Objective To explore the regulation of peroxisome proliferator-activated receptor γ coactivator 1α( PGC-1α) and NF-E2-related factor 2( Nrf2) on expression of γ-glutamylcysteine synthetase ( γ-GCS) , and their roles in chronic obstructive pulmonary disease( COPD) . Methods Twenty-four SD rats were randomly divided into a COPD group and a normal control group. COPD model was established by intratracheal instillation of lipopolysaccharide ( LPS) and daily exposure to cigarette smog in the COPD group. The lung function was measured and the pathological changes were observed. The protein and mRNA expressions of PGC-1α, Nrf2, and γ-GCS in lung tissue were measured by immunohistochemistry, Western blot, in site hybridization ( ISH) , and reverse transcription-polymerase chain reaction ( RT-PCR ) ,respectively. Results In the COPD group, the pulmonary function ( FEV0. 3, FEV0. 3 /FVC, PEF) damage and lung pathological changes were conformed as morphological characteristics of COPD. The mRNA of PGC-1α and Nrf2 expressed in lung tissues of two group rats in the region consistent with γ-GCS mRNA. The protein and mRNA expressions of PGC-1αand γ-GCS were markedly increased in the COPD group( all P lt;0. 05) ,and the protein expression of Nrf2 was obviously up-regulated ( P lt; 0. 01) , while Nrf2 mRNA had no significant difference between the two groups( P gt;0. 05 ) . Linear correlation analysis showed that the level ofPGC-1αprotein was positively correlated with the levels of Nrf2 protein and mRNA ( r = 0. 775, 0. 515, all P lt; 0. 01) , and the levels of PGC-1αand Nrf2 protein were positively correlated with the levels of γ-GCS protein ( r = 0. 531, 0. 575, all P lt; 0. 01) and mRNA ( r = 0. 616, 0. 634, all P lt; 0. 01) . Conclusions PGC-1α, which may serve as a co-activator of Nrf2, can up-regulate the expression of γ-GCS gene cooperatively with Nrf2 through a common pathway, which might involve in the oxidative and antioxidative mechanism in the pathogenesis of COPD.
ObjectiveTo summarize the research advancement of peroxisome proliferator-activated receptor γ (PPARγ) agonists inhibiting transforming growth factor-β (TGF-β)-induced organ fibrosis. MethodsThe related literatures on PPARγ agonists inhibiting TGF-β-induced organ fibrosis were reviewed. ResultsTGF-β was a major fibrosispromoting cytokine, which could promote a variety of organ fibrosis. PPARγ agonists could effectively block TGFβ signal transduction, and then suppressed organ fibrosis well. ConclusionsThe main antifibrotic mechanism of PPARγ agonists is to inhibit TGF-β signal transduction. The studies on this mechanism will help promoting the clinical application of PPARγ agonists, and provide a new way of the treatment for organ fibrosis.
【Abstract】Objective To study the regulatory ability of peroxisome proliferatoractivated receptor γ(PPARγ) ligands to the inflammatory response in human gallbladder epithelial cells. Methods Culture human gallbladder epithelial cells and identify them . Cells were treated for 24 hours with 0, 10 μmol/L, 20 μmol/L, 30 μmol/L, 50 μmol/L and 100 μmol/L of Ciglitazone during cellular growth peak(5th day), then stimulated them with hIL-1β 5 ng/ml for 2 hours and measured the concentration of IL-6、IL-8 and TNF-α in cellular supernatants by riadioimmunoassay. Results Contrasted with control group, the expression of IL-6 and IL-8 in each test group were inhibited （P＜0.001）. The IL-6 and IL-8 levels were gradually dropped and corelated with the dosage of Cigtitazone, and manifested dosagedependence (P＜0.001). The concentration of TNF-α could not be measured. Conclusion PPARγ ligands can inhibit the expression of IL-6 and IL-8 in human gallbladder epithelial cells and probably produce effect in the regulation of cholecystic inflammation.
ObjectiveTo investigate the effect of pharmacologic delay with pioglitazone, a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, on extended perforator flap survival in a rat model. MethodsSeventy male Sprague Dawley rats, weighing 250-300 g, were randomly divided into control group (n=35) and experimental group (n=35). A three-territory flap was made, including two choke zones. Pioglitazone was dissolved in 1.5 mL saline. Oral doses of pioglitazone[10 mg/(kg·d)] was given by gavaged for 5 days in the experimental group, while the same volume of saline was given in the control group at same time point. After 7 days, the flap survival area was measured and angiographic diagnosis was made. The tissue samples were harvested from choke zone Ⅱ for histological study and vascular endothelial growth factor (VEGF) expression detection by immunohistochemical staining. The content of nitric oxide (NO) in choke zones I and Ⅱ was measured at immediate, 1, 3, 5, and 7 days after operation. ResultsThe flap general change of 2 groups was similar. Varying degrees of necrosis occurred with the extension of time in 2 groups. At 7 days after operation, the flap survival rate was 87.73%±3.25% in the experimental group and 76.07%±2.92% in the control group, showing a significant difference (t=-10.338, P=0.000). The number of true anastomosis in choke zones I and Ⅱ was 5.40±1.14 and 3.00±0.71 in the experimental group, and was 3.20±0.84 and 0.80±0.84 in the control group respectively, showing significant differences between the 2 groups (t=-3.479, P=0.008;t=-4.491, P=0.002). The microvessel density and the expression of VEGF in choke zone Ⅱ of experimental group were (33.16±7.73)/mm2 and 4 368.80±458.23, respectively, which were significantly higher than those of control group[(23.29±5.91)/mm2 and 2 241.24±554.43] (t=5.073, P=0.000;t=-14.789, P=0.000). The content of NO in the experimental group were significantly higher than those in the control group at other time points (P<0.05) except for at immediate after operation. ConclusionPharmacologic delay with pioglitazone can improve extended perforator flap viability through increasing ischemia-induced angiogenesis and choke vessels vasodilation in rat models.