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The present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
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Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.
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Improvement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease (COPD), but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture (EA) may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD.
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Objective To investigate whether physical training can activate the PI3K/Akt (phosphatidyli-nositol 3-kinase/Protein Kinase B) signal transduction pathway after focal brain isehemia, leading to the reduction ofendothelial cell apoptosis. Methods Twenty-four male adult Sprague-Dawley rats (2 ～ 3 month old, n = 24) weresubjected to 60-min right middle cerebral artery occlusion (MCAO). All rats were randomly assigned to one of thethree groups: physical training group, control group and sham operation group. 24 hours after MCAO ,physical train-ing group underwent 30 min treadmill training per day for 2 weeks. Results After two weeks, the phosphorylationlevel of PI3K/Akt in the physical training group was significantly higher when compared with that in the control group(P <0.05), while the expression level of Bax in physical training group was lower when compared with that in thecontrol group( P < 0.05 ). Conclusion Physical training can activate PI3K/Akt signal transduction pathway,which may be associated with the neurological recovery.
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@#Objective To observe the effect of fastigial nucleus stimulation(FNS)on heart rate variability(HRV)of surgically induced myocardial infarction rats.Methods 100 Sprague-Dawley rats were randomly allocated in four groups,including sham-operation control group,rats with coronary arteries ligated but fastigial nucleus(FN)sham stimulated(AMI group),rats both coronary arteries ligated and FN stimulated(FNS group),and rats on which FN lesioned 5 d before,then coronary arteries ligated and FN stimulated(FNL group).HRV characteristics were determined 6 h,1 d,7 d and 21 d after the ligation,and mortality rates were observed after 21 d.Results FNS can improve the survival of myocardial infarction rats,and this may be due to the increased vagal tone and decreased sympathetic tone.Conclusion FNS may have cardio-protective effects on surgically induced myocardial infarction rats.
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To investigate whether changes of amino acid neurotransmitter releases in the rostral ventrolateral medulla (rVLM) were related to acupuncture and to the antihypertensive effect of melatonin (Mel) microinjected into the anterior hypothalamic area (AHA) of rats with stress-induced hypertension (SIH), as well as to compare and analyze the relationship between the both antihypertensive mechanisms of acupuncture and of Mel in the AHA. Methods: Animal model of SIHR was made by electric foot shocks combined with noises. Electroacupuncture (EA) was used and Zusanli acupoint of both side was selected. The technique of drug microinjection into the brain was used to observe the change of blood pressure (BP), and synchronously, brain microdialysis was performed for collecting dialysate samples, and then the concentration of amino acid neurotransmitters in the dialysate samples was determined by high performance liquid chromatography combined with fluorescent detection (HPLC-FD). Results: After the animal received stress treatment, the BP elevated, synchronously, the release of glutamate (Glu) in the rVLM increased, and when EA was performed, the elevated BP of the rats with SIH decreased,simultaneously, the release of Glu in the rVLM decreased also. After Mel was microinjected of into the AHA of the SIHR, the elevated BP attenuated, meanwhile, the release of Glu decreased,and those of γ-aminobutyric acid (GABA) and taurine (Tau) increased in the rVLM.Administration ofbicuculline, an antagonist of GABAA receptor, into the rVLM prior to microinjection of Mel into the AHA could partially block the depressor effect of Mel in the AHA. Conclusion: The decrease in the release of Glu in the rVLM contributes to the antihypertensive effect of both acupuncture and Mel in the AHA in the rats with SIH, and the increase in the release of GABA and Tau in the rVLM is also important to Mel in the AHA.
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Objective:To investigate the mechanism of the reversal effect of acupuncture on the fall of blood pressure induced by angiotensin-(1-7)[Ang-(1-7)] in the caudal ventrolateral medulla(CVLM) of rats. Methods: Ang-(1-7) and its selective receptor antagonist (D-Ala7), Ang-(1-7) and Ang-(779) were microinjected into the CVLM respectively to induce the change of blood pressure, during which, the concentrations of amino acid neurotransmitters were detected by means of microdialysis and high performance liquid chromatography(HPLC)combined with fluorescent detector, on the other hand, the effects of electro-acupuncture (EA) on the level of blood pressure and the concentrations of amino acid neurotransmitters were also observed. Results:Unilateral microinjection of Ang-(1-7) into the CVLM could decrease the blood pressure (BP), which was accompanied by an increase in the release of Glu and a decrease in the release of Tau in the same site; Whereas microinjection of Ang-779 into the CVLM could elevate BP, which was accompanied by a decrease in the release of Glu and an increase in the release of Tau; EA at acupoint Zusanli (ST 36) for 20 min could inhibit the fall of blood pressure induced by microinjection of Ang-(1-7) into the CVLM and the elevation of blood pressure induced by microinjection of Ang-779 into the CVLM, and in the meantime, it could inhibit the changes of the release of Glu and Tau induced by microinjection of Ang-(1-7) and Ang-779 into the CVLM. Conclusion: The reversal effect of EA on the fall or elevation of blood pressure induced by microinjection of Ang-(1-7) or Ang-779 into the CVLM might be related to the changes of Glu and Tau release.
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Objective: The present study is to observe and compare the different effects of electroacupuncture(EA) at acupoint Neiguan (PC 6), intravenous administration of L-arginine(L-Arg, a precursor of nitric oxide), and the drug administration combined with the EA on acute myocardial ischemia(AMI) in rats. Methods: The rat model of AMI was established by occlusion of the anterior descending branch of the left coronary artery, then the animals were divided randomly into 5 groups,i.e. control group, AMI group, L-Arg treatment group, EA treatment group and L-Arg plus EA treatment group, the mean arterial pressure(MAP), heart rate(HR) and the cardiac functions were observed and recorded. Results: The data showed that MAP, HR and all the indices of cardiac functions in the AMI group were significantly lower than those in control group, and the indices in each treatment group were all improved to different extents, especially in L-Arg plus EA treatment group. Conclusion: The combined use of L-Arg and EA had the better therapeutic effect on the AMI.
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AIM: To isolate, purify and differentiate endothelial progenitor cells from cord blood in vitro and to study their biological characteristics. METHODS: CD133~+ cells were selected from fresh cord blood mononuclear cells (MNC) by magnetic activated cell-sorting system (MACS). EPC was studied by flow cytometry, immunocytochemistry and immunofluorescence staining. Isolated cells were cultured in IMDM medium supplemented with or without VEGF, bFGF, SCF. RESULTS: The percentage of CD133~+ cells of cord blood MNC was (1.41?1.14)%, and purity was 75%-85% (FACS method). CD133~+ cells were grown on fibronectin-coated chamber slides in the presence of VEGF, bFGF, SCF. Within 1-2 hours of culture cells became adherent. On day 7-10, the adherent cells displayed a typical "cobblestone" morphology. After 14 days of culture, the adherent cells revealed a heterogeneous cell population, comprising small-sized round cells, spindle-like cells and formed tube-like structure. Weibel-Palade bodies were shown on the transmission electron microscopy photomicrographs. Compared with the (original,) cell markers CD133 and CD34 decreased significantly (77.0%?3.3% to 1.6%?2.2% and 93.1%?4.7% to 37.4%?4.9%, P