Lactato y catecolaminas: respuesta fisiológica en el paciente crítico / Lactate and catecholamines: a physiological response in critically ill patients

RESUMEN El lactato es un metabolito altamente dinámico que, en condiciones anaerobias, es producido por hipoxia o isquemia; y en condiciones aerobias, es sintetizado por un mecanismo impulsado por la estimulación adrenérgica, a través del receptor β2, que potencia la acción de la bomba sodio-potasio, y por un estado de glicólisis aerobia acelerada. Este metabolito es capaz de intercambiarse entre diferentes células productoras y consumidoras, con lo que asegura la materia prima para obtener energía. El sistema nervioso simpático responde a los estímulos de estrés con la liberación de catecolaminas, que actúan como hormonas y como neurotransmisores en varios tejidos del cuerpo y permiten un aumento del metabolismo que eleva los valores de glucosa y el oxígeno disponible. Existe una relación fisiológica de dependencia entre las catecolaminas y la producción de lactato que predispone al organismo para responder de forma efectiva ante una situación de estrés. Sin embargo, en tejidos sensibles, la respuesta adrenérgica exacerbada puede ocasionar efectos exagerados que pueden incrementar la probabilidad de fallo. En base al conocimiento de estos mecanismos, se plantean estrategias terapéuticas enfocadas en regular la actividad simpática.

ABSTRACT Lactate is a highly dynamic metabolite that is produced, under anaerobic conditions, due to hypoxia or ischemia. Under aerobic conditions, it is synthesized by a mechanism driven by the stimulation of the β2 adrenergic receptor, which increases the activity of the sodium-potassium pump, and by a state of accelerated aerobic glycolysis. This metabolite is capable of being exchanged between different producing and consuming cells, ensuring the raw material for energy production. The sympathetic nervous system responds to stress stimuli through the release of catecholamines, which act as hormones and neurotransmitters in various tissues of the body, allowing an increase in metabolism that raises glucose and available oxygen levels. There is a physiological dependence between catecholamine levels and lactate production, predisposing the body to respond effectively to a stressful situation. However, an exacerbated adrenergic response may cause exaggerated effects on sensitive tissues that increase the probability of failure. Based on the knowledge of these mechanisms, therapeutic strategies focused on regulating the sympathetic activity are proposed.

Effects of gene polymorphisms of β1 adrenergic receptor G1165C and A145G locus on myocardial hypertrophy and the efficacy in patients with hypertension / 中国医师进修杂志

Objective:To investigate the effect of gene polymorphism of β1 adrenergic receptor (β1-AR) G1165C and A145G locus on myocardial hypertrophy and the efficacy in patients with hypertension.Methods:Two hundred and twenty-seven cases of patients with hypertension admitted to Binhai County People′s Hospital from January to December 2019 were enrolled. Among them, there were 113 cases of hypertension with myocardial hypertrophy and 114 cases of hypertension without myocardial hypertrophy. In addition, 115 patients with normal physical examination during the same period were selected as the control group. DNA in the peripheral blood leukocytes was extracted, polymerase chain reaction-restriction fragment length polymorphism method was used to detect β1-AR G1165C and A145G locus gene polymorphism, and the differences in the efficacy of β blockers in hypertensive patients with different genotypes were compared.Results:There was no statistically significant differences in the distribution of β1-AR A145G genotypes among the three groups ( P>0.05). Compared with the healthy control group, the frequency of Gly/Gly genotype carrying β1-AR G1165C locus was higher in hypertension with myocardial hypertrophy group, and the frequency of Gly/Arg and Arg/Arg gene were lower; compared with hypertension without myocardial hypertrophy group, the frequency of Gly/Arg+Gly/Gly gene in hypertension with myocardial hypertrophy group was higher; taking Arg/Arg genotype as the control group, carrying Gly/Gly genotype could increase the risk of cardiac hypertrophy in hypertensive patients by 3.159 times ( OR = 3.159, 95% CI 1.240 - 7.412, P<0.05).The frequency of G1165C allele Arg in the hypertension with myocardial hypertrophy group was significantly lower than that in the control group and the hypertension without myocardial hypertrophy group ( P<0.05); the frequency of G1165C allele Gly was significantly higher than that in the control group and the hypertension without myocardial hypertrophy group ( P<0.05); taking Arg/Arg genotype as the control, carrying Gly/Gly genotype could increase the risk of cardiac hypertrophy in hypertensive ( OR = 3.417, 95% CI 1.357 - 7.965, P<0.05). The left ventricular mass index of Gly/Gly genotype patients was (120.38 ± 28.41) g/m 2, which was significantly higher than (99.76 ± 25.16) g/m 2 and (90.30 ± 19.54) g/m 2 of Gly/Arg and Arg/Arg, with statistically significant differences ( F = 10.89, P<0.01). After the treatment, the resting heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure of patients with G1165C allele Arg hypertension with myocardial hypertrophy were lower than those with G1165C allele Gly, with statistically significant differences ( P<0.05). Conclusions:β1-AR G1165C gene polymorphism is related to the risk of myocardial hypertrophy in hypertensive patients. Carrying the G1165C allele Gly may increase the risk of susceptibility to cardiac hypertrophy, and β-blockers are more effective in hypertensive patients with myocardial hypertrophy who carry the G1165C allele Arg.

Association between beta-2 adrenergic receptor variants and clinical outcomes in children and adolescents with acute asthma

ABSTRACT Objective To investigate whether different genotypes of p.Arg16Gly, p.Gln27Glu, p.Arg19Cys and p.Thr164Ile variants interfere in response to treatment in children and adolescents with moderate to severe acute asthma. Methods This sample comprised patients aged 2 to 17 years with a history of at least two wheezing episodes and current moderate to severe asthma exacerbation. All patients received multiple doses of albuterol and ipratropium bromide delivered via pressurized metered-dose inhaler with holding chamber and systemic corticosteroids. Hospital admission was defined as the primary outcome. Secondary outcomes were changes in forced expiratory volume in the first second after 1 hour of treatment, and for outpatients, length of stay in the emergency room. Variants were genotyped by sequencing. Results A total of 60 patients were evaluated. Hospital admission rates were significantly higher in carriers of the genotype AA relative to those with genotype AG or GG, within the p.Arg16Gly variant (p=0.03, test χ2, alpha=0.05). Secondary outcomes did not differ between genotypes. Conclusion Hospital admission rates were significantly higher among carriers of the genotype AA within the p.Arg16Gly variant. Trial registration: ClinicalTrials.gov: NCT01323010

Beta-adrenergic pathway activation in head and neck cancer: a comprehensive analysis of the clinical and genomic features using integrated bioinformatics / Ativação da via beta-adrenérgica no câncer de cabeça e pescoço: uma análise abrangente das características clínicas e gênomicas utilizando a bioinformática

O estresse crônico leva à ativação da via de sinalização beta-adrenérgica. Sua ativação tem sido implicada na progressão de diferentes tipos de câncer, mas seu papel nos carcinomas espinocelulares de cabeça e pescoço (CECPs) permanece indefinido. O objetivo deste estudo foi investigar o papel da ativação da via betaadrenérgica na progressão dos CECPs, avaliar seu impacto na sobrevida dos pacientes e buscar possíveis terapias para pacientes que encontravam-se com a via beta-adrenérgica ativa. Quinhentos e vinte pacientes do The Cancer Genome Atlas com CECPs primários foram divididos em dois grupos: ADRB2baixa / SLC6A2baixa e ADRB2alta / SLC6A2alta. A associação de características clinicopatológicas e genômicas entre os grupos foram analisadas utilizando bioinformática. Os genes diferencialmente expressos (DEGs) foram identificados através da análise da expressão diferencial. A análise de sobrevida também foi realizada com base nas expressões ADRB2 e SLC6A2. Foram identificados medicamentos em potencial para tratamento de CECPs com base nos DEGs. Houve associação entre as expressões ADRB2 e SLC6A2 com idade, raça, localização do tumor, grau histológico, invasão perineural e status do HPV p16. Foram identificados 898 DEGs entre os grupos. Foi demonstrado que a expressão ADRB2alta / SLC6A2alta influenciou a proliferação, adesão e invasão de células CECPs além da angiogênese. Pacientes com carcinomas espinocelular de laringe e faringe apresentando expressão ADRB2alta / SLC6A2alta tiveram menor sobrevida. Por fim, 56 drogas antineoplásicas e imunoterápicas aprovadas pelo Food Drugs Administration foram identificadas como potenciais alvos para o tratamento personalizado. Significância: Estes achados sugerem fortemente um papel proeminente da sinalização beta-adrenérgica no CECPs ao estimular um fenótipo tumoral mais agressivo. Estas alterações tiveram um impacto negativo no prognóstico dos pacientes com CECP em região de faringe e laringe(AU)

Chronic stress leads to the activation of the beta-adrenergic pathway. Its activation has been implicated in the progression of different types of cancer but its role on head and neck squamous cell carcinomas (HNSCCs) remains undefined. The aim of this study was to investigate the influence of the beta-adrenergic pathway activation in the progression of HNSCCs, assess its impact in the survival of the patients, and explore the potential targets. Five hundred and twenty The Cancer Genome Altas patients with primary HNSCCs were divided in two groups: ADRB2low / SLC6A2low and ADRB2high / SLC6A2high. The association of clinicopathological and genomic features between the groups was analyzed using a bioinformatic approach. Differentially expressed genes (DEGs) were identified through differential expression analysis. Survival analysis was also performed based on ADRB2 and SLC6A2 expressions. Potential drugs for treatment of HNSCC were identified based on the DEGs. There was association between ADRB2 and SLC6A2 expressions with age, race, tumor site, histologic grade, perineural invasion, and HPV p16 status. It was identified 898 DEGs between the groups. It was demonstrated that ADRB2high / SLC6A2high expression influenced HNSCC cells proliferation, adhesion, invasion, and angiogenesis. Patients with larynx and pharynx squamous cell carcinomas presenting ADRB2high / SLC6A2high expression showed had lower survival rates. Finally, 56 Food Drugs Administration-approved antineoplastic and immunotherapeutic drugs were identified as potential targets for the personalized treatment. Significance: These findings strongly suggest a prominent role of beta-adrenergic pathway in HNSCC by stimulating a more aggressive tumoral phenotype. These alterations were shown to negatively impact the prognosis of patients with larynx and pharynx squamous cell carcinomas(AU)

Relationship between sevoflurane-induced cognitive impairment and α1B and α1D adrenoceptors in cerebral cortex of rats / 中华麻醉学杂志

Objective To evaluate the relationship between sevoflurane-induced cognitive impairment and α1B adrenoceptors (ADRA1B) and ADRA1D in the cerebral cortex of rats.Methods Forty-eight SPF adult Sprague-Dawley rats (half male,half female),weighing 220-260 g,were divided into control group (C group,n =24) and sevoflurane group (S group,n =24) using a random number table method.Group C and group S inhaled air and 3％ sevoflurane,respectively,for 5 h.Eight rats in each group were sacrificed immediately after anesthesia,and the cerebral cortex was removed.Eight rats in each group were selected on days 1 and 7 after anesthesia and underwent Barnes maze test.The rats were then sacrificed,and the cerebral cortex was removed.The expression of ADRA1B and ADRA1D protein and mRNA in cerebral cortex tissues was detected by Western blot and fluorescent quantitative real-time polymerase chain reaction,respectively.Results Compared with group C,the number of entering incorrect holes was significantly increased at 1 and 7 days after anesthesia,the latency and total distance to enter the target hole were prolonged,and the expression of ADRA1B and ADRA1D protein and mRNA in cerebral cortex was down-regulated immediately after anesthesia and at 1 and 7 days after anesthesia in group S (P＜0.05).Conclusion The mechanism underlying sevoflurane-induced cognitive impairment may be related to the down-regulated expression of ADRA1B and ADRA1D in cerebral cortex of rats.

Role of α2A adrenergic receptors in dexmedetomidine-induced inhibition of TLR4/NF-κB signaling pathway activation during hypoxia-reoxygenation-caused injury to alveolar type Ⅱ epithelial cells / 中华麻醉学杂志

Objective To evaluate the role of α2A adrenergic receptor (α2AAR) in dexmedetomidine-induced inhibition of TLR4/NF-κB signaling pathway activation during hypoxia-reoxygenation (H/R)caused injury to alveolar type Ⅱ epithelial cells.Methods Type Ⅱ] alveolar epithelial cells of rats RLE6TN cells cultured in vitro were divided into 4 groups (n =6 each) using a random number table method:control group (group C),H/R injury group (group H/R),dexmedetomidine group (group D) and α2A AR small interfering RNA (siRNA) plus dexmedetomidine group (group α2AAR-siRNA+D).H/R was produced by exposing cells to 1％ O2-5％ CO2-94％ N2 for 24 h followed by 4-h reoxygenation.Cells were incubated for 1 h with dexmedetomidine at the final concentration of 1 nmol/L,and then H/R model was established in group D.In group α2AAR-siRNA+D,cells were transfected with 50 nmol/L α2AAR-siRNA,48 h later dexmedetomidine at the final concentration of 1 nmol/L was added,cells were incubated for 1 h,and then H/R model was established.The cell viability was measured using CCK-8 method,cell apoptosis rate was determined by flow cytometry,and the expression of TLR4 and NF-κB was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group H/R (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＞0.05).Compared with group H/R,the cell viability was significantly increased,the apoptosis rate was decreased,and the expression of TLR4 and NF-κB was down-regulated in group D (P＜0.05),and no significant change was found in the parameters mentioned above in group α2AAR-siRNA+D (P＞0.05).Compared with group D,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group α2AAR-siRNA+D (P＜0.05).Conclusion The mechanism by which dexmedetomidine inhibits TLR4/NF-κB signaling pathway activation may be related to activating α2AAR during H/R-caused injury to alveolar type Ⅱ epithelial cells.

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

Relationship between sevoflurane-induced cognitive decline and α1A norepinephrine receptor in cerebral cortex of rats / 中华麻醉学杂志

Objective To evaluate the relationship between sevoflurane-induced cognitive decline and α1A norepinephrine receptor (ADRA1A) in the cerebral cortex of rats.Methods Forty-eight cleangrade healthy adult Sprague-Dawley rats (24 male,24 female),weighing 220-260 g,aged 3-4 months old,were divided into 2 groups (n =24 each) using a random number table method:control group (group C) and sevoflurane group (S group).Group S inhaled 3％ sevoflurane for 5 h.Rats underwent the Barnes maze test on days 1 and 7 after anesthesia.Rats were sacrificed immediately after anesthesia and on days 1 and 7 after anesthesia,and the cerebral cortex was removed for determination of the expression of ADRA1A protein and mRNA (by Western blot or fluorescent quantitative real-time polymerase chain reaction).Results Compared with group C,the number of entering incorrect holes was significantly increased,and the latency of entering the target hole and the distance were prolonged,and the expression of ADRA1A protein and mRNA in cerebral cortex was down-regulated at each time point in group S (P＜0.05).Conclusion The mechanism of sevoflurane-induced cognitive decline is related to down-regulated expression of ADRA1A in the cerebral cortex of rats.

Effect of dexmedetomidine on visceral pain in rats: the role of a2 adrenergic receptors in locus coeruleus / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on visceral pain in rats and the role of α2 adrenergic receptors in locus coeruleus (LC).Methods Thirty-two healthy adult male SpragueDawley rats,weighing 250-300 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),visceral pain group (group VP),dexmedetomidine group (group DEX) and α2-adrenergic receptor antagonist atipamezole group (group AP).α2-adrenergic receptor antagonist atipamezole 522 μg/kg was intramuscularly injected in group AP,and the equal volume of normal saline was given instead in C,VP and DEX groups.At 10 min after intramuscular injection,dexmedetomidine 10 μg/kg was injected via the tail vein in DEX and AP groups,and the equal volume of normal saline was given instead in C and VP groups.VP,DEX and AP groups received intraperitoneal injection of 0.9％ acetic acid 10 ml/kg to make the visceral pain model at 15 min after injection via the tail vein.The cumulative visceral pain score was recorded within 60 min after acetic acid injection.The number of c-fos positive cells in LC was detected by immunohistochemistry,and the content of norepinephrine (NA) in the spinal cord were detected by enzyme-linked immunosorbent assay at 2 h after acetic acid injection.Results Compared with group C,the cumulative visceral pain scores,the number of c-fos positive cells in LC and content of NA in the spinal cord were significantly increased in VP,DEX and AP groups (P＜0.05).Compared with group VP,the cumulative visceral pain scores,the number of c-fos positive cells in LC and content of NA in the spinal cord were significantly decreased in DEX and AP groups (P＜0.05).Compared with group DEX,the cumulative visceral pain scores,the number of c-fos positive cells in LC and content of NA in the spinal cord were significantly increased in group AP (P＜0.05).Conclusion Dexmedetomidine can alleviate visceral pain in rats,and the mechanism is partially related to activating α2 adrenergic receptors in LC.

Effect of dexmedetomidine on long-term anxiety state after sevoflurane anesthesia in neonatal rats:the role of different central subtypes of α2 receptors / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on the long-term anxiety state after sevoflurane anesthesia in neonatal rats and the role of different central subtypes of α2 receptors.Methods A total of 216 clean-grade healthy male Sprague-Dawley rats,aged 4-6 days,weighing 8-15 g,were divided into 6 groups (n =36 each) using a random number table method:control group (group C),sevoflurane group (group S),dexmedetomidine + sevoflurane group (group D+S),dexmedetomidine + α2 receptor antagonist atipamezole + sevoflurane group (group D+A+S),dexmedetomidine + α2A receptor antagonist BRL44408 + sevoflurane group (group D+B+S),and dexmedetomidine + α2C receptor antagonist JP1302 + sevoflurane group (group D+J+S).Anesthesia was induced by inhaling 6％ sevoflurane for 3 min and maintained by inhaling 2.1％ sevoflurane for 6 h.At 30 min before anesthesia induction,dexmedetomidine 25 μg/kg was intraperitoneally injected in group D+S,dexmedetomidine 25 μg/kg and atipamezole 250 μg/kg were intraperitoneally injected in group D + A + S,dexmedetomidine and α2A receptor antagonist BRL44408 1.5 mg/kg were intraperitoneally injected in group D+B+S,and dexmedetomidine 25 μg/kg and α2C receptor antagonist JP1302 3 mg/kgwere intraperitoneally injected in group D+J+S.Twelve rats in each group were randomly selected and sacrificed after the end of anesthesia,blood samples were collected for blood gas analysis,and the serum corticosterone concentration was measured by enzyme-linked immunosorbent assay.The elevated plus maze was performed when the left rats in each group were 60 days old,and 12 rats were selected when the they were 80 days old to perform the restraint stress test.Results Compared with group C,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in S,D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in D+S and D+J+S groups (P＞0.05).Compared with group S,the percentage of time of staying at the open arm was significantly increased,the total motion distance was prolonged,and the serum corticosterone concentration was decreased after the end of anesthesia and during the restraint stress test in group D+S and group D+J+S (P＜0.05),and no significant change was found in the parameters mentioned above in group D+A+S and group D+B+S (P ＞0.05).Compared with group D+S,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in group D+J +S (P＞ 0.05).Conclusion Dexmedetomidine can reduce the long-term anxiety state after sevoflurane anesthesia in neonatal rats,and the mechanism may be related to activating central α2A receptors and improving hypothalamic-pituitary-adrenocortical axis hyperfunction.

Intoxicación por amitraz. Un reporte de caso / Amitrazpoisoning: case report

Resumen El amitraz es un compuesto insecticida utilizado a nivel mundial para el control de plagas, en especial en áreas rurales agrícolas y ganaderas. La intoxicación por amitraz es infrecuente en Colombia. Se presenta el caso de una paciente de 18 años de edad, quien ingresa al servicio de urgencias 3 horas después de la ingesta de Triatox® (amitraz) en cantidad desconocida. La mujer llega con depresión del estado de conciencia, dificultad respiratoria, hipotensión, bradicardia, miosis y acidosis metabólica compensada con alcalosis respiratoria, por lo que se le suministra tratamiento inicial con medidas de soporte vital en el servicio de urgencias, con posterior necesidad de traslado y soporte en la unidad de cuidados intensivos, siendo dada de alta de la misma unidad 24 horas después del ingreso. El caso pone en consideración la similitud clínica entre la intoxicación por amitraz y la debida a otros compuestos tóxicos más frecuentes como carbamatos, organofosforados y opioides, los cuales requieren un manejo distinto.

Abstract Amitraz is an insecticide compound used worldwide for controlling pests, especially in agricultural and livestock areas. However, amitraz poisoning in Colombia is rare. This article reports the case of an 18-year-old female patient who was admitted in the emergency service 3 hours after the intake of an unknown amount of Triatox® (amitraz). The patient presented with a depressed level of consciousness, respiratory distress, hypotension, bradycardia, myosis and metabolic acidosis compensated with respiratory alkalosis. Initial treatment was provided using life support measures in the emergency ward, and subsequent transfer and support in the intensive care unit. She was discharged 24 hours after admission. This case considers the clinical similarity between amitraz poisoning and poisoning caused by other more frequent toxic compounds such as carbamates, organophosphates and opioids, which require different management.

Role of α2 adrenergic receptors in dexmedetomidine-induced inhibition of lipid peroxidation during lung ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To evaluate the role of α2 adrenergic receptors in dexmedetomidine-induced inhibition of lipid peroxidation during lung ischemia-reperfusion (I/R) injury in rats.Methods Thirty-two isolated rat lungs in which the model of isolated lung perfusion was successfully established,were divided into 4 groups (n=8 each) using a random number table:control group (C group),I/R group,dexmedetomidine group (D group) and dexmedetomidine plus yohimbine group (DY group).The isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of reperfusion and ventilation to establish the model of isolated lung I/R injury.From the beginning of reperfusion,2.3 ng/ml dexmedetomidine was added to the perfusion fluid in D group,and 2.3 ng/ml dexmedetomidine and 0.4 μg/ml yohimbine (an α2 adrenergic receptor blocker) were added to the perfusion fluid in DY group.Lung specimens were obtained immediately after the end of reperfusion for determination of the wet/dry weight ratio (W/D ratio),superoxide dismutase (SOD) activity (by using modified pyrogallol autoxidation method) and malondialdehyde (MDA) content (by thiobarbituric acid method) and for examination of the pathological changes (using haematoxylin and eosin staining).Results Compared with C group,the W/D ratio and MDA content were significantly increased,and the SOD activity was decreased in I/R,D and DY groups (P＜0.05).Compared with I/R group,the W/D ratio and MDA content were significantly decreased,and the SOD activity was increased in D group (P＜0.05).Compared with DY group,the W/D ratio and MDA content were significantly decreased,and the SOD activity was increased in group D (P＜0.05).The pathological changes of lung tissues were significantly attenuated in D group as compared with I/R and DY groups.Conclusion The mechanism by which dexmedetomidine inhibits lipid peroxidation is related to activating α2 adrenergic receptors during lung I/R injury in rats.

β3-adrenoceptor activation promotes cholesterol efflux from foam cells by upregulating apoA-Ⅰ expression / 中华老年心脑血管病杂志

Objective To study the mechanism of β3 adrenoceptor (β3-AR) activation underlying cholesterol efflux by activating or inhibiting the β3-AR of HepG2 cells.Methods Cultured HepG2 cells were randomly divided into control group,β3-AR agonist group and β3-AR antagonist group.Serum levels of apoA-Ⅰ,apoA-Ⅱ,and β3-AR in supernatant fluid,and cholesterol,free cholesterol,cholesterol ester in HepG2 cells were measured by ELISA.Cholesterol efflux from macrophages was tested by 3H-labled cholesterol.Expressions of ABCA1 and LXRα mRNA and protein were detected by RT-PCR and Western blot respectively.Results The efflux rate of apoA-Ⅰ,cholesterol and cholesterol ester was significantly higher while the serum levels of cholesterol and cholesterol ester were significantly lower and the expression levels of ABCA1 and LXRα mRNA and protein were significantly higher in β3 AR agonist group than in control group.The serum levels of cholesterol and cholesterol ester were significantly higher while the efflux rate of cholesterol and cholesterol ester and the expression levels of ABCA1 and LXRα mRNA and protein were significantly lower in β3-AR antagonist groupt than in β3-AR agonist group (0.49±0.10 vs 1.24±0.02,0.85±0.05 vs 1.32±0.05,0.38±0.01 vs 1.45±0.20,0.08±0.01 vs 0.76±0.02,P＜0.01).Conclusion β3 AR promotes cholesterol efflux by upregulating the expression of apoA-Ⅰin HepG2 cells.

Effect of median nerve electrical stimulation on expression of α1-adrenergic receptor in prefrontal cortex of coma rats induced by traumatic brain injury / 重庆医学

Objective To investigate the wake-promoting action of median nerve electrical stimulation(MNES) in coma rats induced by traumatic brain injury(TBI) and its influence on the expression of α1-adrenergic receptor(α1 R) in the prefrontal contex (PFC).Methods Seventy-two healthy Sprague Dawley(SD) rats were randomly divided into the control group,sham-stimulated group(TBI),stimulated group (TBI+ MNES) and antagonist group(TBI+ OX1R antagonist +MNES).The control group had no any treatment.The TBI coma rat models were prepared in the other 3 groups.The sham stimulated group had no treatment.The antagonist group was injected with orexin receptor-l(OX1R) antagonist SB334867 into lateral ventricle,and both the antagonist group and stimulated group received MNES treatment.Then the behavior changes of rats in each group were observed and the α1 R expression level in PFC was detected by using the immunohistochemistry technique.Results Thirteen rats in the stimulated group and 8 rats in the antagonist group revived,while only 4 rats in the TBI group.The α1R levels from low to high were the blank control group,sham-stimulated group,antagonist group and stimulated group,showing the increasing trend,and the difference was statistically significant(P＜0.05).Conclusion MNES can improve the rat consciousness level after TBI coma,and its mechanism may be related with up-regulating the α1 R expression level in PFC area,moreover Orexin-A participates in this regulation process.

β3-adrenoceptor in heart and lungs of elderly heart failure rats / 中华老年心脑血管病杂志

Objective To study the β3-adrenoceptor (β3-AR) in heart and lungs of elderly heart failure (HF) rats.Methods Forty-eight elderly HF Wistar rats were included in this study.A HF model of rats was established by ligating the aorta.The rats were divided into sham operation group (n=24) and HF group (n=24).The rats in each group were further divided into 4 subgroups at weeks 5,7,9 and 11 after operation (6 in each group).The hemodynamics,pathology and expression of β3-AR mRNA and protein in heart and lungs were detected at weeks 5,7,9 and 11 respectively after operation.Results The heart rate,LVESP,and dp/dtmax were significantly lower in HF group than in sham operation group at weeks 9 and 11 after operation while the LVEDP was significantly higher in HF group than in sham operation group at weeks 5,7,9 and 11 after operation (P＜0.01).Pulmonary edema occurred at week 7 after operation and myocardial necrosis was detected at week 9 after operation.The expression level of β3-AR mRNA in lungs was significantly lower in HF group at weeks 5,7,9 and 11 than at week 2 after operation (P＜0.05).The expression level of β3-AR mRNA in heart was significantly higher in HF group than in sham operation group at weeks 9 and 11 after operation (1.21±0.26 vs 0.98±0.22,1.26±0.23 vs 1.05±0.24,P＜0.01).Conclusion The β3-AR mRNA expression is downregulated in the lungs and upregulated in the heart.

In vitro effects of propranolol and isoproterenol on the expression of beta-2 adrenergic receptor on infantile hemangioma endothelial cells / 中华皮肤科杂志

Objective To explore the role of beta-2 adrenergic receptor in the pathogenesis of infantile hemangioma.Methods In vitro cultured infantile hemangioma endothelial cells were divided into propranolol and isoproterenol groups.The propranolol groups were further classified into 5 groups to be treated with propranolol solutions at concentrations of 10,15,20 μg/ml,EGM-2 medium (blank control group 1),and EGM-2 medium containing 0.16％ DMSO (DMSO group) respectively,while the isoproterenol groups were classified into 4 groups to be treated with isoproterenol solutions at concentrations of 5,10,20 μg/ml and EGM-2 medium (blank control group 2) respectively.After 24-and 48-hour treatment,enzyme-linked immunosorbent assay (ELISA) was performed to measure the expression of beta-2 adrenergic receptor in cell culture supernatants in the above groups.Results After 24-hour treatment,15-μg/ml and 20-μg/ml propranolol groups showed significantly decreased expression of beta-2 adrenergic receptor compared with blank control group 1 and DMSO group (all P ＜ 0.05).After 48-hour treatment,all the propranolol groups showed significantly decreased expression of beta-2 adrenergic receptor compared with the blank control group 1 (all P ＜ 0.05).However,the expression of beta-2 adrenergic receptor was significantly higher in the 10-and 20-μg/ml isoproterenol groups than in the blank control group 2 after 24-hour treatment (all P ＜ 0.05),and higher in the 20-μg/ml isoproterenol group than in the blank control group 2 after 48-hour treatment (P ＜ 0.05).Conclusion Propranolol can down-regulate the expression of beta-2 adrenergic receptor on the surface of vascular endothelial cells,while isoproterenol can up-regulate its expression.

Relationship Between β2-Adrenergic Receptor Gln27Glu Gene Polymorphism and Essential Hypertension Occurrence in Tibetan Population Living at High Altitude Area / 中国循环杂志

Objective: To investigate β2 adrenergic receptor (β2-AR) gene polymorphism, Arg16Gly, Gln27Glu and essential hypertension (EH) occurrence in Tibetan population living at high altitude area. Methods: Our research included in 2 groups: EH group, n=385 patients and Control group,n=297 normal healthy subjects. β2-AR polymorphisms of Arg16Gly and Gln27Glu were detected by Snapshot mini-sequencing technique and their frequencies were compared between 2 groups and male, female genders. Results: The genotype and allele frequency distributions of Arg16Gly and Gln27G1u were similar between 2 groups, P>0.05; there were no signiifcant differences between male and female genders,P>0.05. Conclusion: No obvious relationship was found between β2-AR gene polymorphism (Arg16Gly, Gln27Glu) and EH occurrence in Tibetan population living at high altitude area.

Nicergoline improves the depressive behavior of vascular depression in rats by regulating monoamine neurotransmitter receptors expression in hippocampal CA1 region and serum apolipoprotein E4 level / 国际脑血管病杂志

Objective To investigate the effects of nicergoline on expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), D2 dopamine receptor (D2DR),α2A adrenaline receptor (α2AAR) in the hippocampal CA1 region and the serum level of apolipoprotein E4 (ApoE4) in a rat model of vascular depression (VD) . Methods Forty-eight male Sprague-Daw ley rats w ere randomly al ocated into a normal control group, a model group, fluoxetine group, a low-dose nicergoline group, a medium-dose nicergoline group, and a nicergoline high-dose group ( n=8 in each group). A rat model of VD w as induced by the ligation of bilateral common carotid arteries combined w ith chronic unpredictable mild stress (CUMS) plus single housing. The rats did not conduct CUMS or single housing in the normal control group, and the rats in the model group conducted CUMS and single housing. The rats in the fluoxetine group w ere given fluoxetine 1.3 mg/(kg· d) for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The rats in the low -, medium-and high-dose nicergoline groups w ere given nicergoline 0.9, 1.9 and 3.8 mg/(kg· d), respectively for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The normal control group and the model group w ere given equal volume of distil ed w ater for gastric lavage, once a day for 3 w eeks. Depression-like behavior w as evaluated using sucrose solution consumption and open-field test. Immunohistochemical staining and Western blot were used to detect the expressions of 5-HT1AR, D2DR, andα2AAR in the hippocampal CA1 region. Enzyme linked immunosorbent assay w as used to detect serum ApoE4 level. Results Before CUMS, the scores of horizontal and vertical movement and sucrose solution consumption in the model group, the fluoxetine group and each nicergoline group w ere decreased significantly compared w ith the normal control group (al P<0.01);w hile at 21 days after CUMS, those in the fluoxetine group and the nicergoline medium-and high-dose groups w ere significantly higher than those in the model group (al P<0.05). There w ere no significant differences betw een the fluoxetine group and each nicergoline group. The expression levels of 5-HT1A R, D2DR, α2A AR, and the serum ApoE4 in the model group, the fluoxetine group, and each nicergoline group w ere significantly higher than those in the normal control group. Those of the fluoxetine group and the nicergoline medium -and high-dose groups were significantly lower than the model group (al P<0.01), while there were no significant differences betw een the fluoxetine group and each nicergoline group. Conclusions Nicergoline can improve the depression-like behavior in VD rats. Its mechanism may be associated w ith the dow nregulation of 5-HT1AR, D2DR, α2AAR expressions and serum ApoE4 level.

Possible molecular mechanism of β2 adrenergic signaling pathway in regulation of inflammation after stroke / 国际脑血管病杂志

Infection is one of the common complications of stroke. It can seriously affect the prognosis of patients. Poststroke infection is closely associated with immune system imbalance, while the excessive activation of sympathetic nerve is an important factor of the occurrence of immunosuppression after stroke. The sympathetic nerve regulates immune cels primarily via β2 adrenergic receptors on the surface of the immune cels. There is evidence to show that β2 adrenergic receptor mediated immune function enhances rather than inhibits under certain conditions, but its specific molecular mechanism is unclear. This article reviews the molecular mechanisms of β2 adrenergic signaling pathway in regulation of inflammation after stroke.

Overexpression of β3-adrenoreceptor aggravates cardiac hypertrophy / 实用医学杂志

Objective To investigate the effect of β3-adrenoreceptor (β3-AR)overexpression on cardiac hypertrophy. Method Sprague-Dawley rat neonatal ventricular cardiomyocytes (NRVMs) were isolated and cul-tured in vitro.The infection of lentiviruswas examined after cardiomyocytes were infected with lentivirus at differ-ent multiplicity of infection (MOI) of 20、50、80 and 100. Fluorescence microscopy was used to observe the ex-pression of GFP and to confirm the best MOI for lentivirus infection. Following the enforced expression of β3-AR by lentivirus, 2uM norepinephrine (NE) was used to treatment the infected cardiomyocytes for 48h. Expressions of β3-AR、c-myc and c-fos protein in cardiomyocytes were detected by Western Blot. Results The results of fluorescence microscopy indicated that the best MOI was 50. The protein level of β3-AR was significantly in-creased in β3-AR overexpression group compared with the control group and the NE treatment group (P < 0.05). Following the treatment of NE , the expressions of c-myc and c-fos were also significantly increased in β3-AR overexpression group compared with the control group (P < 0.05). Conclusion Over-expression of β3-AR can aggravate cardiomyocyte hypertrophy.