Adenylate cyclase activates the cAMP signalling pathway to enhance platelet-rich plasma-treated Achilles tendon disease,a theoretical bioinformatics-based study

The effectiveness of platelet-rich plasma(PRP)for the treatment of Achilles tendon disorders still needs to be evaluated through a series of prospective studies,but genomic analysis can reveal the existence of complementary PRP treatment options.Based on the 96 platelet activation-related genes in the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,we performed Gene Ontology functional enrichment analysis and KEGG enrichment analysis,pathway correlation analysis,and enrichment mapping to determine the enrichment results of the gene set enrichment analysis and found that the cAMP signalling pathway may be the key to enhancing the effectiveness of PRP treatment.The cAMP signalling pathway interacts with the Rap1 signalling pathway and cGMPPKG signalling pathway to mediate the entire pathophy-siological process of Achilles tendon disease.Moreover,ADCY1-9 may be the key to the activation of the cAMP signalling network.Further based on the data in the Gene Expression Omnibus database,it was found that ADCY4 and ADCY7 may be the players that play a major role,associated with the STAT4-ADCY4-LAMA5 axis and the GRbeta-ADCY7-SEMA3C axis,which is expected to be a complementary target for enhancing the efficacy of PRP in the treatment of Achilles tendon disease.

Characterization of two halophilic adenylate cyclases from Thermobifida halotolerans and Haloactinopolyspora alba

Adenylate cyclase(AC)is the key enzyme that catalyzes the formation of cAMP from ATP.In this study,we discovered two novel class Ⅲ ACs with a halophilic property from Thermobifida halotolerans DSM 44931(ThAC)and Haloactinopolyspora alba DSM 45211(HaAC),respectively.The recombinant ThAC and HaAC were expressed in Escherichia coli with molecular weights of 36.1 and 36.0 kDa respectively.The presence of 2500 and 2200 mmol
L^(-1)1 NaCl significantly enhanced the enzyme activities of ThAC and HaAC,with 22-fold and 7.4-fold higher activities compared to those without NaCl,respectively.Several divalent metal ions were found to activate the recombinant ACs to different extents,and the optimal metal ion was Mg^(2+)for both ThAC and HaAC with concentrations of 80 mmol·L^(-1) and 40 mmol·L^(-1) respectively.Purified ThAC and HaAC had the optimal specific activities((4.59±0.35)×10^(4) and(7.76±0.52)×10^(4) U·mg^(-1))and catalytic efficiency(4.47 and 5.30 L·mmol^(-1)·s^(-1))at 45
℃ and 40
℃ respectively,while the optimum pH of both two recombinant ACs was 10.0.This is the first report of the halophilic Class III ACs,which could make new contributions to explore and study ACs for further associated investigations.

Effect of Fish Oil on (-Adrenoceptors and the Activity of Adenylate Cyclase on Myocardial Membrane in Rats

Effects of fish oil on β-adrenoceptors as well as the activity of adenylate cyclase (AC) on rat myocardial membrane were investigated.Supplementation with fish oil had no significant effect on basal activity of AC on myocardial membrane whereas it could markedly inhibit the AC activity stimulated by isoproterenol (ISO). Radioligand binding assays showed that supplementation with fish oil had no effect on Bmax and Kd, compared with saline control. However, supplementation with sheep oil could markedly reduce both the Kd and Bmax, compared with saline control. And the Kd of sheep oil group was greatly decreased than that of fish oil group. The results suggested that supplementation with fish oil mainly affected the activation of AC, not β-adrenoceptor itself.

Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide （YLSPS; 150, 300 and 600 mg/kg） for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS （300 and 600 mg/kg）, monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).

Cloning,tissue distribution and effects of fasting on pituitary adenylate cyclase-activating polypeptide in largemouth bass

Pituitary adenylate cyclase activating polypeptide （PACAP） has a wide range of biological functions. We cloned the full-length cDNAs encoding PACAP and PACAP-related peptide （PRP） from the brain of largemouth bass （Micropterus salmoides） and used real-time quantitative PCR to detect PRP- PACAP mRNA expression. The PRP-PACAP cDNA has two variants expressed via alternative splicing： a long form, which encodes both PRP and PACAP, and a short form, which encodes only PACAR Sequence analysis results are consistent with a higher conservation of PACAP than PRP peptide sequences. The expression of PACAP-Iong and PACAP-short transcripts was highest in the forebrain, followed by the medulla, midbrain, pituitary, stomach, cerebellum, intestine, and kidney; however, these transcripts were either absent or were weakly expressed in the muscle, spleen, gill, heart, fatty tissue, and liver. The level of PACAP-short transcript expression was significantly higher than expression of the long transcript in the forebrain, cerebella, pituitary and intestine, but lower than that of the long transcript in the stomach. PA CAP- long and PACAP-short transcripts were first detected at the blastula stage of embryogenesis, and the level of expression increased markedly between the muscular contraction stage and 3 d post hatch （dph）. The expression of PACAP-long and PACAP-short transcripts decreased significantly in the brain following 4 d fasting compared with the control diet group. The down-regulation effect was enhanced as fasting continued. Conversely, expression levels increased significantly after 3 d of re-feeding. Our results suggest that PRP- PA CAP acts as an important factor in appetite regulation in largemouth bass.

Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington＇s disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination（grip strength, beam crossing task, locomotor activity）, resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington＇s disease-like neurodegeneration.

Effects of pituitary adenylate cyclase activating polypeptide on CD4^+/CD8^+T cell levels after traumatic brain injury in a rat model

BACKGROUND： The effect of pituitary adenylate cyclase activating polypeptide （PACAP） during traumatic brain injury （TBI） and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS： Male Sprague Dawley rats were randomly divided into 3 treatment groups （n=6, each）： sham-operated, vehicle （normal saline）＋TBI, and PACAP＋TBI. Normal saline or PACAP （1 μg/5 μL） was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4＋ and CD8＋ T cells in blood and the spleen were detected via flow cytometry.RESULTS： In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4＋ CD8＋ lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBl＋vehicle, and CD4- CD8＋ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4＋, and decreased CD8＋, T lymphocytes in blood and the spleen.CONCLUSION： Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.

Changes of the binding capacity of insulin receptors and activities of adenylate cyclase in hepatocytes after scalding in rats

In order to investigate the effects of transmembranous conduction of signals on insulin resistance after scalding,the changes of the binding capacity of insulin receptors in the cell membrane of hepatocytes and the activities of adenylate cyclase were observed in rats after they were inflicted with 30% TBSA full thickness scalding. It was found that the maximum binding capacity of insulin receptors was significantly decreased after scalding but the average affinity increased. The sensitivity of insulin inhibition on the activity of adenylate cyclase was significantly reduced but there was no apparent difference of the maximum inhibition activity. These findings suggest that the impairment of transmembranous conduction of insulin signals across the cell membrane of hepatocytes after scalding can result in abnormal metabolism of glucose and consequently insulin resistance.

Effect of Cardiopulmonary Bypass on Beta Adrenergic Receptor Adenylate Cyclase System on Surfaces of Peripheral Lymphocytes

Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces, which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.

Efficient production of cyclic adenosine monophosphate from adenosine triphosphate by the N-terminal half of adenylate cyclase from Escherichia coli

In this study,we aimed at developing an efficient biocatalytic process for bio-production of cyclic adenosine monophosphate(c AMP)from adenosine triphosphate(ATP).First,adenylate cyclase from Escherichia coli MG1655(EAC)and Bordetella Pertussis(BAC)were expressed in E.coli BL21(DE3)and comparatively analyzed for their activities.As a result,EAC from E.coli MG1655 exhibited a higher activity.However,amount of EAC were obtained in an insoluble form.Therefore,we expressed the first 446 amino acids of EAC(EAC446)to avoid the inclusion body.The effects of induction temperature,incubation time,and incubation p H were further evaluated to improve the expression of EAC446.Subsequently,the reaction process for the production of c AMP with ATP as a starting material was investigated.As none of c AMP was detected in the whole-cell based biocatalytic process,the reaction catalyzed by the crude enzyme was determined for c AMP production.What's more,the reaction temperature,reaction p H,metal ion additives and substrate concentration was optimized,and the maximum c AMP production of 18.45 g·L^-1was achieved with a yield of 95.4%after bioconversion of 6 h.

No association between a polymorphism of the adenylate cyclase type IX gene and major depressive disorder in the Chinese Han population

Previous studies have demonstrated that a missense single-nucleotide polymorphism variant （2316A〉G;rs2230739）of the adenylate cyclase type IX gene was associated with bipolar disorder and affective disorder.We determined genotype and allele frequencies using a ligase detection reaction method in 315 patients with major depressive disorder and 278 unrelated, sex-matched healthy control subjects.We did not detect any statistically significant differences in genotype and allele frequencies between patients and healthy control subjects.Furthermore,we found no significant difference between genders in major depressive disorder,nor between patients and controls in the same gender.These results suggest that 2316A〉G（rs2230739）may not be a risk factor for increasing susceptibility to major depressive disorder in the Chinese Han population.

扶阳温灸膏对阳虚体质膝骨关节炎患者关节液PACAP和血清IL-1β、MMP-3的影响

目的:研究扶阳温灸膏对阳虚体质膝骨关节炎(knee osteoarthritis,KOA)患者关节液垂体腺苷酸环化酶激活多肽(pituitary adenylyl cyclase activating polypeptide,PACAP)和血清白细胞介素-1β(interleukin-1β,IL-1β)、基质金属蛋白酶3(matrix metalloproteinase-3,MMP-3)表达的影响。方法:选择2021年1—12月于广东省第二中医院接受治疗的120例阳虚体质KOA患者,并采用随机数字表法的分组方法,把患者分为对照组和观察组,各60例。对照组给予玻璃酸钠注射液治疗,观察组行扶阳温灸膏治疗。比较两组临床总有效率、PACAP、IL-1β、MMP-3、视觉模拟评分法(VAS)评分、Lysholm膝关节评分、简明健康状况调查量表(SF-36)评分。结果:观察组临床治疗总有效率较对照组更高(P<0.05)。治疗4、8周后,两组PACAP水平均较治疗前升高,且治疗8周后两组PACAP水平均较治疗4周后更高,观察组高于对照组(P<0.05);两组IL-1β、MMP-3水平、VAS评分均较治疗前下降,且治疗8周后两组IL-1β、MMP-3水平、VAS评分均较治疗4周后更低,观察组均低于对照组,差异均有统计学意义(P<0.05)。治疗4、8周后,两组Lysholm膝关节评分均较治疗前升高,且治疗8周后两组Lysholm膝关节评分均高于治疗4周后,且观察组均较对照组更高,差异均有统计学意义(P<0.05)。治疗4、8周后,两组SF-36评分均较治疗前增加,且治疗8周后两组患者SF-36评分均较治疗4周后更高,观察组高于对照组,差异均有统计学意义(P<0.05)。结论:扶阳温灸膏治疗阳虚体质KOA效果显著,可调控患者关节液PACAP和血清IL-1β、MMP-3水平表达并改善膝关节疼痛症状与功能,可有效提高生活质量水平。

PACAP作用于神经胶质瘤的研究进展

垂体腺苷酸环化酶激活多肽(PACAP)是一种存在于体内的神经肽,参与包括cAMP/PKA/CREB、PI3K/Akt等信号通路的调节。神经胶质瘤是发生于中枢神经系统的原发性肿瘤,PACAP在调节部分胶质瘤细胞的增殖、侵袭和迁移过程中发挥重要作用。该文就PACAP作用于胶质瘤细胞的相关机制做一综述。

电针颈夹脊穴对神经根型颈椎病神经病理性疼痛模型大鼠脊髓背角CX3CL1、AC3、CGRP和SP物质表达的影响

目的观察电针颈夹脊穴对神经根型颈椎病(cervical spondylotic radiculopathy,CSR)神经病理性疼痛大鼠脊髓背角CX3C趋化因子配体1(C-X3-C motif chemokine ligand 1,CX3CL1)、腺苷酸环化酶3(adenylate cyclase 3,AC3)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)和P物质(substance P,SP)表达的影响,探讨电针颈夹脊穴治疗CSR引起的神经病理性疼痛的相关镇痛机制。方法48只雄性SD大鼠随机分为空白组、假手术组、模型组和电针组,每组12只。电针组给予电针双侧C6、C7夹脊穴,模型组和假手术组在电针组干预同时间点进行绑缚处置。观察大鼠在术前第1天、术后第14天、术后第28天患侧前足热刺激缩足反射潜伏期(paw withdrawal thermal latency,PWTL)的变化,采用Western blot法和Real time PCR法检测患侧脊髓背角CX3CL1蛋白和基因的表达,采用免疫荧光法检测患侧脊髓背角AC3、CGRP和SP的表达。结果各时间点与空白组比较,假手术组患侧前足PWTL差异均无统计学意义(P>0.05);术后第14天,与假手术组比较,模型组和电针组大鼠患侧前足PWTL均减少(P<0.01);术后第28天,与模型组大鼠比较,电针组大鼠患侧前足PWTL升高(P<0.01);电针组大鼠术后第28天患侧前足PWTL较术后第14天升高(P<0.01)。与空白组比较,假手术组大鼠患侧脊髓背角CX3CL1、AC3、CGRP、SP蛋白和CX3CL1基因的表达差异均无统计学意义(P>0.05);与假手术组比较,模型组大鼠患侧脊髓背角CX3CL1、AC3、CGRP、SP蛋白和CX3CL1基因的表达均明显升高(P<0.01);与模型组相比,电针组大鼠患侧脊髓背角CX3CL1、AC3、CGRP、SP蛋白和CX3CL1基因的表达均明显降低(P<0.05)。结论电针颈夹脊穴治能够改善CSR神经病理性疼痛模型大鼠的热痛觉过敏,并通过抑制脊髓背角初级感觉神经元的CX3CL1、AC3、CGRP和SP合成表达,减轻了神经炎性反应,降低脊髓背角初级感觉神经元的兴奋性,从而阻碍神经中枢的敏化。

岛叶通过GluA1受体和腺苷酸环化酶1参与调控大鼠头痛及相关焦虑行为

目的:通过大鼠模型明确岛叶是否参与偏头痛发病并探索其机制。方法:连续硬膜外注射炎症汤建立慢性偏头痛(chronic migraine,CM)大鼠模型。von Frey纤维丝评估眶周机械阈值。通过旷场和高架十字迷宫实验观察动物焦虑行为。使用免疫印迹实验检测岛叶α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,AMPA)受体亚基1-Glu A1受体及腺苷酸环化酶1(adenylate cyclase 1,AC1)的表达。通过双侧岛叶注射AC1抑制剂探索可能的机制。结果:连续炎症汤刺激硬脑膜可诱导大鼠产生偏头痛样头痛及焦虑行为。与对照组相比,CM组岛叶的c-Fos、Glu A1及其磷酸化(p-Glu A1-S845)和AC1的表达显著增加。岛叶注射AC1抑制剂可缓解大鼠的痛觉过敏和焦虑行为,降低岛叶AC1和Glu A1表达量及p-Glu A1-S845水平。结论:岛叶可能通过Glu A1及AC1参与调控大鼠偏头痛样头痛及焦虑行为。

PACAP对培养大鼠海马神经元损伤的保护作用

目的 观察垂体腺苷酸环化酶激活肽 (PACAP)对谷氨酸和葡萄糖缺乏所致海马神经元损伤的保护作用。方法 取新生SD大鼠海马 ,采用B2 7无血清培养基培养神经元 ,MTT法测定神经元存活率 ;分别给予谷氨酸、NMDA或葡萄糖缺乏处理 ,造成原代培养的海马神经元损伤。结果 谷氨酸、NMDA呈剂量依赖性降低海马神经元的存活率 ,葡萄糖缺乏也能明显降低海马神经元的存活率 ,而预先给予PACAP能明显增加海马神经元的存活率。结论 PACAP能保护原代培养的海马神经元 ,减轻谷氨酸和葡萄糖缺乏引起的损伤。

PACAP对家兔实验性冠状动脉粥样硬化心脏形态重塑的干预作用

目的:研究垂体腺苷酸环化酶激活肽(PACAP)对冠状动脉粥样硬化(AS)形成过程中家兔心脏重塑的干预。方法:雄性新西兰家兔60只,随机等分为正常对照组(C组)、AS模型组(A组)及PACAP干预组(P组)。于实验第4、8、12周末每组随机处死动物5-6只,定位取带有冠脉主干及分支的心脏组织制作石蜡切片,分别行HE、van Gieson染色,在光镜下进行定性观察和/或定量分析。结果:(1)C组心脏组织无病变。A组及P组冠状动脉的主干和小分支内均有斑块形成,心肌间胶原成分增多;但P组冠脉小分支内病变及相应部位胶原沉积较同期A组的轻。(2)A组冠状微动脉重塑指数增大,12周末时(2.58±1.54)显著高于同期C组(1.34±0.58)和P组(1.39±0.48)(P<0.05);心肌细胞最大横径缩小,8周末时(13.85μm±2.27μm)已显著小于同期C组(14.68μm±2.40μm)(P<0.05),12周末时显著小于同期C组和P组。(3)P组的上述相应参数与C组无明显差异(P>0.05)。结论:PACAP可抑制家兔冠状AS形成过程中存在的冠状动脉及心肌形态不良改变。

基于垂体腺苷酸环化酶激活多肽在帕金森动物模型中的神经保护作用及机制探索

目的 探讨垂体腺苷酸环化酶激活多肽(PACAP)在帕金森病(PD)动物模型中的神经保护作用及机制。方法SD大鼠设置假手术组(Sham组)、PD组(帕金森造模组)、PD+PACAP_低浓度组(造模+按体重5μg/kg予PACAP鼻腔给药)、PD+PACAP_中浓度组(造模+按体重10μg/kg予PACAP鼻腔给药)、PD+PACAP_高浓度组(造模+按体重20μg/kg予PACAP鼻腔给药) 5组,最终每组纳入10只。四个PD组将脂多糖溶液注射至SD大鼠黑质中建立PD模型,假手术组同法操作但注射生理盐水。通过转棒法检测大鼠行为学表现;ELISA法检测黑质谷氨酸浓度(Glu)和α-突触核蛋白(α-syn)水平,WB法检测黑质α-syn及核因子激活的B细胞的κ-轻链(NF-κB)、核因子κB抑制蛋白α (IκBα)的表达水平;实时荧光定量聚合酶链式反应法(qPCR)检测大鼠黑质炎症因子肿瘤坏死因子α (TNF-α)、白细胞介素-1β (IL-1β)、白细胞介素-6IL-6的mRNA表达水平;WB法和免疫荧光法检测核转录因子胶质纤维酸性蛋白(GFAP)水平来观察星形胶质细胞的活化水平,TUNEL法检测黑质神经元的凋亡情况。结果 (1)行为学结果显示,在转棒实验中,与Sham组比较,PD组潜伏期缩短,掉落次数增加(37.20±5.27次/min);与PD组比较,PACAP组潜伏期延长,掉落次数减少(14.50±2.32次/min),PACAP治疗组的潜伏期和掉落次数随着PACAP浓度的增加而潜伏期可以更长,掉落次数可以更少(P<0.001)。(2)星形胶质细胞激活相关指标显示,PD组GFAP表达水平和黑质神经元的凋亡数量较Sham组显著升高;PACAP治疗组上述指标随着PACAP的浓度增加而显著减低(P<0.01)。(3)黑质神经炎症指标显示,与Sham组比较,PD组NF-κB含量及TNF-α、IL-1β、IL-6的mRNA显著升高,IκBα含量显著降低;PACAP治疗组NF-κB含量及TNF-α、IL-1β、IL-6的mRNA随着PACAP的浓度增加而减低,IκBα含量随着PACAP的浓度增加而升高(P<0.01)。(4) PD疾病特征指标显示,PD组谷氨酸和α-syn含量均较Sham组显著升高,3个PACAP组的上述指标较PD组显著降低;PACAP治疗组的上述指标随着PACAP的浓度增加而递减(P<0.01),以PD+PACAP_高浓度组效果最为明显。结论 PACAP在PD模型中具有神经保护作用,其机制可能为通过抑制星形胶质细胞激活来减轻神经炎症的发生。

PACAP受体激活对抗Aβ_(25-35)致神经元凋亡作用的观察

目的和方法 :本研究采用体外原代培养新生大鼠海马神经元的方法探讨了垂体腺苷环化酶激活多肽(PACAP)对抗淀粉样蛋白 (Aβ2 5-3 5)致凋亡的作用机理。结果 :2 5 μmol/L的Aβ蛋白处理神经元 5d即有明显的凋亡特征出现。PACAP2 7(P2 7)在正常情况下对海马神经元无明显营养作用 ,但当Aβ导致神经元凋亡时P2 7有显著的保护作用 ,可以提高神经元的活性 ,减少细胞凋亡数目 ,降低基因组小片段DNA含量。PACAP受体拮抗剂PACAP6 - 2 7(P6 - 2 7)可以逆转P2 7的保护作用。结论 :研究结果说明PACAP通过受体激活参与对抗Aβ的神经毒性效应。