Peroxisome proliferator-activated receptor gamma (PPARγ) activation: a potential treatment for ascites syndrome in broiler chickens.

Ascites (serous fluid accumulation in the abdominal cavity) has been observed worldwide in fast growing broilers. Pulmonary vascular remodeling is an important pathological feature of broiler ascites syndrome. Peroxisome proliferators-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) are expressed in pulmonary vascular endothelial cells and vascular smooth muscle cells (VSMC) where they participate in the regulation of normal pulmonary vascular function. The objective of the present study was to investigate the effects of omega-3 fatty acids (found in fish oil) and pioglitazone (PIO) as natural and synthetic PPARγ ligands supplementation on PPARγ and PGC-1α expression in the prevention of pulmonary arterial hypertension (PAH) syndrome in broiler chickens. The experiment was conducted with 4 treatment groups: 1) negative control, normal temperature conditions with basal diet; 2) positive control, low-temperature conditions with basal diet; 3) positive control + 10 mg PIO/kg of weight/d and 4) positive control + 1% FO. Each treatment had 5 replicates. Ascites heart index (RV/TV) was significantly (P < 0.05) reduced in chickens receiving FO (0.20) and PIO (0.21) compared to the positive control group (0.26). The addition of PIO in broilers under cold-induced ascites significantly increased the expression of PPARγ (9.44) and PGC-1α (5.81) genes in lung tissue compared to the negative control group (1.03, P < 0.05). Proliferative indexes of VSMC in pulmonary arteries such as PMT, PIT, and percentage wall thickness were significantly elevated in positive control group, indicating that pulmonary vascular remodeling occurred following VSMC proliferation in ascites. The vessel internal diameter was increased in FO and PIO groups. Based on these results, activation and expression of PPARγ and PGC-1α genes as a critical regulator of pulmonary artery smooth muscle cell using ligands, especially PIO, can be effective in reducing the incidence of PAH in broiler chickens.

Pyridine pigments from functional Monascus rice / 药学学报

The trace chemical components in functional Monascus rice were studied to explore the potential bioactive substances. MCI column, Sephadex LH-20 gel, and preparative liquid chromatography were used to purified the ethyl acetate extract from functional Monascus rice. Two novel pyridine Monascus pigments were isolated and identified, named monascopyridine G (1) and monascopyridine H (2), respectively based on extensive mass spectrometry (MS), infrared radiation (IR), and nuclear magnetic resonance (NMR) analysis. The molecular docking experiments between compounds 1 and 2 and peroxisome proliferators-activated receptor-gamma (PPARγ) showed that they exhibited obvious binding force with the receptor protein. Besides, the biosynthetic pathways of the two compounds were proposed, which provide a valuable reference for the selective production of these potential bioactive substances.

Effects of sodium arsenite on mitochondrial function and expression of SIRT1/PGC-1α pathway-related proteins in human normal liver cell / 环境与职业医学

Background Long-term exposure to arsenic can cause liver injury of varying degrees. Mitochondrial damage may be an early key event of arsenic-induced liver injury. Silent mating type information regulation 2 homolog 1 (SIRT1)/ recombinant peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important pathway regulating mitochondrial mass and function. However, whether arsenic-induced liver injury is related to mitochondrial dysfunction mediated by SIRT1/PGC-1α pathway remains unclear. Objective To investigate potential effects of sodium arsenite (NaAsO2) on mitochondrial function and expressions of SIRT1/PGC-1α pathway-related proteins in human normal liver cell. Methods Human normal liver cells (MIHA cells) were used as the research object. MIHA cells were treated with different concentrations of NaAsO2 (0, 5, 10 and 20 μmol·L−1) for 24 h, and the cells were collected for study. The ultrastructure of mitochondria was observed by transmission electron microscopy, adenosine triphosphate (ATP) concentration by fluorescence method, mitochondrial membrane potential (MMP) level by flow cytometry, and SIRT1, PGC-1α and their downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) protein expression levels by Western blotting. One-way analysis of variance and trend test were used for data statistical analysis. Results The viability of MIHA cells decreased gradually with the increase of NaAsO2 concentration (F=6495.47, P<0.001). The transmission electron microscope observation showed that the size of mitochondria in the 10 μmol·L−1 NaAsO2 treatment group was different, and the mitochondria were swollen or elongated in a rod-like shape. The mitochondria in the 20 μmol·L−1 NaAsO2 treatment group swelled like air spheres or vacuoles. The ATP concentration and MMP level of MIHA cells gradually decreased with the increase of NaAsO2 concentration (Ftrend of ATP=172.28, Ftrend of MMP=59.91, both Ps<0.001). Compared with the control group, the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were not significantly changed in the 5 μmol·L−1 NaAsO2 treatment group, while the protein expression levels of SIRT1, PGC-1α, and TFAM were decreased in the 10 μmol·L−1 NaAsO2 treatment group, and the protein expression levels of SIRT1, PGC-1α, and NRF1 were decreased in the 20 μmol·L−1 NaAsO2 treatment group. The results of trend test showed that the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM decreased gradually with the increase of NaAsO2 concentration (Ftrend of SIRT1=47.07, P<0.001; Ftrend of PGC-1α=15.17, P<0.01; Ftrend of NRF1=13.54, P<0.01; F trend of TFAM=4.20, P<0.05). Conclusion The down-regulation of SIRT1/PGC-1α and its downstream NRF1 and TFAM may be involved in NaAsO2-induced mitochondrial dysfunction in liver cells.

Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling.

BACKGROUND: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown. MATERIALS AND METHODS: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses. RESULTS: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1ß and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect. CONCLUSION: This study revealed the joint protective  advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.

Peroxisome proliferators-activated receptor gamma polymorphisms and colorectal cancer risk.

AIMS: Several studies evaluated the association between peroxisome proliferators-activated receptor gamma (PPARγ) Pro12Ala (rs1801282), and His477His (rs3856806) polymorphisms and the risk of colorectal cancer (CRC). However, the results were not stable. MATERIALS AND METHODS: We searched databases containing PubMed and EMBASE. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: A significantly decreased CRC risk was found for PPARγ Pro12Ala polymorphism (OR = 0.88, 95% CI 0.83-0.94, P < 0.0001). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.89, 95% CI 0.83-0.95, P = 0.0003) but not in Asian population (OR = 0.76, 95% CI 0.57-1.02, P = 0.07). In the subgroup analysis by CRC location, significantly decreased risks were found in rectal cancer (OR = 0.88, 95% CI 0.77-1.00, P = 0.05) and colon cancer (OR = 0.82, 95% CI 0.73-0.92, P = 0.0008). In addition, a significantly decreased CRC risk was also detected for PPARγ His477His polymorphism (OR = 0.66, 95% CI 0.44-1.00, P = 0.05). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.43, 95% CI 0.26-0.69, P = 0.0006) but not in Asian population (OR = 0.95, 95% CI 0.73-1.25, P = 0.72). CONCLUSIONS: PPARγ Pro12Ala and His477His polymorphisms might be associated with susceptibility of CRC.

14,15-epoxyeicosatrienoic acid promotes production of brain derived neurotrophic factor from astrocytes and exerts neuroprotective effects during ischaemic injury.

AIMS: 14,15-Epoxyeicosatrienoic acid (14,15-EET) is abundantly expressed in brain and exerts protective effects against ischaemia. 14,15-EET is hydrolysed by soluble epoxide hydrolase (sEH). sEH-/- mice show a higher level of 14,15-EET in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic conditions. However, it is unclear whether the neuroprotective effect of 14,15-EET is associated with astrocytes. METHODS: A mouse model of focal cerebral ischaemia was induced by middle cerebral artery occlusion. Oxygen-glucose deprivation/reoxygenation (OGD/R) was performed on cultured murine astrocytes, neurons and a human cell line. Cell viabilities were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The mRNA expressions were quantified by real-time PCR. Brain derived neurotrophic factor (BDNF) concentration was measured by ELISA. Protein expressions were quantified by Western blotting. BDNF and peroxisome proliferators-activated receptor gamma (PPAR-γ) expressions were analysed by confocal microscopy. RESULTS: Decreased infarct volumes, elevated BDNF expression and increased numbers of BDNF/GFAP Glial Fibrillary Acidic Protein double-positive cells were observed in the ischaemic penumbra of sEH-/- mice. The decreased infarct volumes of sEH-/- mice were diminished by intracerebroventricular injection of a blocker of BDNF receptor. 14,15-EET increases BDNF expression and cell viability of murine astrocytes and U251 cells by BDNF-TrkB Tyrosine receptor kinase-B-extracellular signal-regulated kinase 1/2 signalling during OGD/R. 14,15-EET protects neurons from OGD/R by stimulating the production of astrocyte-derived BDNF. 14,15-EET stimulates the production of astrocyte-derived BDNF through PPAR-γ/p-cAMP-response element binding protein signal pathways. CONCLUSIONS: Our study demonstrates the importance of 14,15-EET-mediated production of astrocyte-derived BDNF for enhancing viability of astrocytes and protecting neurons from the ischaemic injury and provides insights into the mechanism by which 14,15-EET is involved in neuroprotection.

Pioglitazone modulates the proliferation and apoptosis of vascular smooth muscle cells via peroxisome proliferators-activated receptor-gamma.

BACKGROUND: PPARγ is a member of the nuclear hormone receptor superfamily. It has been considered as a mediator regulating metabolism, anti-inflammation, and pro-proliferation in the Vascular Smooth Muscle Cells (VSMCs). Thiazolidinediones (TZDs), synthetic ligands of PPARγ, have anti-proliferative and pro-apoptotic effects on VSMCs, which prevent the formation and progression of atherosclerosis and restenosis following percutaneous coronary intervention (PCI). However, the underlying mechanism remains elusive. This present study therefore aimed to investigate the signaling pathway by which pioglitazone, one of TZDs, inhibits proliferation and induces apoptosis of VSMCs. METHODS: The effects of pioglitazone on VSMC proliferation and apoptosis were studied. Cell proliferation was determined using BrdU incorporation assay. Cell apoptosis was monitored with Hoechst and Annexin V staining. The expression of caspases and cyclins was determined using real-time PCR and Western blot. RESULTS: Pioglitazone treatment and PPARγ overexpression inhibited proliferation and induced apoptosis of VSMCs, whereas blocking by antagonist or silencing by siRNA of PPARγ significantly attenuated pioglitazone's effect. Furthermore, pioglitazone treatment or PPARγ overexpression increased caspase 3 and caspase 9 expression, and decreased the expression of cyclin B1 and cyclin D1 in VSMCs. CONCLUSIONS: Pioglitazone inhibits VSMCs proliferation and promotes apoptosis of VSMCs through a PPARγ signaling pathway. Up-regulation of caspase 3 and down-regulation of cyclins mediates pioglitazone's anti-proliferative and pro-apoptotic effects. Our results imply that pioglitazone prevents the VSMCs proliferation via modulation of caspase and cyclin signaling pathways in a PPARγ-dependent manner.

Analysis of aquaporin 9 expression in human epidermis and cultured keratinocytes.

Aquaporin 9 (AQP9) is a member of the aquaglyceroporin family that transports glycerol, urea and other small solutes as well as water. Compared to the expression and function in epidermal keratinocytes of AQP3, another aquaglyceroporin, our knowledge of epidermal AQP9 remains elusive. In this study, we investigated the expression of AQP9 in the human epidermis and cultured keratinocytes. Immunofluorescence studies revealed that AQP9 expression is highly restricted to the stratum granulosum of the human epidermis, where occludin is also expressed at the tight junctions. Interestingly, the AQP3 staining decreased sharply below the cell layers in which AQP9 is expressed. In cultured normal human epidermal keratinocytes (NHEK), knock-down of AQP9 expression in the differentiated cells induced by RNA interference reduced glycerol uptake, which was not as pronounced as was the case with AQP3 knock-down cells. In contrast, similar reduction of urea uptake was detected in AQP9 and AQP3 knock-down cells. These findings suggested that AQP9 expression in NHEK facilitates at least the transport of glycerol and urea. Finally, we analyzed the effect of retinoic acid (RA), a potent stimulator of keratinocyte proliferation, on AQP3 and AQP9 mRNA expression in differentiated NHEK. Stimulation with RA at 1 µM for 24 h augmented AQP3 expression and down-regulated AQP9 expression. Collectively, these results indicate that AQP9 expression in epidermal keratinocytes is regulated in a different manner from that of AQP3.

Dietary fish oil reduces systemic inflammation and ameliorates sepsis-induced liver injury by up-regulating the peroxisome proliferator-activated receptor gamma-mediated pathway in septic mice.

This study investigated the effect of dietary fish oil on systemic inflammation and hepatic injury in mice with polymicrobial sepsis. Male ICR mice were assigned to a control group (C, n=30) and a fish oil group (FO, n=30). Mice in the C group were fed a semi-purified diet with 10% soybean oil, and those in the FO group were fed a fish oil diet (2.5% fish oil+7.5% soybean oil; w/w). Three weeks later, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed at 0, 6 and 24 h after CLP, respectively. Results showed that compared with C group, the FO group had lower plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nitrite at 6 and 24 h after CLP. Also, peritoneal lavage fluid concentrations of TNF-α and prostaglandin (PG) E2 were significantly lower at 24 h in the FO than in the C group. The FO group had lower myeloperoxidase activities at 6 h after CLP in various organs. Plasma aminotransferase and alanine aminotransferase activities revealed significantly decreased in the FO group. The DNA-binding activity of peroxisome proliferators-activated receptor gamma (PPARγ) and mRNA expression of I kappaB alpha (IκBα) were up-regulated while nuclear factor (NF)-κB p65 DNA-binding activity, inducible nitric oxide synthase protein expression and the concentration of nitrotyrosine were significantly decreased in the FO group in liver after CLP. These results indicate that dietary fish oil administration may attenuate systemic inflammation and up-regulate hepatic PPARγ DNA-binding activity, which may consequently have ameliorated liver injury in these septic mice.

Polimorfismo Pro12Ala del gen PPAR-γ 2 y síndrome metabólico: Estudio preliminar / Pro12Ala polymorphism of the PPAR-gamma2 gene and the metabolic syndrome: Preliminary study

El objetivo de este estudio fue determinar la prevalencia del polimorfismo Pro12Ala del gen PPARgamma2 en individuos no emparentados con síndrome metabólico de la ciudad de Maracaibo. Se seleccionaron 50 individuos (22 con síndrome metabólico y 28 sin síndrome metabólico) entre 22 y 58 años. A cada individuo se le realizó una evaluación clínica, nutricional y bioquímica. Para analizar la secuencia de la variante Pro12Ala del gen PPAR se empleó PCR y digestión enzimática de los fragmentos de restricción del polimorfismo (PCR-RFLP). En los individuos con síndrome metabólico el porcentaje de portadores del alelo Ala fue de 13,6%, mientras que en el grupo sin síndrome metabólico fue de 32,14%. La frecuencia para el alelo Ala del polimorfismo Pro12Ala fue de 0,12 y para el alelo Pro fue de 0,88. Los individuos con síndrome metabólico y portadores del alelo Ala presentaron niveles más bajos de triglicéridos y col-HDL más alto. Se concluye que la presencia del alelo Ala en individuos con síndrome metabólico mostró un efecto protector sobre el perfil lipídico.

The aim of this paper was to determine the prevalence of the polymorphism pro12ala in non-related individuals with metabolic syndrome from Maracaibo-Venezuela. Fifty subjects (22 with metabolic syndrome and 28 without metabolic syndrome) between 22 to 58 years of age were selected. For each individual, biochemical, nutritious, and clinical evaluations were carried out. PCR and restriction-fragment length polymorphism enzyme digestion were used to analyze the Pro12Ala sequence variant of the PPAR gene. The distribution of the Ala allele was 13.6% in the individuals with metabolic syndro- and 32.14% in the group without metabolic syndrome. The frequency distributions of the PPAR gamma sequence variants were 0.12 for Ala variant and 0.88 for Pro. The subjects with the metabolic syndrome and carriers of the Ala 12 allele had lower concentration of triglycerides and higher HDL-C. It can be concluded that the Ala12 allele in individuals with metabolic syndrome had a protective effect on the lipid profile.

The protective effect of sodium hyaluronate on the cartilage of rabbit osteoarthritis by inhibiting peroxisome proliferator-activated receptor-gamma messenger RNA expression.

PURPOSE: The purpose of this study was to study the protective effect and influence of sodium hyaluronate (Na-HA) on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-gamma) in cartilage of rabbit osteoarthritis (OA) model. MATERIALS AND METHODS: Forty eight white rabbits were randomly divided into A, B, and C groups. Group A was normal control group, B and C groups underwent unilateral anterior cruciate ligament transection (ACLT). The rabbits in group B were injected normal saline after ACLT; and Group C received intra-articular 1% sodium hyaluronate (HA) injection 5 weeks after surgery, 0.3 mL once a week. At 11th week after surgery, all the rabbits were sacrificed. The cartilage changes on the medial femoral condyles were graded separately. Cartilage sections were stained with safranin-O and HE, and messenger RNA (mRNA) expression of PPAR-gamma was detected by using real time polymerase chain reaction (Real Time-PCR). RESULTS: Cartilage degeneration in group B was significantly more severe than in A and C injection group. The grey value of Safranin-O of B group was higher than A and C groups. Expression of PPAR-gamma mRNA in group B was higher than group A and C. CONCLUSION: This study shows that Na-HA has a protective effect on articular cartilage degeneration, and the inhibitory effect on the PPAR-gamma mRNA expression may be one of therapeutic mechanism of Na-HA.

The protective effect of sodium hyaluronate on the cartilage of rabbit osteoarthritis and its effects on PPAR-gamma mRNA expression / 中华风湿病学杂志

Objective To observe the protective effect of sodium hyaluronate (Na-HA),and its effects on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-γ) in cartilage of rabbit osteoarthritis (OA) model.Methods Forty eight white rabbits were divided into A,B,C groups randomly.Group A were normal controls,groups B and C were underwent unilateral anterior cruciate ligament transection (ACLT).The rabbits in group B were injected normal saline after ACLT;Group C rabbits received intra-articular 1% sodium hyaluronate (HA) injections 5 weeks after surgery,0.3 ml once a week.At week 11 after the surgery,all rabbits were sacrificed.The cartilage changes on the medial femoral condyles were graded.Cartilage sections were stained with safranin-O and HE,mRNA expression of PPAR-γ was detected by real time polymerase chain reaction (Real Time-PCR).Results Cartilage degeneration in group B was significantly more severe than in groups A and C.The grey value of Safranin-O of B group were higher than groups A and C.Expression of PPAR-γ mRNA in group B was higher than that in groups A and C.Conclusion NaHA has a protective effect on articular cartilage degeneration,and the inhibitory effect on PPAR-γ mRNA expression may be one of the therapeutic mechanism of Na-HA.

The Protective Effect of Sodium Hyaluronate on the Cartilage of Rabbit Osteoarthritis by Inhibiting Peroxisome Proliferator-Activated Receptor-Gamma Messenger RNA Expression

PURPOSE: The purpose of this study was to study the protective effect and influence of sodium hyaluronate (Na-HA) on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-gamma) in cartilage of rabbit osteoarthritis (OA) model. MATERIALS AND METHODS: Forty eight white rabbits were randomly divided into A, B, and C groups. Group A was normal control group, B and C groups underwent unilateral anterior cruciate ligament transection (ACLT). The rabbits in group B were injected normal saline after ACLT; and Group C received intraarticular1% sodium hyaluronate (HA) injection 5 weeks after surgery, 0.3 mL once a week. At 11th week after surgery, all the rabbits were sacrificed. The cartilage changes on the medial femoral condyles were graded separately. Cartilage sections were stained with safranin-O and HE, and messenger RNA (mRNA) expression of PPAR-gamma was detected by using real time polymerase chain reaction (Real Time-PCR). RESULTS: Cartilage degeneration in group B was significantly more severe than in A and C injection group. The grey value of Safranin-O of B group was higher than A and C groups. Expression of PPAR-gamma mRNA in group B was higher than group A and C. CONCLUSION: This study shows that Na-HA has a protective effect on articular cartilage degeneration, and the inhibitory effect on the PPAR-gamma mRNA expression may be one of therapeutic mechanism of Na-HA.

Effect of angiotensin receptor blocker on the expressions of NF-κB PPARγ in adipose tissue of high-fat- diet induced insulin resistant rats / 中华内分泌代谢杂志

The expressions of NF-κB and PPARγ were increased in adipose tissue of insulin resistant rats.The angiotensin receptor blocker decreased NF-κB protein expression by 21%,increased PPARγ protein expression by 28%and diminished adipocyte size,suggesting that these findings may be involved in the improvement of obesity-induced inflammation and insulin resisitance.

Effects of peroxisome proliferators activated receptor-ganmma(PPAR-γ)on ischemia-reperfusion injury of bilr ducts after orthotopic liver transplantationwith / 中华急诊医学杂志

Objective To explore the effects and mechanism of peroxisome proliferators activated receptor-gamma(PPAR-γ)and its ligand rosiglitazone on ischemia-reperfusion injury of the donor bile ducts.Method Forty-two SD rats were randomly divided into three groups with fourteen rats in each:the sham operation group (SO),ischemia-reperfusion(I/R)group and I/R+rosiglitazone group(I/R+Ros).The animal model of is-chemia-reperfusion occurred in the orthotopically transplanted liver was used.Tne signal pathway of iuflanunatory response of bile duets of the transplanted hver and the variations of associated cytokines were detected by the signal transduction pathway-finder gene array and cytokine antibody chips.The pathological changes and the biochemical markers of the donor liver were assessed by histopathological score and the estimation of the functional changes of some other organs.Data were analyzed by using SPSS version 10.0 software package.Statistical analysis was car-ried out by using one-way anova and Bonferroni test.Results Compared with the SO group and I/R+Ros group.the expression of NF-кB gene of I/R group to more than two times,and the levels of IL-1α,IL-1β and TNF-α pro-tein expressions in I/R group went up over double too.Compared with I/R group,the histopathological score and the biochemical markers of I/R+Ros group were significantly lower (P＜0.05,P＜0.01,respectively).Con-clusions PPAR-γ and its ligand rosiglitazone have protective effects on ischemia-reperfusion injury to donor bile ducts.The mechanism may be attributed to decrease in the release of inflammatory mediators(IL-1α,IL-1β,TNF-α and so on)resulted from the down-expression of decreased due to NF-кB.

Association between bone mineral density and peroxisome proliferators-activated receptor gamma C161T gene in women of the Han nationality in Beijing area / 中国实用内科杂志

0.05).Conclusion A silent C161 T polymorphism of PPAR? gene might not be genetic markers of osteoporosis,which might not be employed to screen the high risk population of osteoporosis in Chinese women of Han nationality.

Effects of atorvastatin on expressions of peroxisome proliferators-activated receptor gamma and MMP-9 in atherosclerosis rabbits / 吉林大学学报(医学版)

Objective To study the effects of atorvastatin on the expressions of peroxisome proliferators-activated receptor gamma(PPAR?)and matrix metalloproteinase-9(MMP-9)in atherosclerosis(AS) tissue.Methods Atherosclerotic rabbit models on aortas were established with the high-cholesterol diet,and animals were divided into control,model and atorvastatin groups(n=8).The expressions of PPAR? and MMP-9 and the effects of atorvastatin on them were observed by means of immunohistochemistry.Results The expression of PPAR? in model group(14.38%?2.58%)was higher than that in control group(7.82%?0.96%)(P

Effect of PTEN Gene in Regulation of Growth of Hepatocellular Carcinoma Cells by PPAR? / 中国普外基础与临床杂志

Objective To study the effects of peroxisome proliferators-activated receptor (PPAR) ? on the growth of human hepatocellular carcinoma cells and explore the roles of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and phospho-Akt in this process. Methods SMMC-7721 cells were treated with 15-d-PGJ2 or pioglitazone, which were two kinds of PPAR? ligands, at different concentrations. The viability of SMMC-7721 cells was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. PTEN mRNA level was determined by RT-PCR. The protein expressions of PTEN and pAkt were measured by Western blot analysis. Results It was demonstrated through MTT assay that both 15-d-PGJ2 and pioglitazone had an inhibitory effect on the growth of SMMC-7721 cells in a time- and dose- dependent manner. According to flow cytometry detection, more cells were arrested in G0/G1 phase. Increased expression of PTEN mRNA was detected in 15-d-PGJ2 or pioglitazone-treated cells through RT-PCR. Increased expression of PTEN protein and decreased expression of pAkt were confirmed by Western blot analysis. Conclusion The ligands of PPAR? could inhibit SMMC-7721 cells proliferation in a time- and dose- dependent manner. The upregulation of PTEN may be involved in the underlying mechanism.

Role of peroxisome proliferators-activated receptor-gamma in phenotypic transforming of vascular smooth muscle cells in hypertension / 第三军医大学学报

Objective To observe the effect of peroxisome proliferators activated receptor gamma(PPAR-?)on phenotypic transforming of vascular smooth muscle cells(VSMC)in hypertension.Methods Spontaneous hypertension rats(SHR)and WKY rats both aged 4 months were included.SHR rats as well as WKY rats were divided to be fed with normal chow,and chow added with rosiglitazone(10 mg?kg-1?d-1)for 16 weeks.VSMC were isolated from SHR rats and WKY rats and cultured by patch-attaching method,then respectively divided into 3 groups after treated with genetic recombination technology:normal VSMC,PPAR? overexpressed VSMC and PPAR? silenced VSMC.Expressions of OPN and ?-SMA,which respectively represent the undifferentiated and differentiated VSMC,were detected by Western blotting.Cell proliferation was determined by detecting DNA synthesis and cell counting.The changes of arteries were evaluated pathologically.Results Rosiglitazone decreased blood pressure and ameliorated vascular remodeling of aorta in SHR rats.Aorta of SHR showed an upregulation of OPN and downregulation of ?-SMA,which could be inhibited by rosiglitazone.VSMC from SHR rats showed an upregulation of OPN and downregulation of ?-SMA,and increased cell proliferation.These changes were all inhibited by rosiglitazone.In the cells that overexpressed PPAR?,the cell proliferation rate was lower,and the expressions of OPN and ?-SMA were depressed,compared with the corresponding control cells.Conclusion PPAR-? could inhibit the phenotypic transforming of VSMC,and this might be responsible for the amelioration of vascular remodeling in hypertension.