Immunohistochemistry revealed that PPARγ mainly located at corneal epithelium with the strongest staining in the basal cells,but only weak staining was seen in corneal endothelial cells and stroma cells.PPARγ was strongly expressed in epithelial cells and shallow cortex layer of mouse lens.In mouse retina,PPARγ was extensively and richly expressed in retinal ganglion cell layer,inner and outer plexiform layers and inner nuclear layer.In addition,PPARγ was also expressed in the non-pigmented epithelial cells in ciliary body.The co-locations of PPARγexpression with GS in retinal tissue and PPARγ expression with GFAP in optical nerve tissue were found in the mice.Conclusions PPARγis proved to distribute extensively in different ocular tissues.These results offer basis for the target treatment of relevant eye diseases.
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Objective To investigate the effects and mechanisms of rosiglitazone on the expressions of nuclear factor-κB and matrix metalloprotease (MMP-9) in peripheral blood monocyte-derived macrophages (MDMs) in patients with coronary heart disease. Method This was a clinical case-control study. Forty-eight actue coronary symdrome (ACS) patients (ACS group), and 20 patients with stable angina (SA) (control group) were collected. They were performed coronary arteriography in the Department of Cardiology of the Second Xiangya Hospital from March to April in 2007. Exclusion criteria included acute infection, trauma or surgery patients within four weeks, cerebral vascular accident, liver and kidney dysfunction, cancer, and so on. The peripheral blood mononuclear cells were isolated and transformed into MDMs with macrophage colony-stimulating factor treatment. The transformed MDMs were randomly assigned into subgrougs and incubated with 0 /μmol/L, 1 μmol/L, 10 μmol/L, 20 μmol/L of rosiglitazone respectively. The expressions of PPAR-γ mRNA, MMP-9 mRNA were determined by RT-PCR and nuclear factor-κB P65 (NF-KB P65) expression by immunohistochemistry. Multiple comparisons were examined for significant differences using analysis of variance (ANOVA). Results The basal expression of PPAR-y mRNA was lower, in contrast, the levels of NF-KB P65 and MMP-9 mRNA were higher in ACS group than control group. PPAR-γ mRNA expression were significantly upregulated in both ACS and control groups with rosiglitazone treatment. PPAR-γ mRNA expression was positive correlation, while the expressions of MMP-9 mRNA were negative correlation with the rosiglitazone concentration in the ACS group. Rosiglitazone inhibited the expression of NF-KB in a concentration-independent manner in ACS and control groups. Conclusions The expression of PPAR-y mRNA is inhibited, while the activity of NF-KB and expression of MMP-9 mRNA are enhanced in MDMs of ACS cases. Rosiglitazone intervention may inhibit NF-KB activity and MMP-9 expression by upregulation of PPAR-y expression in MDMS of patiens with ACS.
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Objective To investigate the effects of 15-deoxy-?12,14-prostaglandin J2(15d-PGJ2) and DDP on the growth of human pulmonary carcinoma PLA-801D cells and the mechanisms of apoptosis.Methods The human pulmonary carcinoma PLA-801D cells were selected and added to each well of 96-well place and cultivated for 24 h.Then the cells were treated with different concentrations of 15d-PGJ2(0,5,10,20,40 and 80 ?g?L-1) or 15d-PGJ2 combined with DDP(3 mg?L) for 24 h.0 ?g?L-1 15d-PGJ2 group was control group.The morphological changes of cells were observed under inverted microscope.Microculture tetrazolium(MTT)dye was applied to detect the proliferation of the human pulmonary carcinoma PLA-801D cells treated with 15d-PGJ2 and DDP.Diphenylamine assay(DPA) was used to evaluate the activation.Flow cytometry assay(FCM) was used to detect the apoptosis proportion and the changes of cell cycle.Results When the human pulmonary carcinoma PLA-801D cells were treated with low-concentration 15d-PGJ2 alone(5,10 and 20 ?g?L-1),no significant difference was observed in the inhibitory rate of cell growth and the apoptotic indexes such as the apoptosis proportion,the percent of DNA fragmentation and the activity of caspase-3 compared with control group(P
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Objective To study the inhibitive effect and mechanism of PPAR?1 on the extracellular matrix (ECM) accumulation of mesangial cells induced by Ang Ⅱ .Methods The plasmid of PPAR?1/WT (wild type) was transfected into mesangial cells. After 48 hours of Ang Ⅱ stimulation, the gene expression of TGF-?1, PAI-1, c-fos and c-jun was examined by RT-PCR. Protein levels of p-ERK, I-?B and nucleus/cytosol ratio of NF-?B were estimated by Westen-blot. The concentrations of FN and TGF-?1 were estimated by ELISA. The activity of PPAR?1 was examined by specific PPRE binding activity. Plasmid expressing non-functional dominant negative type of mPPAR?1, pIRES2-EGFP-mPPAR?1/DN (DN), and blank plasmid, pIRES2-EGFP (Blank) were used as controls. Effects of 6 ?mol/L PPAR? agonist pioglitazone (Pio) were also studied. Results The expression of TGF-?1 and PAI-1 mRNA in mesangial cells induced by Ang Ⅱ was inhibited by PPAR?1(P