Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.

Role of Neuropeptide Y and Peroxisome Proliferator-activated Receptor γ Coactivator-1α in Stress Cardiomyopathy

Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.

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.

Down-regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression in fatty acid-induced pancreatic betacell apoptosis involves nuclear factor-κB pathway

Background Pancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid （PA） on the apoptosis and peroxisome proliferator-activated receptor y coactivator-1α （PGC-1α） expression in βTC3 cells as well as the possible role of nuclear factor-KB （NF-KB） in this process. Methods Hoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β （IKKβ）, IκBα NF-KB-inducing kinase （NIK） and ReI-B expressions were analyzed by Western blotting. MGβ2 was employed to block the endogenous IκBαdegradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed. Results Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA （0.5 mmol/L） could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods （0, 4, 6, 8, 10 and 12 hours）, IKKβ protein expression increased while IκBα NIK and ReI-B protein expression declined in a time-dependent manner. Pretreatment with MGβ2 to inhibit the degradation of IκBα partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis. Conclusions NF-KB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-KB pathway, so as to deteriorate the PA induced apoptosis.

PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.

胰腺癌细胞PANC-1中LSD1负向调控抑癌基因SIRT3的实验研究

背景与目的:组蛋白赖氨酸去甲基化酶1(lysine specific demethylase 1,LSD1)是重要的染色质修饰蛋白之一,可以通过调节染色质的结构调节基因的转录调控,进而影响肿瘤的发生、发展、侵袭、转移以及代谢异常等恶性潜能,是判断肿瘤预后的生物标志物。Sirtuins家族去乙酰化酶3(sirtuin3,SIRT3)基因是位于线粒体内的抑癌基因,通过调控肿瘤代谢异常以及氧化损伤行使抑癌基因的功能。本研究通过基因转录调控的手段,研究胰腺癌细胞PANC-1中LSD1与SIRT3的关系。方法:通过RNA干扰(RAN interference,RNAi)、免疫共沉淀(co-immunoprecipitation,CoIP)、染色质免疫共沉淀(chromatin immunoprecipitation assay,ChIP)及启动子活性分析等分子生物学实验手段,探讨LSD1与SIRT3在PANC-1细胞中的关系。结果:通过RNAi的手段干扰LSD1的表达,发现SIRT3基因转录水平和蛋白水平明显上升;通过蛋白相互作用的手段,发现LSD1可以与SIRT3转录调控的重要转录因子过氧化物酶增殖体激活受体辅激动子-1α(peroxisome proliferator-activated receptor gamma,coactivator 1 alpha,PGC-1α)相互作用;通过ChIP方法,发现LSD1与PGC-1α共同募集到SIRT3基因的启动子区域染色质上;通过启动子活性分析,发现LSD1基因可以显著抑制PGC-1α对SIRT3基因的转录调控。结论:LSD1可以表观遗传调控抑癌基因SIRT3的转录,为深入研究LSD1与肿瘤代谢异常以及氧化应激提供了理论依据。

Small interfering RNA targeting PGC-1α inhibits VEGF expression and tube formation in human retinal vascular endothelial cells

AIMTo determine whether small interfering RNA (siRNA) of PGC-1α could inhibit vascular endothelial growth factor (VEGF) expression and tube formation in human retinal vascular endothelial cells (hRVECs).METHODShRVECs transfected with peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) siRNA were incubated for 24h and then placed into a normoxic (20%, O2) or hypoxic (1%, O2) environment for another 16h. PGC-1α mRNA and protein levels were detected by real-time PCR and Western blot. VEGF mRNA and protein levels were detected by real-time PCR and ELISA. Cell proliferation was evaluated by BrdU incorporation assay. Forty-eight hours after siRNA transfection, hRVECs were planted into Matrigel-coated plates and cultured under normoxic (20%, O2) or hypoxic (1%, O2) conditions for another 48h. The tube formation of hRVECs was observed under an optical microscope and quantified by counting the number of branch points and calculating the total tube length.RESULTSPGC-1α mRNA and protein levels were significantly reduced by PGC-1α siRNA, and VEGF mRNA and protein levels also decreased significantly. The percentage of BrdU-labeled cells in siPGC-1α groups were significantly decreased compared with control siRNA groups under normoxia and hypoxia in cell proliferation assay. In the tube formation assay, PGC-1α siRNA treated cells formed significantly fewer tubes.CONCLUSIONBlocking PGC-1α expression can inhibit VEGF expression in hRVECs and inhibit their ability to form tubes under both normoxic and hypoxic conditions.

Effectiveness of sub-maximal intermittent exercise on muscle glycogen depletion, PGC-1<i>α</i>and PDK-4 gene expression

Several metabolic gene expressions are regulated in concert with muscle glycogen status. We hypothesized that intermittent exercise performed at high but sub-maximal intensities with long recovery periods would induce a low glycogen state that would stimul- ate peroxisome proliferator-activated receptor-γ coa- ctivator-1α (PGC1-α) and pyruvate dehydrogenase kinase-4 (PDK-4) gene expression in muscle. Nine young human subjects performed two intermittent exercise sessions. One session consisted of 60 s cycling bouts at VO2max (IE100%), and the other session consisted of 75 s cycling bouts at 80% VO2max (IE80%). Twelve bouts of exercise were completed in both sessions with a 4 min rest between each bout. Muscle specimens were obtained at pre-exercise and immediately, 1.5 h and 3 h post-exercise. Muscle gly- cogen was significantly decreased after both sessions (IE100%, 94.1 ± 5.8 to 38.7 ± 5.5 mmol/kg w.w.;IE80%, 94.6 ± 9.1 to 53.3 ± 4.8 mmol/kg w.w.;both P α and PDK- 4 mRNA expression were significantly increased after exercise in both IE100% and IE80% (PGC-1α: ~3.7 and ~2.9-fold, respectively;PDK-4: ~11.1 and ~3.5-fold, respectively;all P 100% than in IE80% (P a and PDK-4 mRNA expression, suggesting that increasing exercise intensity contributes to muscle glycogen depletion and PDK-4 mRNA expression in human skeletal muscle.

Danqi Tablet(丹七片)Regulates Energy Metabolism in Ischemic Heart Rat Model through AMPK/SIRT1-PGC-1α Pathway

Objective To investigate the cardioprotective effect of Danqi Tablet(DQT,丹七片)on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α).Methods Rat ischemic heart model was induced by ligation of left anterior descending coronary artery.Totally 40 Sprague-Dawley rats were randomly divided into sham group,model group,DQT group(1.5 mg/kg daily)and trimetazidine(TMZ)group(6.3 mg/kg daily)according to a random number table,10 rats in each group.Twenty-eight days after continuous administration,cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining.The level of adenosine triphosphate(ATP)in myocardial cells was measured by ATP assay kit.Expressions level of key transcriptional regulators,including PGC-1α,Sirtuin 1(SIRT1),AMP-activated protein kinase(AMPK),and downstream targets of PGC-1α,such as mitofusin 1(MFN1),mitofusin 2(MFN2)and superoxide dismutase 2(SOD2)were measured by Western blot.Expression level of PGC-1αwas examined by immunohistochemical staining.Results The rat ischemic heart model was successfully induced and the heart function in model group was compromised.Compared with the model group,DQT exerted cardioprotective effects,up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues(P<0.01).The expressions of PGC-1α,SIRT1 and AMPK were increased in the DQT group(all P<0.05).Furthermore,the downstream targets,including MFN1,MFN2 and SOD2 were up-regulated(P<0.05 or P<0.01).Compared with the TMZ group,the expression levels of PGC-1α,MFN1 and SOD2 were increased by DQT treatment(P<0.05 or P<0.01).Conclusion DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1-PGC-1αpathway.PGC-1αmight serve as a promising target in the treatment of ischemic heart disease.

Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins

Background:Recent studies have shown that mediator complex subunit 1(Med1)can significantly affect hepatocyte proliferation and differentiation.Acting as a tumor suppressor,microRNA-637(hsa-miR-637)can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis.However,the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated.Methods:This study used co-immunoprecipitation(Co-IP)assay,transfection,luciferase reporter assay,functional assay by cell counting kit-8(CCK-8),Annexin V-FITC/propidium iodide apoptosis assay,and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation(ChIP)for analysis.Results:Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors,identified as the peroxisome proliferator-activated receptor alpha(PPARA)and thyroid hormone receptor alpha(THRA)at the transcriptional and translational levels in the human liver HL-7702 cell line.The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed.The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated.Moreover,hsamiR-637 has been determined to suppress the proliferation of HL-7702 cells.Furthermore,cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase,but its apoptosis failed.Finally,PPARA was indicated to directly bind to the promoter of some transcription factors,like bcatenin,mouse double minute 2(MDM2),and p53.Conclusions:This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration,which may contribute in understanding the regenerative process of the liver.

Forensic Significance of Messenger RNA and Protein Expression of Genes Downstream of Hypoxia Inducible Factor 2 in Myocardial Tissue for Death Discrimination

Background: As a heterodimeric transcription factor, hypoxia-inducible factor 2 alpha subunit (HIF2A), is an important member of the HIF family. It plays a significant role in the hypoxia adaptation process by regulating the different types of downstream transcription factors and auxiliary regulatory factors. HIF2A-related factors are believed to participate in the progression of myocardial injury or myocardial ischemia, support the protection of ischemic myocardium, and provide guiding significance for the diagnosis and discrimination of sudden cardiac death in forensic pathology. Aim and Objectives: This study aimed to explore the discriminability and applicability of HIF2A-related factors in myocardial infarction cases compared with other causes of death, provide further insights for the forensic diagnosis of heart failure (HF) cases with myocardial infarction, and support the clinical treatment of patients with HF after myocardial infarction. Materials and Methods: The relative expression levels of HIF2A, amphiregulin (AREG), potassium large conductance calcium-activated channel subfamily M β1 (KCNMB1), peroxisome proliferator-activated receptor α (PPARA), vascular endothelial growth factor (VEGF), and VEGFR2 messenger RNAs (mRNAs) in myocardial tissue samples were performed using quantitative reverse transcriptase-polymerase chain reaction. A partial least squares-discriminant analysis model was constructed to select the indicators with better identification effects for myocardial infarction cases. The protein levels of HIF2A, AREG, KCNMB1, and PPARA were further detected by immunohistochemistry. The forensic autopsy cases (27 cases in total, postmortem interval <72 h) included seven cases of acute myocardial infarction and ten cases of myocardial ischemia. There were ten cases in the control group, including four cases of traffic injury, one case of injury by fall from height, and five cases of blunt force injury. Results: Characteristic results were observed in the myocardial ischemia/infarction samples. Compared with the control group, the relative mRNA expression levels of AREG, KCNMB1, and PPARA were significantly increased during the progression of myocardial ischemia, but this was not observed for HIF2A, VEGF, or VEGFR2 mRNA. Immunohistochemistry assays further verified the expression levels of the related factors at the protein level, and H and E staining showed signs of angiogenesis and inflammation in the ischemia/infarction group. Conclusions: By controlling the expression of downstream target genes (AREG, KCNMB1, and PPARA) during myocardial cell hypoxia adaptation, HIF2A has a potential significance in the diagnosis of myocardial infarction in forensic medicine. We believe that HIF2A, AREG, KCNMB1, and PPARA can be used as molecular pathological biomarkers for the discrimination of causes of death in myocardial infarction cases.

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-lnduced Cardiac Hypertrophy

Background：Shensong Yangxin Capsule （SSYX）,traditional Chinese medicine,has been used to treat arrhythmias,angina,cardiac remodeling,cardiac fibrosis,and so on,but its effect on cardiac energy metabolism is still not clear.The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin （Ang） Ⅱ-induced cardiac hypertrophy.Methods：We used 2 μl （10-6 mol/L） AngⅡ to treat neonatal rat cardiomyocytes （NRCMs） for 48 h.Myocardial α-ac tinin staining showed that the myocardial cell volume increased.Expression of the cardiac hypertrophic marker-brain natriuretic peptide （BNP） messenger RNA （mRNA） also increased by real-time polymerase chain reaction （PCR）.Therefore,it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed.Then,NRCMs were treated with 1 μl of different concentrations of SSYX （0.25,0.5,and 1.0 μg/ml） for another 24 h.To explore the time-depend effect of SSYX on energy metabolism,0.5 μg/ml SSYX was added into cells for 0,6,12,24,and 48 h.Mitochondria was assessed by MitoTracker staining and confocal microscopy.mRNA and protein expression of mitochondrial biogenesis-related genes-Peroxisome proliferator-activated receptor-γ coactivator-1 α （PGC-1 α）,energy balance key factor -adenosine monophosphate-activated protein kinase （AMPK）,fatty acids oxidation factor-camitine palmitoyltransferase-1 （CPT-1）,and glucose oxidation factor-glucose transporter-4 （GLUT-4） were measured by PCR and Western blotting analysis.Results：With the increase in the concentration of SSYX （from 0.25 to 1.0 μg/ml）,an increased mitochondrial density in Angll-induced cardiomyocytes was found compared to that of those treated with Angll only （0.25 μg/ml,18.3300 ± 0.8895 vs.24.4900 ± 0.9041,t =10.240,P 〈 0.0001;0.5 μg/ml,18.3300 ± 0.8895 vs.25.9800 ± 0.8187,t =12.710,P 〈 0.0001;and 1.0 μg/ml,18.3300 ± 0.8895 vs.24.2900 ± 1.3120,t =9.902,P 〈 0.0001;n =5 per dosage group）.SSYX also increased the mRNA and protein expression ofPGC-1α （0.25 μg/ml,0.8892 ± 0.0848 vs.1.0970 ± 0.0994,t =4.319,P =0.0013;0.5 μg/ml,0.8892 ± 0.0848 vs.1.2330 ± 0.0564,t =7.150,P 〈 0.0001;and 1.0 μg/ml,0.8892 ± 0.0848 vs.1.1640 ± 0.0755,t =5.720,P 〈 0.0001;n =5 per dosage group）,AMPK （0.25 μg/ml,0.8872 ± 0.0779 vs.1.1500 ± 0.0507,t =7.239,P 〈 0.0001;0.5 μg/ml,0.8872 ± 0.0779 vs.1.2280 ± 0.0623,t =9.379,P 〈 0.0001;and 1.0 μg/ml,0.8872 ± 0.0779 vs.1.3020 ± 0.0450,t =11.400,P 〈 0.0001;n =5 per dosage group）,CPT-1 （1.0 μg/ml,0.7348 ± 0.0594 vs.0.9880 ± 0.0851,t =4.994,P =0.0007,n =5）,and GLUT-4 （0.5 μg/ml,1.5640 ± 0.0599 vs.1.7720 ± 0.0660,t =3.783,P =0.0117;1.0 μg/ml,1.5640 ± 0.0599 vs.2.0490 ± 0.1280,t =8.808,P 〈 0.0001;n =5 per dosage group）.The effect became more obvious with the increasing concentration of SSYX.When 0.5 μg/ml SSYX was added into cells for 0,6,12,24,and 48 h,the expression of AMPK （6 h,14.6100 ± 0.6205 vs.16.5200 ± 0.7450,t =3.456,P =0.0250;12 h,14.6100 ± 0.6205 vs.18.3200 ± 0.9965,t =6.720,P 〈 0.0001;24 h,14.6100 ± 0.6205 vs.21.8800 ± 0.8208,t =13.160,P 〈 0.0001;and 48 h,14.6100 ± 0.6205 vs.23.7400 ± 1.0970,t =16.530,P 〈 0.0001;n =5 per dosage group）,PGC-1α （12 h,11.4700 ± 0.7252 vs.16.9000 ± 1.0150,t =7.910,P 〈 0.0001;24 h,11.4700 ± 0.7252 vs.20.8800 ± 1.2340,t =13.710,P 〈 0.0001;and 48 h,11.4700 ± 0.7252 vs.22.0300 ± 1.4180,t =15.390;n =5 per dosage group）,CPT-1 （24 h,15.1600 ± 1.0960 vs.18.5800 ± 0.9049,t =6.048,P 〈 0.0001,n =5）,and GL UT-4 （6 h,10.2100 ± 0.9485 vs.12.9700 ± 0.8221,t =4.763,P =0.0012;12 h,10.2100± 0.9485 vs.16.9100± 0.8481,t=1 1.590,P〈 0.0001;24 h,10.2100±0.9485 vs.19.0900± 0.9797,t=15.360,P〈 0.0001;and 48 h,10.2100 ± 0.9485 vs.14.1900 ± 0.9611,t =6.877,P 〈 0.0001;n =5 per dosage group） mRNA and protein increased gradually with the prolongation of drug action time.Conclusions：SSYX could increase myocardial energy metabolism in AngⅡ-induced cardiac hypertrophy.Therefore,SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.

软骨细胞线粒体生物发生在骨关节炎发病机制中的作用

目的总结软骨细胞线粒体生物发生在骨关节炎(osteoarthritis,OA)发病机制中的作用并分析其应用前景。方法查阅近年国内外相关文献,对线粒体生物发生在OA病程中的变化、在OA软骨细胞中主要信号分子的作用,以及在OA治疗中的应用前景进行总结。结果近年研究发现线粒体是软骨细胞的重要能量代谢中心,其功能障碍被认为是OA发生、发展的重要机制。线粒体生物发生是维持线粒体正常数量和功能的关键生物过程之一,过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptor-gamma coactivator 1 alpha,PGC-1α)是该过程的关键调控因子。现已报道了以PGC-1α为中心,腺苷酸活化蛋白激酶、沉默信息调节因子1/3及环磷酸腺苷反应元件结合蛋白等为主要上游调控分子,核呼吸因子1、雌激素受体α、核呼吸因子2等为主要下游调控分子的线粒体生物发生调控网络。然而,软骨细胞线粒体生物发生在OA发病机制中的作用还需进一步深入探索。已有研究表明如葛根素、人网膜素-1等药物和活性物质可通过激活OA软骨细胞中受损的线粒体生物发生过程延缓OA发生、发展,为OA治疗提供了新思路。结论软骨细胞线粒体生物发生在OA发病机制中起重要作用,进一步探索相关机制具有重要临床意义。

Sirtuins Function as the Modulators in Aging-related Diseases in Common or Respectively

INTRODUCTIONAccording to the demographics, the world population over 60 years will double from 605 million to 2 billion people between 2000 and 2050. Aging is a complex process in which the organism and its ability to respond to external stresses become progressive decline.