Objective To investigate the effects of adenosine 2A receptor (A2AR) activation on oxidative stress in small-forsize liver transplantation. Methods A rat orthotopic liver transplantation model was performed using 40% graft, 18 recipients were given intravenously saline (control group), CGS21680 (A2AR agonist, CGS21680 group) or ZM241385 (A2AR antagonist, CGS21680+ZM241385 group) randomly. Aspartate aminotransferase (AST), enzymatic antioxidants 〔superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GSH-Px)〕, non-enzymatic antioxidants 〔ascorbic acid (AA); glutathione (GSH); α-tocopherol (TOC)〕 and lipid oxidant metabolites malondialdehyde (MDA) were measured and analyzed at 6 h after reperfusion. Results Compared with the control group and CGS21680+ZM241385 group, A2AR activation increased the activities of SOD and GSHPx (Plt;0.05), reduced the productions of AST and MDA (Plt;0.05), increased the levels of AA, GSH and TOC (Plt;0.05) in CGS21680 group. But there was no significant change in CAT activity (Pgt;0.05) among 3 groups. Conclusions A2AR activation improves the antioxidant enzyme activities, promotes the production of antioxidants, and slowes down the increase in MDA level, depresses of the increase in AST activity. A2AR activation suppresses oxidative damage and increases the antioxidant capacity which in turn minimizes their harmful effects of ischemia-reperfusion in small-for-size liver transplantation.
Objective To investigate the value of adenosine deaminase (ADA) for the diagnosis of tuberculous serous cavity fluidify. Methods The literatures on the application of ADA for the diagnosis of tuberculous serous cavity fluidify in the database including PUBMED and CNKI were reviewed. Results Studies including randomized controlled trial or meta-analysis have performed to determine the level of ADA in the effusion of tuberculous serous cavity fluidify. These studies have sufficiently proved that ADA is a specific and sensitive method for the diagnosis of extrapulmonary tuberculosis. Most of the studies have determined the optimal cut-off value of ADA in the effusion of tuberculous serous cavity fluidify. Conclusion Measurement of ADA in the effusion of tuberculous serous cavity fluidify is widely used as a fast, convenient, safe and effective adjunctive diagnostic method of tubeculosis in clinic.
Adenosine activated protein kinase (AMPK) is a serine/threonine protein kinase that can sense the change of intracellular energy. AMPK plays a critical part in the occurrence and development of tumors. According to the difference of AMPK catalytic subunits, it is divided into AMPKα1 and AMPKα2. The AMPKα1 subunit is the catalytic subunit of AMPK and is extensively distributed in the various tissues and organs. This review focuses on the structural, activated and functional aspects of AMPKα1 and the involvement of AMPKα1 in the regulation of intracellular substance metabolism, and summarizes the respective performances of AMPKα1 in different cancers and the corresponding potential applications of AMPKα1 as a drug target in the relevant cancers. AMPKα1 can be used as a diagnostic marker or drug target for cancer diagnosis and therapy, providing an idea for cancer treatment, which has importance clinical significance.
Objective To investigate the changes and roles of myocardial adenosine triphosphate enzyme(ATPase) in the mechanism of cardiac dysfunction after blunt chest trauma（BCT）. Methods Thirtysix rabbits were divided into 6 groups with random number table, control group, 2 h group, 4 h group, 8 h group, 12 h group and 24 h group, 6 in each group. The models of BCT were established with BIMⅡ biological impact machine, catheterization technique was used through the right jugular artery into the left ventricle measure its pressure. The hemodynamics and the activities of ATPase in myocardial cell plasm, homogenate and mitochondria were measured at preinjury(control group), 2 h, 4 h, 8 h, 12 h and 24 h postinjury. Results Left ventricular endsystolic pressure(LVESP), the maximal ascending rate of left intraventricular pressure(+dp/dtmax), isovolemec pressure(IP) and the maximal physiological velocity(Vpm) decreased significantly at 2 h group after BCT(Plt;0.05）, and recovered to preinjury level in 4 h, 8 h and 12 h group during 4-12 h after BCT; isovolumic relaxation phase left ventricular pressure descending time constant (T). Left ventricular enddiastolic pressure(LVEDP) and the maximal descending rate of left intraventricular pressure(-dp/dtmax) were significantly higher （Plt;0.05, 0.01）. The activity of ATPase in homogenate, mitochondria and cell plasm decreased significantly at 2 h group and 4 h group after BCT（Plt;0.05, 001, respectively）, and 8 h group and 12 h group recovered after BCT. There was negative correlations between [CM(159mm]LVEDP and -dp/dtmax and the decrease of the activity of Na+-K+-ATPase in homogenate（r=-0.674, -0.691, Plt;0.05）, the Ca2+-ATPase in homogenate（r=-0.613,-0.642, Plt;0.05）, the Na+-K+-ATPase in mitochondria（r=-0.622,-0.616, Plt;0.05）,the Ca2+-ATPase in myocardial cell plasm（r=-0.672,-0.658, Plt;0.05）, the Na+-K+-ATPase in myocardial cell plasm（r=-0.627,-0.632,Plt;0.05）,and the Mg2+-ATPase in myocardial cell plasm（r=-0.677,-0.661, Plt;0.05）. Conclusion The left ventricular function is impaired obviously after BCT, especially in diastolic phase. The decrease of the activity of ATPase in myocardial cells may be one of the reasons of cardiac dysfunction after BCT.
Objective To investigate the effect of adiponectin on proliferation of airway smooth muscle cells( ASMCs) , and explore its possible mechanism. Methods ASMCs were derived fromrat airway tissue and were cultured in vitro. RT-PCR was used to verify the expression of adiponectin receptors on ASMCs. Then ASMCs were treated with adiponectin at different concentrations( 5, 10, 20, 40, 80 μg/mL) for different periods of time( 1, 12, 24, 48, 72 hours) , respectively. The absorbsence ratios of adiponectin at different concentrations were determined by MTT assay. The adenosine monophosphate-activated protein kinase( AMPK) and phosphorylated AMPK( pho-AMPK) in ASMCs were quantified by Western blot after being treated with adiponectin at different concentrations ( 5, 10, 20, 40 μg/mL) for 48 hours. ResultsThe inhibition of adiponectin on ASMCs was showed in dose-dependent manner( r = 0. 324, P lt; 0. 01) and time-dependent manner( r = 0. 607, P lt; 0. 05) . Western blot indicated that the expression of pho-AMPK increased with the increased concentrations of adiponectin( r =0. 607, P lt; 0. 01) . The ratio of pho-AMPK/AMPK were ( 27. 66 ±1. 03) % , ( 31. 91 ±0. 86 ) %, ( 75. 52 ±2. 67) % , and ( 84. 50 ±1. 05) % ,respectively, with significant differences between each concentrations of adiponectin( P lt; 0. 05) . There was no expression of pho-AMPK in the control group. Conclusion Adiponectin can significantly inhibit ASMCs’proliferation by activating AMPK.
Objective To investigate the mechanism of adenosine-tri phosphate (ATP) activated mammal ian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signal pathway in the physiology and pathology of spinal cord injury (SCI). Methods Ninety-six adult healthy female Sprague-Dawley rats were randomly divided into 4 groups (groups A, B, C and D, n=24). In groups A, B and C, the rats were made the SCI models at T8-10 levels by using a modified Allen’ s stall, and in group D, rats were given laminectomy without SCI. The rats were subjected to the administration of ATP (40 mg/kg) for 7 days in group A, to the administration of physiological sal ine (equal-volume) for 7 days in group B, to the administration of ATP (40 mg/kg) and rapamycin (3 mg/kg) for 7 days in group C, and to the administration of physiological sal ine (equal-volume) for 7 days in group D. Locomotor activity was evaluated using the Basso-Beattie-Bresnahan rating scale at the postoperative 1st, 2nd, 3rd, and 4th weeks. Then, the expressions of spinal cord cell marker [Nestin, neuron-specific enolase (NSE), gl ial fibrillary acidic protein (GFAP)] and the mTOR/STAT3 pathway factors (mTOR, STAT3) were detected at the postoperative 1st, 2nd, 3rd, and 4th weeks by immunohistochemistry analysis, Western blot assay, and real-time fluorescence PCR analysis. Results The BBB scores in group A showed a steady increase in the postoperative 1st-4th weeks and were significantly higher than those in groups B and C (P lt; 0.01), but were lower than that in group D (P lt; 0.01). Real-time fluorescence PCR results showed that the mRNA expressions of mTOR, STAT3, NSE of group A steadily increased, however, the Nestin mRNA expression gradually decreased in the postoperative 1st-4th weeks, which were all significantly higher than those of groups B, C, and D (P lt; 0.01). The mRNA expression of GFAP showed a steady increase in group A and was significantly less than those of groups B and C, but was higher than that of group D (P lt; 0.01). There were significant differences (Plt; 0.01) in all markers between groups B, C, and group D; there were significant differences in mTOR, P-mTOR, STAT3, and P-STAT3 mRNA between groups B and C at 1st-4th weeks (P lt; 0.05). The similar changes were found by Western blot assay. Conclusion ATP can activate the mTOR/STAT3 pathway to induce endogenic NSCs to prol iferate and differentiate into neurons in rats, it enhances the heal ing of SCI.
ObjectiveTo explore the relationship between mitochondrial function and the severity of sepsis by detecting the platelet mitochondrial permeability transition pore, transmembrane potential and adenosine triphosphate (ATP) levels in peripheral blood. MethodsAccording to random number table, 40 male SD rats were randomly divided into three sepsis model groups (group A, B and C) and a sham group (group D). The rats in the model groups received cecal ligation and puncture (CLP) treatment with different percent of ligated length in total length of the cecum (10% in group A, 30% in group B and 50% in group C, respectively). Twenty-four hours later, peripheral blood was collected for TNF-α, IL-1βand IL-6 levels determination, also the mitochondrial permeability transition pore, transmembrane potential and ATP content were tested in the isolated platelet. One-way ANOVA test was used to determine the relevance between above indices and the severity of sepsis. Meanwhile, 29 patients with sepsis were enrolled for clinical study. After APACHEⅡscoring, platelet samples of peripheral blood in the patients were collected for mitochondrial function determination. The relationship between mitonchondrial function and APACHEⅡscore was analyzed by Spearman method. ResultsCalcein fluorescence, membrane potential and ATP synthesis in platelet mitochondria of the rat sepsis model were gradually decreased with the increased severity of CLP, and the difference among these groups were all statistically significant (all P < 0.05). In clinical specimens, APACHEⅡscore was negatively correlated with ATP level of platelet mitochondria(r=-0.895, P < 0.05). ConclusionMitochondrial function of platelet in peripheral blood can be used as an effective indicator for the severity of sepsis.
Objective To evaluate the inhibiting effect of adenosine on rat retinal ganglion cells (RGC) death induced by P2X7 and N-methyl-D-aspartate (NMDA) receptor. Methods (1) Long-Evan neonatal rats were back labeled with aminostilbamidine to identify RGC. The viability of RGC affected by P2X7 excitomotor BzATP (50 mu;mol/L), glutamate receptor excitomotor NMDA (100 mu;mol/L) and adenosine (300 mu;mol/L) was detected. (2) RGC from the retinae of unlabeled neonatal rats were cultured in vitro. After labeled with Fura-2 methyl acetate, an intracellular calcium indicator, the effect of BzATP, NMDA and adenosine on intracellular Ca2+ level was detected byCa2+ imaging system. Results Both BzATP (50 mu;mol/L) and NMDA(100 mu;mol/L) could kill about 30% of the RGC. Cell death was prevented by adenosine (300 mu;mol/L) with the cell viability increased from (68.9plusmn;2.3)% and (69.9plusmn;3.2)% to (91.2plusmn;3.5)% (P＜0.001) and (102.1plusmn;3.9)% (P＜0.001), respectively. BzATP (50 mu;mol/L) led to a large, sustained increase of intracellular Ca2+ concentration to (1183plusmn;109) nmol/L. After the adenosine intervened, Ca2+ concentration increased slightly to (314plusmn;64) nmol/L (P＜0.001). Conclusion Adenosine may prevent RGC death and increase of intracellular Ca2+ concentration from P2X7and NMDA receptor stimulation. (Chin J Ocul Fundus Dis, 2007, 23: 133-136)
Epilepsy is a complex disease spectrum, because of long-term recurrent seizures and seriously affect the quality of life of patients, it is of great significance to explore the pathogenesis of epilepsy and actively seek new therapeutic targets. In this paper, the pathogenesis of epilepsy related to mitochondrial pathway was discussed from the aspects of energy depletion, oxidative stress damage, impaired calcium homeostasis, increased glutamic acid release, mitochondrial DNA mutation, Coenzyme Q10 deficiency, abnormal mitochondrial movement and change, and relevant therapeutic ideas were proposed. This paper shows that mitochondrial function affects the onset of epilepsy from various ways. Further understanding of the relationship between mitochondria and the onset of epilepsy is beneficial to find new therapeutic targets and develop new therapies beyond the control of epilepsy.
Objective To study the distribution of P2 Y2 receptor in spine cord, dorsal root ganglia and sciatic nerve in rat, and to provide the basis for clarifying the mechanism of the effect of adenosine triphosphate(ATP) on the peripheral nerve regeneration. Methods Six specimens of the spine cord, dorsal root ganglia and sciatic nerve from SD rats were fixed rapidly in 4% paraformaldehyde which included DEPC, imbedded by paraffin and made into ultrathin section. According to the sequence of P2 Y2 receptor’s gene, DNA needle was adopted to detect the distribution of P2 Y2 receptor by hybridization technique in section under the light microscope after theyhad been stained in NBT liquid（50 mg/ml） and BCIP liquid （75 mg/ml）. In thecontrol group, the ultrathin section was only covered with hybridism buffer solution. The result of staining was observed. ResultsHybridization in section showed that P2 Y2 receptor was distributed mainly in the anterior horn cell of spine cordgray matter and Schwann cell of the dorsal root ganglia. No P2 Y2 receptor was observed in the sciatic nerve of both groups. Conclusion P2 Y2 receptor is located mainly in the spine cord and the dorsal root ganglia. Extracellular ATP can affect the cell of spine cord, dorsal root ganglia through P2 Y2 receptor.