Association of β3 Adrenergic Receptor and Peroxisome Proliferator-activated Receptor Gamma 2 Polymorphisms With Insulin Sensitivity:A Twin Study

Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats

BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma(PPAR-γ) on rat hepatic fibrosis. METHODS:Hepatic fibrosis in rats was induced by CCl4 for 2 weeks(early fibrosis)and 8 weeks(sustained fibrosis).The rats were randomly divided into four groups:normal control, fibrosis,blank vector,and PPAR-γ.They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene by portal vein injection.The liver of the rats was examined histologically and hydroxyproline was assessed.In vitro primary hepatic stellate cells(HSCs)were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene.The status of HSC proliferation was measured by the MTT assay.The protein levels of PPAR-γ,α-smooth muscle actin(α-SMA)and type I collagen expression were evaluated by the Western blotting method. RESULTS:In vitro studies revealed that expression of PPAR-γ inhibited expression ofα-SMA and type I collagen in activated HSCs(P<0.01)as well as HSC proliferation(P<0.01).In vivo experiments indicated that in the early hepatic fibrosis group,the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-γtransfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group;whereas the expressions of PPAR-γ andα-SMA were different compared to the hepatic fibrosis group(P<0.01).In the sustained hepatic fibrosis group,there were significant differences in the hydroxyproline content and the expression of PPAR-γ,α-SMA,and type I collagen between each group.CONCLUSION:PPAR-γcan inhibit HSC proliferation and hepatic fibrosis,and suppressα-SMA and type I collagen expression.

Effect of ligand of peroxisome proliferator-activated receptor γ on the biological characters of hepatic stellate cells

AIM: To study the effect of rosiglitazone, which is a ligand of peroxisome proliferator-activated receptor gamma (PPARγ), on the expression of PPARγ in hepatic stellate cells (HSCs) and on the biological characteristics of HSCs.METHODS: The activated HSCs were divided into three groups: control group, 3 μmol/L rosiglitazone group, and 10 μmol/L rosiglitazone group. The expression of PPARγ,α-smooth muscle actin (α-SMA), and type Ⅰ and Ⅲ collagen was detected by RT-PCR, Western blot and immunocytochemical staining, respectively. Cell proliferation was determined with methylthiazolyltetrazolium (MTT) colorimetric assay. Cell apoptosis was demonstrated with flow cytometry.RESULTS: The expression of PPARγ at mRNA and protein level markedly increased in HSCs of 10 μmol/L rosiglitazone group (tvalue was 10.870 and 4.627 respectively, P<0.01in both). The proliferation of HSCs in 10 μmol/L rosiglitazone group decreased significantly (t = 5.542, P<0.01), α-SMA expression level and type Ⅰ collagen synthesis ability were also reduced vs controls (tvalue= 10.256 and 14.627respectively, P<0.01 in both). The apoptotic rate of HSCs significantly increased in 10 μmol/L rosiglitazone group vs control (x2= 16.682, P<0.01).CONCLUSION: By increasing expression of PPARγ in activated HSCs, rosiglitazone, an agonist of PPARγ,decreases α-SMA expression and type Ⅰ collagen synthesis,inhibits cell proliferation, and induces cell apoptosis.

Protective effect of ghrelin on left ventricular remodeling in spontaneously hypertensive rats is associated with the peroxisome proliferator-activated receptor gamma-dependent pathway

Background Studies suggested that exogenous ghrelin administration could prevent early left ventricular remodeling in rats with myocardial infarction. We investigated herein whether ghrelin attenuated left ventricular remodeling induced by hypertension and whether ghrelin＇s effect was mediated through the peroxisome proliferator-activated receptor gamma （PPAR-y）-dependent pathway. Methods Spontaneously hypertensive rats （8-week-old males） were randomly divided into three groups with 12 rats in each： ghrelin group （received ghrelin 100 IJg/kg subcutaneously （sc） twice daily）; ghrelin＋GW9662 group （received the PPAR-y antagonist GW9662 at 2 mg/kg sc, and then ghrelin as above）; saline controls. Normal male Wistar Kyoto rats （n=-12） served as normal controls. Four weeks later, the effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, and histopathological examination, and gene expression analysis （PPAR-y protein and mRNA expression）. The serum levels of C-reactive protein （CRP） and tumor necrosis factor （TNF）-a were detected by enzyme linked immunosorbent assay. Results Ghrelin prevented ventricular remodeling, increased PPAR-y expression in the myocardium, suppressed collagen I and collagen Ill mRNA expression, and also decreased the serum levels of TNF-a, but not CRP. All abovementioned effects of ghrelin were inhibited by GW9662. Conclusion Ghrelin inhibited ventricular remodeling induced by hypertension, and the preventive effects of ghrelin may be mediated by the anti-inflammatory actions of the PPAR-y-dependent pathway.

Anluohuaxianwan Alleviates Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through Upregulation of Peroxisome Proliferator-Activated Receptor-Gamma and Downregulation of Nuclear Factor-Kappa B/IκBα Signaling Pathway

Objective:The aim of this study was to investigate the effects of traditional Chinese medicine Anluohuaxianwan(ALHXW)on peroxisome proliferator-activated receptor-gamma(PPARγ)and nuclear factor-kappa B(NF-κB)signaling pathways using a rat model of carbon model groups were gavaged with saline for 6 weeks.Liver function was measured,and liver fibrosis and necroinflammation were assessed.Protein and messenger RNA expression levels of PPARγ,NF-κB,and Inhibitorαof NF-κB(IκBα)were analyzed by Western blot and reverse transcription–quantitative polymerase chain reaction.Results:ALHXW markedly alleviated liver injury compared with the model group,as indicated by the improvements in disease status,the morphology of liver and spleen,the liver and spleen indexes,and liver function.The extent of liver fibrosis was improved,hepatic stellate cell activation was inhibited,the expression of PPARγand IκBαwas significantly higher,and the expression of NF-κB was significantly lower in the treatment group as compared with the model group.Conclusions:ALHXW treatment can alleviate CCl4-induced liver fibrosis in rats, and the potential antifibrogenic mechanisms may occur through the upregulation of PPARγ expression and downregulation of NF-κB/IκBα signaling pathway.

Effect of dexamethasone on peroxisome proliferator activated receptor-gamma mRNA expression in 3T3-L1 adipocytes with the human recombinant adiponectin

Background The fat derived protein adiponectin plays an important role in the regulation of glucose metabolism. The aim of this study was to provide the experimental basis for further investigating on adiponectin （ADPN） function. Its eukaryotic recombinant was constructed and expressed in precursor cells of 3T3-L1 adipocytes. The effects of dexamethasone on peroxisome proliferator activated receptor-gamma （PPAR-y） mRNA expression in 3T3-L1 cells with human recombinant adiponectin were assessed. Methods The recombinant plasmid pMD18-T-hADPN and eukaryotic expression vector pcDNA3.1^＋ were digested by two restrictive endonucleases and adiponectin and linear pcDNA3.1^＋ were obtained. Then, they were ligated and translated into JM109. The recombinant pcDNA3.1^＋-hADPN so obtained was identified by digestion by restrictive endonuclease and nucleotide sequencing. The 3T3-L1 precursor cells were transfected using SuperFect Transfection Reagent （Qiagen）. Furthermore, 3T3-L1 cells with human recombinant adiponectin incubated with dexamethasone （0.5 mmol/L） for 24 hours, cells were collected and total RNA was extracted. The PPAR-γ mRNA expression was quantified by semiquantitative reverse transcription-polymerase chain reaction （RT-PCR）. Results After eukaryotic recombinant was digested by Hind Ⅲ and EcoR Ⅰ, fragments of 800 bp and 5.4 kb were identified by nucleotide sequence scanning and consistent with theoretical values. Electrophoretogram of RT-PCR in 3T3-L1 precursors showed only one band in front of 250 bp, which was consistent with theoretical value 234 bp. In the 3T3-L1 cells, 3T3-L1 cells with plasmid and 3T3-L1 cells human recombinant adiponectin, treatment with dexamethasone （0.5 mmol/L） decreased PPAR-y mRNA expression compared to untreated controls （P〈0.01）. Effect of dexamethasone on PPAR-γ mRNA expression in 3T3-L1 cells was reversed by stably transfected human recombinant adiponectin. Conclusion The 3T3-L1 cells stably transfected human recombinant adiponectin had increased PPAR-γ mRNA expression. Dexamethasone suppressed PPAR-γ mRNA expression in the 3T3-L1 cells. Effect of dexamethasone on PPAR-γ mRNA expression in 3T3-L1 cells was reversed by stably transfected human recombinant adiponectin.

Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology

Peroxisome proliferator-activated receptor gamma （PPARy） is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARy acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal （HPG） axis, and is reciprocally regulated by HPG. In the human, PPARγprotein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells （spermatocytes）. Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARy signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects.

Association between peroxisome proliferator-activated receptor-γ coactivator-1α gene polymorphisms and type 2 diabetes in southern Chinese population:role of altered interaction with myocyte enhancer factor 2C

Background Some single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptor-y coactivator （PGC）-1α gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1α and type 2 diabetes in the southern Chinese population and to determine whether the common variants： Gly482Ser and Thr394Thr, in the PGC-1α gene have any impacts on interaction with myocyte enhancer factor （MEF） 2C. Methods The SNPs in all exons of the PGC-1α gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism （PCR-SSCP） and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1α gene alter the interaction with MEF2C. Results Three frequent SNPs （Thr394Thr, Gly482Ser and Thr528Thr） were found in exons of the PGC-1α gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls （40.1% vs 29.3%, P〈0.01）. Even in controls, the 482Ser（A） carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly（G） carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr （A） had a synergic effect on the interaction between 482Ser variant and MEF2C. Conclusions The results suggested that the 482Ser variant of PGC-1α conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants （Gly482Ser, Thr394Thr） in the PGC-1α gene and MEF2C.

基于不同组织和器官角度回顾PGC-1α在运动抗衰老中的作用

背景:过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferators-activated receptors gamma co-activator 1α,PGC-1α)和衰老密切相关,且其在运动抗衰老中发挥着重要的调控作用,但缺乏从不同组织和器官视角下PGC-1α在运动抗衰老中作用的相关综述。目的:详细回顾PGC-1α在运动抗衰老中的作用,并从不同组织和器官的角度探讨其调控情况。方法:于2023-05-01/07-01进行文献检索。检索范围包括自各数据库建库至2023年7月,并在Web of Science、PubMed、中国知网、万方和维普数据库上进行检索。中文检索词:“PGC-1α,过氧化物酶体增殖物激活受体γ共激活因子1α,PPARGC1A,衰老,运动,老年人等”;英文检索词:“PGC-1α,aging,exercise,exercise training,older adults”。运用布尔逻辑运算符将检索词连接进行检索,并制定了相应的检索策略。根据纳入和排除标准进行筛选,最终纳入文献83篇进行综述分析。结果与结论:①PGC-1α是一个重要的转录共激活因子,在维持线粒体功能、调控能量代谢和适应不同代谢需求方面发挥着关键的调节作用。②在线粒体衰老中的多种功能,在多种细胞类型中的调节作用,在多种细胞类型中发挥着重要的调节作用,与炎症途径和氧化还原控制的关系及其相关蛋白修饰和表观遗传变化。③PGC-1α的表达水平能够被运动训练提高,并通过调节线粒体生物发生、能量代谢和抗氧化应激等途径发挥积极的作用,其在运动改善脂肪组织衰老、心血管老化、神经系统老化、肾脏衰老、骨骼肌衰老和肝脏老化等中发挥重要作用。④课题组专家建议未来研究方向包括探索不同类型、强度和时长的运动对PGC-1α表达的调节影响,研究PGC-1α的蛋白修饰和表观遗传变化的调节机制,以及加强对PGC-1α在不同衰老相关疾病中的作用机制的研究。

白藜芦醇通过SIRT1/PGC-1α影响牛肌管细胞线粒体生物发生和肌纤维类型转化

以牛肌管细胞为研究对象,通过添加白藜芦醇探究其对牛肌管细胞肌纤维类型转化的影响及其作用机制。通过噻唑蓝法和比色法对细胞活力和相关代谢酶活力进行测定,对成肌调节因子、肌球蛋白重链(myosin heavy chains,MyHCs)以及线粒体生物发生相关分子的基因和蛋白表达量进行测定。结果表明,白藜芦醇处理显著提高了Myf5、Myf6、MyoG和MyoD的基因表达水平(P<0.05),促进了牛肌管细胞分化。白藜芦醇处理显著提高了慢肌纤维蛋白(slow MyHC)的表达,降低了快肌纤维蛋白(fast MyHC)表达,同时上调了MyHC I和MyHC IIa基因表达水平,下调了MyHC IIx和MyHC IIb基因表达水平(P<0.05)。白藜芦醇还能显著提高牛肌管细胞中的琥珀酸脱氢酶和苹果酸脱氢酶活性,降低乳酸脱氢酶活性(P<0.05),此外,白藜芦醇显著提高了沉默信息调节因子1(silent information regulator 1,SIRT1)、过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptor-gamma coactivator-1α,PGC-1α)、核呼吸因子(nucleus respiratory factors,NRF)-1、线粒体转录因子A(mitochondrial transcription factor A,TFAM)的基因和蛋白表达水平(P<0.05)。添加SIRT1抑制剂6-氯-2,3,4,9-四氢-1H-咔唑-1-甲酰胺(1H-carbazole-1-carboxam,EX527)后,显著削弱了白藜芦醇诱导的肌纤维类型转化(P<0.05),白藜芦醇对SIRT1、PGC-1α、NRF-1和TFAM的基因和蛋白表达的促进作用被EX527显著削弱(P<0.05)。综上所述,白藜芦醇通过激活SIRT1/PGC-1α信号通路促进线粒体生物发生,进而促进牛肌管肌纤维类型的转化。

基于PPARγ信号通路研究香烟烟雾提取物干预不同时间下对肺泡巨噬细胞胞葬及吞噬功能影响的分子机制

目的:观察香烟烟雾提取物(CSE)干预不同时间下肺泡巨噬细胞胞葬及吞噬功能的变化,探讨其对肺部疾病炎症反应的影响及分子机制。方法:大鼠肺泡巨噬细胞NR8383采用10%CSE分别干预6 h、12 h、24 h、48 h,分为6 h空白对照组、6 h-10%CSE组、12 h空白对照组、12 h-10%CSE组、24 h空白对照组、24 h-10%CSE组、48 h空白对照组、48 h-10%CSE组。10%CSE干预12 h后联用PPAR抑制剂/激动剂,分为PPAR抑制剂组、PPAR激动剂组。Alamar Blue法检测PPAR激动剂对NR8383细胞增殖及毒性作用;流式细胞术检测NR8383细胞胞葬、吞噬功能及M1、M2极化分型;酶联免疫吸附实验检测TNF-α、TGF-β1、MFG-E8含量;免疫印迹法检测PPARγ信号通路及下游分子CD36蛋白表达;qPCR检测PPARγ、CD36 mRNA的表达。结果:10%CSE干预6 h后,NR8383细胞吞噬及胞葬功能均有所升高,PPARγ表达下调,CD36 mRNA表达增加,TNF-α、TGF-β1、MFG-E8表达均升高,但无明显极化方向;干预12 h,NR8383细胞吞噬功能及胞葬率显著降低,PPARγ、CD36表达显著下调,TNF-α表达增强,TGF-β1、MFG-E8表达降低,向M1型巨噬细胞极化;干预24 h后,NR8383细胞胞葬率降低,但吞噬大肠杆菌的功能增强,PPARγ表达下调,CD36蛋白表达降低,TNF-α表达降低但差异无统计学意义,TGF-β1、MFG-E8表达仍处于降低状态,有明显的M1型极化倾向;48 h后NR8383细胞胞葬率仍旧降低,但吞噬能力显著提升,PPARγ表达显著降低,CD36表达显著增加,TNF-α表达降低,TGF-β1、MFG-E8表达增加,巨噬细胞向M1、M2方向极化均增加。选择10%CSE干预12 h联合PPAR激动剂、抑制剂后发现,PPAR激动剂增强NR8383细胞胞葬及吞噬能力,上调PPARγ、CD36表达,抑制炎症因子TNF-α表达,促进抑炎因子TGF-β1、胞葬辅助因子MFG-E8表达。结论:随着CSE干预时间的变化,肺泡巨噬细胞从早期炎症反应的活化状态,逐渐进展为慢性炎症反应状态,进而导致肺泡巨噬细胞胞葬及吞噬功能障碍,该机制与PPARγ通路被抑制有关。

PPARγ在神经系统发育及相关疾病中的研究进展

过氧化物酶体增殖物激活受体γ (peroxisome proliferator-activated receptor gamma, PPARγ)作为配体依赖型核内转录因子,是经典的脂代谢调控因子,参与机体脂肪生成、葡萄糖代谢、血管生成和炎症发生等多种生物过程。除了在脂肪酸代谢活跃部位高水平表达, PPARγ在神经系统也大量存在,近年来越来越多的研究开始关注PPARγ在神经系统中扮演的角色。本文综述了PPARγ在神经系统发育及相关疾病发生发展中的重要作用:PPARγ通过调控机体炎症反应因子参与神经系统炎症过程;在中枢神经系统或周围神经系统发生外因损伤时, PPARγ通过抑炎或促进再生表现出神经保护功能;在帕金森病、阿尔茨海默病等神经退行性疾病中,调控PPARγ的表达可以起到延缓病程或临床治疗的效果;在视网膜病变中, PPARγ可以通过保护视网膜神经节细胞起到缓解作用。这些总结工作可以为PPARγ在神经系统发育和相关疾病进程中的调控机制研究及配体类药物开发提供参考资料。

Sestrin1参与调控小鼠肝脏细胞糖异生

目的研究应激诱导蛋白1(SESN1)在小鼠肝脏糖异生途径中的作用及调节机制。方法RT-qPCR检测SESN1在C57BL/6J小鼠禁食条件下肝脏组织以及用佛司可林(Fsk)与地塞米松(Dex)处理的原代肝细胞中的mRNA表达水平。通过质粒转染HepG2细胞,RT-qPCR检测SESN1过表达对糖异生相关基因PGC-1α,PEPCK,G6Pase的mRNA表达水平的影响。利用双荧光素酶报告系统研究SESN1在HepG2细胞中对PGC-1α的启动子活性的影响。在HepG2细胞中,通过过表达SESN1同时抑制SIRT1表达检测SESN1对PGC-1α去乙酰化状态的影响;通过敲低SIRT1表达检测其是否介导了SESN1诱导糖异生相关基因mRNA水平的变化。结果SESN1在饥饿的C57BL/6J小鼠肝脏组织和佛司可林(Fsk)和地塞米松(Dex)处理的原代肝细胞中的mRNA表达水平显著升高(P<0.001)。在HepG2细胞中过表达SESN1促进了PGC-1α,PEPCK,G6Pase的mRNA表达水平(P<0.001)并促进PGC-1α的启动子活性(P<0.001)。SESN1的过表达降低了原代肝细胞中PGC-1α的乙酰化水平,利用Sirt家族抑制剂NAM和shRNA腺病毒分别干扰SIRT1表达,均拮抗了SESN1对PGC-1α的去乙酰化作,同时SIRT1诱导的PGC-1α,PEPCK和G6Pase的表达也明显受损(P<0.0001)。结论SESN1参与调控小鼠肝脏细胞糖异生,可能依赖于SIRT1。

BRAF、TP53、Pax8-PPARγ在甲状腺癌中的表达及疗效预测价值

目的探讨肿瘤蛋白P53(TP53)、丝氨酸/苏氨酸蛋白激酶(BRAF)、配对盒基因8-过氧化物酶体增殖物激活受体γ(Pax8-PPARγ)在甲状腺癌中的表达及疗效预测价值。方法将2020年4月至2022年4月该院收治的150例甲状腺癌患者纳入研究。检测患者甲状腺癌组织及癌旁组织中TP53、BRAF、Pax8-PPARγmRNA的表达水平,分析其与临床病理因素的关系,基于受试者工作特征(ROC)曲线及决策曲线分析TP53、BRAF、Pax8-PPARγmRNA表达水平预测^(131)I治疗效果的价值。结果甲状腺癌组织中的TP53、BRAF、Pax8-PPARγmRNA表达水平高于癌旁组织(P<0.05)。甲状腺癌患者淋巴结转移、肿瘤最大径、包膜浸润与TP53、BRAF、Pax8-PPARγmRNA表达水平有关(P<0.05)。采用放射性^(131)I清除术后残留的甲状腺组织(简称清甲)失败患者组织TP53、BRAF、Pax8-PPARγmRNA表达水平均高于清甲成功患者(P<0.05)。ROC曲线分析显示,TP53、BRAF、Pax8-PPARγmRNA联合预测甲状腺癌患者清甲失败的曲线下面积优于三者单独预测(P<0.05)。决策曲线显示,三者联合预测甲状腺癌清甲失败发生的净收益率优于单一预测(P<0.05)。结论TP53、BRAF、Pax8-PPARγ在甲状腺癌组织中呈高表达,联合检测有助于预测^(131)I治疗效果,为临床确定合理治疗方案及时机提供参考。

过氧化物酶体增殖因子活化受体gamma激动剂抑制腭中缝扩张后骨重建

目的探讨过氧化物酶体增殖因子活化受体gamma(PPAR-γ)激动剂对腭中缝扩张(MSE)后骨重建的影响。方法应用雄性野生型C57BL/6小鼠共60只,分为假手术+正常饮食组;MSE+正常饮食组;MSE+匹格列酮饮食组。术后14d或28d处死,采用HE染色,实时荧光定量PCR方法研究匹格列酮对腭中缝扩张后骨重建的影响。结果 PPAR-γ激动剂匹格列酮减少腭中缝扩张手术后小鼠腭中缝成骨,并显著下调成骨细胞调控分子(Runx2和Dxl5)以及成骨细胞标志分子(COLIα1)的基因表达。结论在快速上颌扩大术后的腭中缝牵张成骨过程中,PPAR-γ激动剂匹格列酮抑制新骨形成;其机制可能是通过抑制成骨细胞的分化。

PPARγ基因沉默的人骨髓基质细胞对骨髓抑制小鼠造血功能的影响

目的 观察过氧化物酶体增殖激活受体γ(peroxisome proliferator activated receptor-gamma, PPARγ)基因沉默的人骨髓基质细胞HS-5对骨髓抑制小鼠造血功能的影响,并初步探讨其可能的作用机制。方法 用X射线进行全身照射构建骨髓抑制小鼠模型,造模后2 h,将小鼠随机分为3组,分别为实验组(尾静脉注射PPARγ RNAi干扰的HS-5细胞)、对照组(尾静脉注射未行PPARγ RNAi干扰的HS-5细胞)、空白组(尾静脉注射等量的生理盐水),每组5只。各组于放疗前、放疗后24 h、放疗后1周、放疗后2周进行外周血常规检测。对HS-5细胞在体外进行成骨、成脂诱导,分为实验组(PPARγ RNAi干扰的HS-5细胞)、对照组(未干扰PPARγ的HS-5细胞)、空白组(未行成骨/成脂诱导分化的HS-5细胞),观察成骨/成脂染色情况。采用CCK-8实验检测PPARγ基因沉默的HS-5细胞对小鼠骨髓造血干细胞(hemopoietic stem cell, HSC)增殖的影响,分为实验组(PPARγ RNAi干扰的HS-5细胞经成骨诱导分化3 d后,与小鼠HSC共培养)、阳性对照组(50μmol/L PPARγ抑制剂处理的HS-5细胞经成骨诱导分化3 d后,与小鼠HSC共培养)、阴性对照组(未干扰PPARγ的HS-5细胞经成骨诱导分化3 d后,与小鼠HSC共培养)、空白组(小鼠HSC单独培养,不与HS-5细胞共培养)。结果 放疗后,各组小鼠血常规指标均呈先降低后升高趋势,放疗后1周,三组小鼠血小板、白细胞水平差异显著,且实验组>对照组>空白组(均P<0.05);放疗后2周,三组小鼠脂肪空泡面积百分比差异显著,且实验组<对照组<空白组(均P<0.05),经Pearson相关分析显示,血常规各指标与血清PPARγ表达水平呈负相关(均P<0.05),与脂肪空泡面积百分比呈负相关(均P<0.05)。在体外成骨/成脂诱导分化后,实验组与对照组相比,橙红色的细胞比例明显降低,红色钙结节比例明显增高;成骨分化诱导3 d后,实验组、阳性对照组、阴性对照组人骨髓基质细胞均与小鼠HSC细胞进行共培养,空白组则单纯培养HSC细胞,结果显示共培养24、48、72 h后,实验组、阳性对照组小鼠HSC细胞增殖水平均高于阴性对照组和空白组(均P<0.05)。结论 PPARγ基因沉默的HS-5植入骨髓抑制小鼠后有助于小鼠造血功能增强。PPARγ基因被干扰沉默后,可增强HS-5细胞的成骨分化能力,减弱HS-5细胞的成脂分化能力,而成骨分化诱导的HS-5细胞能进一步增强小鼠HSC的增殖能力。

多囊卵巢综合征病人血清Ⅲ型纤连蛋白域蛋白5、过氧化物酶体增殖物激活受体γ辅助激活因子-1α水平与胰岛素抵抗的关系

目的探究多囊卵巢综合征(PCOS)病人血清Ⅲ型纤连蛋白域蛋白5(FNDC5)、过氧化物酶体增殖物激活受体γ辅助激活因子-1α(PGC-1α)表达水平与胰岛素抵抗的关系。方法选取2017年1月至2021年12月在重庆松山医院接受治疗的118例PCOS病人为PCOS组,另选取与PCOS病人年龄、身体质量指数(BMI)、腰臀比相匹配的同期健康体检者94例作为对照组。酶联免疫吸附测定(ELISA)检测两组血清FNDC5、PGC-1α表达水平;全自动生化分析仪检测空腹胰岛素(FINS)、空腹血糖(FBG)水平,并计算胰岛素抵抗相关指标胰岛β细胞功能指数(HOMA-β)和胰岛素抵抗指数(HOMA-IR);Pearson相关性分析研究病人血清FNDC5、PGC-1α水平与胰岛素抵抗相关指标之间的关系。结果与对照组相比,PCOS组FBG、FINS、三酰甘油(TG)、HOMA-β、HOMA-IR显著升高(P<0.05);与对照组相比,PCOS组FNDC5[(18.46±2.76)μg/L比(30.25±5.87)μg/L]、PGC-1α[(1.87±0.45)μg/L比(4.91±1.34)μg/L]表达水平显著降低(P<0.05)。Pearson相关性分析结果显示,PCOS病人血清FNDC5、PGC-1α水平均与FBG、FINS、HOMA-β、HOMA-IR呈显著负相关(P<0.05)。结论PCOS病人血清FNDC5、PGC-1α表达水平降低,与胰岛素抵抗存在负相关。

田蓟苷调节AMPK/SIRT1/PGC1α信号通路对脑出血大鼠认知功能和神经元损伤的影响

目的:探讨田蓟苷(TIL)对脑出血(ICH)大鼠认知功能、神经元损伤及腺苷酸激活蛋白激酶(AMPK)/沉默调节蛋白1(SIRT1)/过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC1α)信号通路的影响。方法:采用Ⅳ型胶原酶注射法构建ICH大鼠模型,将造模成功的ICH大鼠随机分为模型组(ICH组)、TIL组(16 mg/kg)、AMPK抑制剂组(Compound C组,250μg/kg)、TIL+AMPK抑制剂组(TIL+Compound C组),另设假手术组(Sham组),每组12只。采用改良的Garcia JH法、Morris水迷宫实验和敞箱实验评价大鼠的神经功能和认知功能;苏木素-伊红(HE)和脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法行脑组织病理学和神经元凋亡观察;蛋白质印迹法(Western Blot)检测AMPK/SIRT1/PGC1α通路蛋白表达。结果:与Sham组相比,ICH组大鼠脑组织出现细胞核皱缩、排列紊乱等损伤,神经功能评分、穿越平台次数、垂直活动得分和水平活动得分、磷酸化AMPK(p-AMPK)/AMPK、SIRT1、PGC1α蛋白水平均明显下降(P<0.05),找寻平台时间、神经元凋亡率、半胱氨酸蛋白酶-3(Caspase-3)、B淋巴细胞瘤-2(Bcl-2)蛋白表达水平均明显增加(P<0.05);与ICH组相比,TIL组大鼠脑组织损伤减轻,神经功能评分、穿越平台次数、垂直活动得分和水平活动得分、p-AMPK/AMPK、SIRT1、PGC1α蛋白水平均明显增加(P<0.05),找寻平台时间、神经元凋亡率、Caspase-3、Bcl-2蛋白表达水平均明显降低(P<0.05);而Compound C组大鼠以上指标呈现相反的趋势。且TIL对ICH大鼠脑组织及认知功能的保护作用均被AMPK抑制剂Compound C减弱(P<0.05)。结论:TIL可能通过激活AMPK/SIRT1/PGC1α通路,改善ICH大鼠认知功能,减轻神经元损伤。

破骨细胞过氧化物酶体增殖因子活化受体gamma敲除对腭中缝扩张后骨新生和骨重建的影响

目的探讨破骨细胞过氧化物酶体增殖因子活化受体gamma(PPAR-g)敲除对腭中缝扩张(MSE)后骨新生和骨重建的影响。方法将雄性对照野生型小鼠(WT)和破骨细胞PPAR-g敲除小鼠(KO)分为如下4组,WT+假手术,WT+MSE,KO+假手术,KO+MSE。术后14天处死,采用HE染色、抗酒石酸酸性磷酸酶(TRAP)染色、以及实时荧光定量PCR方法研究破骨细胞PPAR-g敲除对腭中缝扩张后骨新生和骨重建的影响。结果 KO+MSE组新骨形成面积较WT+MSE组增加,细胞总数增多,但是破骨细胞计数较WT+MSE组减少,破骨细胞分化相关基因(c Fos,Calcr,Car2,Ctsk,和Mmp9)的表达显著下降。结论破骨细胞PPAR-g敲除可以促进腭中缝扩张(MSE)后骨新生和骨重建。在腭中缝扩张后的骨重建过程中,PPAR-g是调控破骨细胞分化和骨新生的一个重要分子。

Down-regulated expressions of PPAR_γ and its coactivator PGC-1 are related to gastric carcinogenesis and Lauren's classification in gastric carcinoma

Objective： To explore the relationship between peroxisome proliferator activated receptor-gamma （PPARγ） and peroxisome proliferator-activated receptor-gamma coactivator-1 （PGC-1） expression in gastric carcinoma （GC）, and analyze their correlations with clinicopathological features and clinical outcomes of patients. Methods：The two-step immunohistochemical method was used to detect the expression of PPARγ and PGC-1 in 179 cases of GC, and 108 cases of matched normal gastric mucosa. Besides, 16 cases of fresh GC specimens and corresponding normal gastric mucosa were detected for PGC-1 expression with Western blotting. Results： The positive rates of PPART and PGC-1 expression were significantly lower in GC （54.75%, 49.16%） than in normal gastric mucosa （70.37%, 71.30%）, respectively （P〈0.05）. The decreased expression of PGC-1 in GC was confirmed ha our Western blot analysis （P=0.004）. PPAR7 and PGC-1 expressions were related to Lauren＇s types ofGC （P〈0.05）. Positive correlation was found between PPART and PGC-1 expression in GC （rk=0.422, P〈0.001）. The survival time of PPART negative and positive patients was 36.6±3.0 vs. 38.5_＋2.7 months, and no statistical difference was found between the 5-year survival rates of two groups （34.4% vs. 44.1%, P=0.522, log-rank test）; the survival time of PGC-1 negative and positive patients was 36.2±2.8 vs. 39.9±2.9 months, while no statistical difference was found between the 5-year survival rates of the two groups （32.0% vs. 48.2%, P=0.462, log-rank test） Conclusions＇. Decreased expression of PPARγand PGC-1 in GC was related to the Lauren＇s classification. Their expressions in GC were positively correlated, indicating that their fimctions in gastric carcinogenesis may be closely related.