Objective To investigate the protective effects and molecular mechanism of peroxisome proliferate-activated receptor α(PPARα) activation on acute myocardial damage induced by isoproterenol (Iso) in rats. Methods Thirty male Wistar rats, weighting 160～180 g, were randomly divided into control group, Iso group, fenafibrate(FF) group(each n=10) according to physique quantity. Acute myocardial injury caused by Iso abdomen cavity injection induced ischemia was established and the protective effects of peroxisome proliferate-activated receptor α activation were accessed by the level of ereatine kinase(CK), lactic dehydrogenase(LDH) in serum as well as the activities of myoperoxidase(MPO) in myocardium, and the protein expressions of PPABα in myocardium by Western blot. Results The level of serum CK in control group, lso group and FF group, was (62.41±9.47),(101.71±11.05),(75.64±11.73)kU/L, respectively(F= 34.34, P<0.01). Whereas the level of serum CK in Iso group and FF group was higher than that in control group(P<0.01 or<0.05), the level of serum CK in FF group was lower than that in Iso group(P<0.01). The levels of LDH in these three groups were (5912.20±204.44), (6365.78±137.10), (6089.76±169.60) U/L, respectively(F= 17.54, P<0.01). Compared with the control group, the levels of LDH in Iso and Fir groups were significantly increased(P<0.01 or<0.05). But the level of LDH in FIr group was decreased compared with that in Iso group(P<0.01). The activities of myocardial MPO in these three groups were (1.95±0.10),(3.89±0.17),(2.49±0.19)U/g, espectively(F=391.68,P< 0.01). The activities of myocardial MPO in Iso and FF groups were higher than that in the control group (all P< 0.01), while the activities of myocardial MPO in FIr group were lower than that in lso group(P<0.01). The protein expressions of PPARα in myocardium of these three groups were 251.57±10.95,191.97±10.74,215.08±9.61, respectively(F=82.69, P<0.01). Conclusion PPARα activation by its actor FF can exert protective effects on the acute myocardial ischemia injury induced by lso in rats through inhibiting the release of inflammatory cell factors.

BACKGROUNDPeroxisome proliferator-activated receptor (PPAR) alpha is one of the subtypes of PPARs. It regulates metabolism of lipid and lipoprotein, as well as glucose homeostasis. In addition, PPARalpha influences cellular proliferation, inflammation, differentiation and apoptosis, which plays a vital role in cardiovascular diseases. The purpose of this study was to investigate the role and mechanisms of PPARa activation in relation to acute myocardial damage induced by isoproterenol in rats.

METHODSThirty male Wister rats were randomly divided into control group, isoproterenol (Iso) injured group and fenofibrate (FF) treatment group. Acute myocardial damage caused by isoproterenol intraperitoneal injection induced ischemia was established. We determined the levels of creatine kinase (CK) and lactic dehydrogenase (LDH) in serum as well as the concentrations of free fatty acids (FFA) in serum and myocardium. The mRNA expressions of PPARa, muscular type carnitine palmitransferase (M-CPT-I) and medium chain lipid acetyl coenzyme A dehydrogenase (MCAD) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSCompared with the control group, the levels of serum CK and LDH were significantly increased after FF and Iso treatments. Moreover, the concentrations of FFA in both serum and myocardium were obviously increased in the Iso group and FF group, while the mRNA expressions of PPARalpha, M-CPT-I and MCAD declined, respectively (P < 0.01). When compared with the Iso group, significant decreases in serum CK and LDH were observed in the FF group. The concentrations of FFA both in serum and myocardial tissue were markedly decreased in the FF group, while the expressions of PPARalpha, M-CPT-I and MCAD mRNA were increased (vs. Iso, P < or = 0.01).

CONCLUSIONSThe utilization of FFA was reduced in isoproterenol induced acute myocardial damage. PPARalpha activation by its activator fenofibrate may play a key role in energy metabolism in acute myocardial damage induced by isoproterenol in rats.

Animals ; Creatine Kinase ; blood ; Energy Metabolism ; Fatty Acids, Nonesterified ; metabolism ; Fenofibrate ; pharmacology ; Heart ; drug effects ; Isoproterenol ; toxicity ; L-Lactate Dehydrogenase ; blood ; Male ; PPAR alpha ; physiology ; Rats ; Rats, Wistar

Objective To observe the effects of peroxisome pmliferator-activated receptor(PPAR)α agonist Fenofibrate (FF) on energy metabolism and histology in isoproterenol (Iso) induced acute myocardial ischemie injury modeL Methods Male Wistar rats were randomly divided into control group.Iso group(5 ms/kg,I.p) and FF group (80 mg·kg-1·d-1 per gavage for 7 days,then Iso 5 mg/ks,I.p.n=30 each).Twenty-four hours post Iso,heart weight/body weight ratio,myocardial histopathological changes (HE staining),serum and myocardial free fatty acids(FFA)levels,the myocardial protein expression of PPAR (Westem blot) were determined.Result Compared with the control group,pathological myocardial injuries were observed under light microscope in Iso treated hearts and FF pretreatment could significantly attenuate these changes [necrotic area:O VS(10.004±3.00)% VS(7.36±2.60)%],the heart weight/body weight ratio,FFA in serum (501.17±43.69 VS 939.53±69.51 v8 736.53 4±70.30 mol/L)and myocardium(62.01±9.19 VS 140.59 4±19.34 VS 116.28 4±14.03 mol/L) were significantly increased while myocardial protein expressions of PPAR (251.57 4±10.95 VS 191.97±10.74 VS 215.08±9.61) was significantly downregulated in the Iso group and FF pretreatment could significantly attenuate these changes (all P<0.05).Condusion Our data suggested that the FFA utilization wag decreased in Iso induced acute myocardial ischemic injury and FF could attenuate Iso induced myocardial damage via activating PPAR signaling pathway.

OBJECTIVETo evaluate the potential role of hepatocyte growth factor (HGF) combined with bone marrow mesenchymal stem cells (BMSC) autograft for the treatment of silicosis.

METHODSBone marrow (100 ml) was aspirated from a severe silicosis patient. BMSCs isolated, purified and cultured in vitro. When BMSC came to 70% confluence at passage 3, the culture medium was added liposomes (lipo2000) and plasmid-HGF (p-HGF) and cultured for 2 d. HGF-MSCSs (5 × 10(7) cells) were resuspended in 50 ml 0.9% sodium chloride (NS) and infused Intravenous drip at 3 consecutive times (once a week). Clinical follow-up were performed before and after treatment: (1) pulmonary high-kV X-ray, chest CT examination; (2) pulmonary function test; (3) determination of serum ceruloplasmin.

RESULTSThe symptoms such as coughing, chest tightness disappeared at 12 months after treatment. Pulmonary function tests showed significant changes after treatment: forced vital capacity (FVC) increased from 64.6% to 81.0%, forced expiratory volume in one second (FEV(1.0)) increased from 68.7% to 90.1%, 1 second rate (FEV(1.0)/FVC%) reduced from 111.6% to 107.1%, the maximum mid-expiratory flow (FEF(25%∼75%) decreased from 100.2% to 94.6%, forced expiratory vital capacity 75% of the moment bit of gas flow (MEF(75%)) increased from 99.2% to 113.5%, forced expiratory vital capacity 50% of the moment bit of gas flow (MEF(50%)) increased from 125.3% to 130.2%, forced expiratory vital capacity 25% of the moment bit of gas flow (MEF(25%)) reduced from 86.9% to 71.7%; serum ceruloplasmin levels decreased from 690 mg/L to 180.6 mg/L; lung high-kV X-ray at 1st review showed that diffuse lung nodules had been absorbed and getting smaller than before treatment; chest CT showed that the distribution and number of small nodules at double lung fields decreased than before treatment.

CONCLUSIONHGF combined with BMSC transplantation may have some potential role for the treatment of silicosis patients.

Adult ; Bone Marrow Transplantation ; Female ; Follow-Up Studies ; Hepatocyte Growth Factor ; therapeutic use ; Humans ; Mesenchymal Stem Cell Transplantation ; Silicosis ; therapy ; Treatment Outcome

To investigate the time-course changes of myogenic tone in mesenteric small artery (MSA) of spontaneously hypertensive rat (SHR), thirty-two 7-week aged SHR rats were randomly divided into four groups (8, 16, 24, 32 weeks of age), and 32 sex- and age-matched Wistar-Kyoto (WKY) rats were assigned to control groups (CON). On the day of the study, segments of MSA were isolated and then cannulated to the two pipettes. Vascular diameters in response to the increased intraluminal pressure (from 0 mmHg to 150 mmHg, by 25 mmHg steps) of isolated MSA under no-flow conditions were recorded by a Pressure Myograph System both in physiologic salt solution (PSS) (active diameter, Da) and calcium-free PSS (passive diameter, Dp). The myogenic tone was calculated by (Dp - Da)/Dp × 100%. The tail artery pressure and vascular myogenic tone in SHR rats were significantly higher than those of the CON rats. Before 24 weeks, the vascular myogenic tone of MSA in SHR group increased monotonically, but at the end of 32 weeks, the vascular myogenic tone decreased in comparison with that in 24-week group, but was significantly higher than that in CON group. The tail artery pressure in SHR group slowly increased monotonically with increasing weeks of age, and the tail arterial pressure in 32-week group remained significantly higher than that in 24-week group. Vascular myogenic tone may participate in the whole process of hypertension. Early in the development of hypertension, because of the compensatory role of vascular tone, the vascular function has been partially compensated, thus guaranteeing adequate blood supply to organs. Late in the development of hypertension, because of the decompensation of myogenic tone, the vascular function is damaged, leading to the occurrence of severe vascular disease.
Animals ; Blood Pressure ; Hypertension ; physiopathology ; Male ; Mesenteric Arteries ; physiopathology ; Muscle Tonus ; Muscle, Smooth, Vascular ; physiopathology ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Time Factors ; Vasoconstriction ; physiology

AIMTo investigate the effects of ramipril on myocardial ischemia/reperfusion injury in diabetic rats, and to explore its mechanism according to the observation on myocardial ultrastructure.

METHODSStreptozotocin induced diabetic rats were divided randomly into three groups (n = 16): ischemia/reperfusion (I/R), ischemic preconditioning (IPC) and ramipril (RAM) group. Rats in RAM group were administered by RAM(1 mg x kg(-1) x d(-1)) orally for 4 weeks, the others were administered by normal saline. Then all rats were subjected to myocardial ischemia/ reperfusion injury. Rats in IPC group were preconditioned before ischemia. The ECG and the infarct size were examined. The changes of myocardial morphology were examined by light and electron microscopes.

RESULTSCompared with I/R group, the elevation of ST segment and the incidence of ventricular tachycardia and ventricular fibrillation during ischemia were significantly decreased, the infarct size at the end of reperfusion was remarkably reduced, the myocardial morphology were significantly improved, special structure of myofilaments and mitochondria remained clearly, blood vessels were unobstructed, injury of endothelium were decreased in PC and RAM groups.

CONCLUSIONRamipril administered for 4 weeks induces myocardial protection in diabetic rats, which is similar to that of IPC. The mechanism may be involved in protection of cardiocytes and mitochondria, and improvement of endothelial function.

Animals ; Cardiotonic Agents ; pharmacology ; Diabetes Mellitus, Experimental ; complications ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Reperfusion Injury ; pathology ; prevention & control ; Myocardium ; ultrastructure ; Ramipril ; pharmacology ; Rats

Background: Intermittent hypoxia (IH) is a key element of obstructive sleep apnea (OSA) that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 (CYP) and CYP regulators, including nuclear receptors. Methods: Hematoxylin and eosin staining was conducted to analyze the general pathology of the liver of rats exposed to IH. The messenger RNA (mRNA) expression levels of inflammatory cytokines, CYPs, nuclear factor?κB (NF?κB), and nuclear factors in the liver were measured by quantitative reverse transcription polymerase chain reaction. Results: We found inflammatory infiltrates in the liver of rats exposed to IH. The mRNA expression level of interleukin?1beta was increased in the liver of the IH?exposed rats (0.005 ± 0.001 vs. 0.038 ± 0.008, P = 0.042), whereas the mRNA expression level of Cyp1a2 was downregulated (0.022 ± 0.002 vs. 0.0050 ± 0.0002, P = 0.029). The hepatic level of transcription factor NF?κB was also reduced in the IH group relative to that in the control group, but the difference was not statistically significant and was parallel to the expression of the pregnane X receptor and constitutive androstane receptor. However, the decreased expression of the glucocorticoid receptor upon IH treatment was statistically significant (0.056 ± 0.012 vs. 0.032 ± 0.005, P = 0.035). Conclusions: These results indicate a decrease in expression of hepatic CYPs and their regulator GR in rats exposed to IH. Therefore, this should be noted for patients on medication, especially those on drugs metabolized via the hepatic system, and close attention should be paid to the liver function of patients with OSA?associated IH.

Objective: The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba (AJH) on hepatoma carcinoma (HCC). Methods: In this study, ethanol extract of AJH was prepared and used to treat HCC cell in vitro. Furthermore, a genomic wide RNA sequencing (RNA-seq) was performed to screen deregulated genes in HCC cells after the treatment of AJH extract. The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq. Results: AJH extract could inhibit HCC cell proliferation in vitro. RNA-seq analysis has identified 1,601 differentially expressed genes (DEGs, fold change ≥ 2.0 or fold change ≤ 0.5, P < 0.05) in HCC after AJH extract treatment, which included 225 up-regulated genes and 1,376 down-regulated genes. KEGG pathway analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treatment. In agreement with the RNA-seq data, qPCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism (SREBP1, ACC, ACLY and FASN) were significantly down-regulated in AJH treatment group as compared with the control group. Furthermore, AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells. Conclusion: Ethanol extract of AJH could inhibit HCC cell proliferation in vitro, the possible mechanism may be related to the inhibition of lipid metabolism.

OBJECTIVETo investigate the effect of atrial fibrillation on the accuracy of parameters monitored by transpulmonary thermodilution method.

METHODSTotally 12 patients from emergency intensive care unit with paroxysmal atrial fibrillation were enrolled. The hemodynamic parameters such as heart rate, mean arterial pressure, cardiac index, systemic vascular resistance index, intrathoracic blood volume index, and extravascular lung water index were monitored by transpulmonary thermodilution method before paroxysmal atrial fibrillation and during atrial fibrillation, the number of B-lines was detected by lung ultrasonography before and during paroxysmal atrial fibrillation. The changes of all the parameters were analyzed.

RESULTSWhen the paroxysmal atrial fibrillation happened, the heart rate increased significantly [(123.3±20.0) beat/min vs. (98.9±12.3) beat/min, P=0.006]; the mean arterial pressure [(86.9±10.2) mmHg vs. (93.0±12.5) mmHg, P=0.058], cardiac index [(2.82±0.62) L/(min·m(2)) vs. (3.31±1.02) L/(min·m(2)), P=0.058] and systemic vascular resistance index [(2254±947) dyn·s·cm(-5)·m(2) vs. (2302±828) dyn·s·cm(-5)·m(2), P=0.351] had no obvious change; however, the intrathoracic blood volume index significantly increased [(1333±90) ml/m(2) vs. (937±111) ml/m(2), P<0.001]; extravascular lung water index also increased significantly [(16.1±1.1) ml/kg vs. (6.5±1.9) ml/kg, P<0.001]. No significant difference was found in the number of B-lines detected by lung ultrasonography before and during atrial fibrillation (10.0±4.2 vs. 9.4±4.4, P=0.180).

CONCLUSIONBoth intrathoracic blood volume and extravascular lung water monitored by transpulmonary thermodilution method were overvalued during paroxysmal atrial fibrillation, which may mislead the clinical judgment and decision-making.

Atrial Fibrillation ; physiopathology ; Blood Pressure ; Blood Volume ; Cardiac Output ; Extravascular Lung Water ; Heart Rate ; Hemodynamics ; Humans ; Intensive Care Units ; Thermodilution ; Vascular Resistance

Objective:To observe the effects of Fushengong prescription on p38 mitogen-activated protein kinase（p38 MAPK） signal pathway of rats with chronic renal failure（CRF），and to explore its mechanism of reducing inflammatory reaction of renal tissues and delaying the progress of renal interstitial fibrosis. Method:The 55 male Sprague-Dawley rats were randomly divided into normal group，model group， and low，medium and high dose groups of Fushengong prescription，with 11 rats in each group.The normal group was routinely reared， and the other four groups of rats were fed a diet containing 0.5% adenine to produce a model of CRF， which was continuously molded for 21 days.After successful modeling，all rats switched to conventional feed.Normal group and model group were given normal saline 20 mL·kg^-1，and each group of Fushengong prescription was given 4，8，16 g·kg^-1 of water prescription once a day for 30 days.After the experiment，Masson staining was used to observe the degree of renal interstitial fibrosis.The expression of monocyte chemotactic protein-1（MCP-1） in renal tissues was detected by immunohistochemistry. The expression of phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK） and transformed growth factor-β₁（TGF-β₁） in renal tissues were detected by Western blot. Result:Compared with normal group，the renal interstitial collagen deposition increased significantly，the average optical density value of MCP-1 and the expression levels of p-p38 MAPK and TGF-β₁ also increased significantly in model group （P<0.05）. Compared with model group，the renal interstitial collagen deposition reduced significantly，the average optical density value of MCP-1 and the protein expression levels of p-p38 MAPK and TGF-β₁ also decreased significantly in each dose group of Fushengong prescription（P<0.05）. Conclusion:Fushengong prescription can effectively inhibit the expression of related inflammatory factors in the renal tissue of CRF rats，so as to reduce the inflammatory response in the renal tissue and delay the progress of renal interstitial fibrosis，the mechanism of which may be related to inhibit the activation of p38 MAPK signal transduction pathway.