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Objective Recent studies show that, tesaglitazar can reduce vascular plaque lipid deposition and inflammatory response in mice.This paper aims to investigate the effects of tesaglitazar, the peroxisome proliferator-activated receptor α/γ( PPARα/γ) agonist on serum lipid, serum nitric oxide ( NO) and heart type inducible nitric oxide synthase ( iNOS) mRNA expression in diabetic mice. Methods Thirty female 3-week-old clean grade mice were fed with ordinary adaptive diet for 7 days.The diabetic mouse model was established by feeding these mice with high-glucose-high-fat diet for four weeks and then taking small doses of streptozotocin( STZ) .These mice were randomly divided into two groups by means of ran-dom number table:control group and tesaglitazar group.Control group continued to be fed with high-glucose-high-fat diet, whereas te-saglitazar group was administered with tesaglitazar orally( high-glucose-high-fat fodder mixed with 20μg/kg tesaglitazar) .After 6 weeks′administration, body weight, total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipo-protein cholesterol(HDL-C) and blood glucose(Glu) levels were measured.Serum NO content were detected with nitrate reductase method, and the expression of iNOS mRNA in heart were detected by RT-PCR. Results Compared with control group[(3.62 ± 0.45)、(2.58 ±0.34)、(1.35 ±0.26)、(19.55 ±3.40) mmol/L], serum levels of TC、TG、LDL-C and Glu in tesaglitazar group [(2.93 ±0.38)、(1.87 ±0.41)、(1.07 ±0.30)、(14.33 ±2.08)mmol/L] were significantly decreased, difference was statistically significant(P<0.01).However, the levels of HDL-C were increased obviously campared with the control group[(1.32 ±0.21) mmol/L vs (1.05 ±0.24)mmol/L, P<0.01];The serum NO content in control group were significantly higher than that in tesaglita-zar group[(75.60 ±8.06)μmol/L vs (41.35 ±5.82)μmol/L] , difference was statistically significant(P<0.01); The ralative quantitative expression of iNOS mRNA in treatment group was significantly lower than that in control group[(0.435 ±0.064) vs (0.568 ±0.067)], difference was statistically significant(P<0.01). Conclusion Tesaglitazar can reduce the production of NO by means of inhibit excessive expressions of iNOS mRNA in diabetic mice.It can also improve the levels of serum lipid, and can delay the progression of atherosclerosis.
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[Abstract ] Objective Cardiac shock wave therapy (CSWT) can promote arteriogenesis in ischemic myocardia , but the mo-lecular mechanism remains unclear .The study aimed to explore the effect of CSWT on arteriogenesis in human cardiac microvascular endothelial cells ( HCMEC ) and the role of focal adhesion kinase (FAK) and Calcium-activated potassium channels (KCa) in the sig-nal conduction pathway of CSWT arteriogenesis . Methods HC-MEC cells cultured in vitro were randomly divided into control group , CSWT group , CSWT +T ( FAK inhibitor PF-573228 ) group and CSWT+F( SCa inhibitor iberiotoxin ) group.Each group received one CSWT(0.09 mJ/mm2, 200Times) 48 h after added stimulant.24 hours'conventional culture later , tests were made on the levels of endothelial nitric oxide synthase ( eNOS ) and vascular endothelial growth factor ( VEGF) mRNA as well as the changes of related protein expression . Results ①QPCR test showed that eNOS , VEGF mRNA expressions increased in CSWT group compared with control group (4.61 ±0.19 vs 3.99 ±0.17, P<0.05), while compared with CSWT group, eNOS, VEGF mRNA expressions in CSWT +T group were decreased (0.62 ±0.10 vs 0.40 ±0.02, P<0.05), eNOS, VEGF mRNA expressions in CSWT +F group were also decreased (0.53 ±0.02 vs 0.64 ±0.02, P<0.05), all the differ-ences were of statistical significance .②Western blot showed that eNOS , VEGF protein expressions increased in CSWT group compared with control group(0.63 ±0.02 vs 0.43 ±0.02, P<0.05), while compared with CSWT group , eNOS, VEGF protein expressions in CSWT+T group were decreased (0.36 ±0.01 vs 0.29 ±0.02, P<0.05), eNOS, VEGF protein expressions in CSWT +F group were also decreased (0.37 ±0.02 vs 0.30 ±0.02, P<0.05), all the differences were of statistical significance . Conclusion CSWT can improve eNOS , VEGF mRNA and protein expressions in HCMEC cells and FAK and KCa may participate in the signal conduction pathway of CSWT arteriogenesis .
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[ ABSTRACT] AIM:To investigate the protective effect of naringin ( Nar) on the injury of human umbilical vein endothelial cells ( HUVECs) induced by 33 mmol/L high glucose ( HG) and to explore its possible mechanisms.METH-ODS:The injury model was established by treating HUVECs with HG medium for the indicated time (6, 12, 24, 48 and 72 h) , and then the levels of NO, eNOS and p-eNOS were detected, respectively.The effects of Nar on high glucose-in-duced endothelial cell injury were observed.HUVECs were treated with Nar at concentrations of 5, 10, 25, 50 and 100 mg/L for 6 h, 12 h, 24 h, 36 h and 48 h.The levels of NO in the supernatants were measured.The effects of Nar on HG-injured HUVECs were explored by treating the cells with 10 μmol/L of LY294002, a PI3K inhibitor, or 0.5 μmol/L of AKT inhibitorⅣ, an AKT inhibitor, and then the levels of NO, PI3K, AKT, eNOS and their phosphorylated proteins were determined by Western blot.RESULTS:Nar at concentration of 50 mg/L significantly attenuated the injury of endothelial cells induced by high glucose ( P<0.01) , and the protective effects of Nar were abolished by pretreating with the inhibitor of PI3K or AKT (P<0.01).CONCLUSION: Nar protects endothelial cells against the injury induced by high glucose through PI3K/AKT/eNOS pathway.
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Objective To investigate alteration and cross link of the vascular endothelium dependent diastolic function (FMD) and platelet endogenous L-arginine/NOS/NO pathway before and after percutaneous coronary intervention (PCI) .Methods The study included two groups :normal control group(17 cases) and PCI group(20 cases) .FMD of brachial artery and NO production , NOS activity ,L-arginine transport in platelets were examined respectively before ,immediately ,24 h and 72 h after PCI and the rela-tionships between them would subsequently be analysed .Results The preoperative FMD ,content of NO2 - ,NOS activity and L-ar-ginine of PCI group significantly decreased than the normal control group (P0 .05) .The analysis showed the obvious positive correlation between FMD and content of NO2 - or NOS activity ,or L-arginine transport of platelet ,respectively(P<0 .01) .Conclusion The pathway of platelet L-arginine/NOS/NO was significantly positively correlated with FMD and the detection of platelet L-arginine/NOS/NO can reflect the changes of vascular endothelial function with PCI .
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Tumor target-derived soluble secretary factor has been known to influence macrophage activation to induce nitric oxide (NO) production. Since heme oxigenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress, we questioned whether soluble factor from tumor cells induces HO-1 through NO-dependent mechanism in macrophages. We designated this factor as a tumor-derived macrophage-activating factor (TMAF), because of its ability to activate macrophages to induce iNOS. Although TMAF alone showed modest activity, TMAF in combination with IFN-gamma significantly induced iNOS expression and NO synthesis. Simultaneously, TMAF induced HO-1 and this induction was slightly augmented by IFN-gamma. Surprisingly, however, induction of HO-1 by TMAF was not inhibited by the treatment with the highly selective iNOS inhibitor, 1400 W, indicating that TMAF induces the HO-1 enzyme by a NO-independent mechanism. While rIFN-gamma alone induced iNOS, it had no effect on HO-1 induction by itself. Collectively, the current study reveals that soluble factor from tumor target cells induces HO-1 enzyme in macrophages. However, overall biological significance of this phenomenon remains to be determined.