Attenuation of nicotine-evoked Ca²⁺influx by antibody to the nicotinic acetylcholine receptor <i>α</i>3 subunits in human embryonic kidney cells

Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.

Effect of differential rearing environments on nicotine-stimulated locomotor activity and nicotinic acetylcholine receptor subtypes

OBJECTIVE Individuals vary in sensitivity to the behavioral effects of nicotine,resulting in differences in their vulnerability to addiction.The role of rearing environment in determining individual sensitivity to nicotine is unclear.The neuropharmacological mechanisms mediating the effect of rearing environment on the actions of nicotine are also understood.Thus,the contribution of rearing environment in determining the sensitivity to the locomotor effects of nicotine and regulating α4β2*-and α7-nicotinic acetylcholine(n ACh) receptor expressionwas determined in rats reared in isolated(IC) or enriched(EC) conditions.METHODS To measure locomotor activity,adolescent rats(postnatal day 21-51)were injected with saline(1 mL·kg^(-1)) or nicotine(0.3 mg·kg^(-1)) subcutaneously,then placed in chamberswhere ambulatory activity was monitored for 30-min by computer for 14 daily sessions.α4β2*-andα7-n ACh receptor expression in the mesolimbic dopamine pathway was determined by quantitative autoradiography of [125 I]-epibatidine and [125 I]-bungarotoxinbinding,respectively,in 16 μmol·L^(-1) coronal sections.Values for receptor expression in fmol are ±s of 8 brains and compared by two-tailed,unpaired t-test with P<0.05 considered significant.RESULTS EC-rats are similarly sensitive as IC-rats to the locomotor effects of nicotine.[125 I]-epibatidine binding in the ventral tegmental area of EC-rats was reduced(2.8±0.3 fmo L) compared to IC-rats(4.0±0.4 fmo L);there was no difference in the nucleus accumbens.There was no difference between EC-and IC-rats in α7-n ACh receptor expression in the mesolimbic dopamine pathway.CONCLUSION Rearing environment differentially regulates n ACh receptor subtypes in EC and IC rats.These data suggest regulation of n ACh receptors by environmental factors may be a mechanism for the protective effect of enrichment against altered sensitivity to nicotine in genetically vulnerable individuals.The characterization of these mechanisms will aid in development of novel pharmacological tools mimicking the protection afforded by environmental enrichment in nicotine-sensitive individuals.

Vagus nerve stimulation protects against cerebral injury after cardiopulmonary resuscitation by inhibiting inflammation through the TLR4/NF-κB and α7nAChR/JAK2 signaling pathways

BACKGROUND: Our previous research proved that vagus nerve stimulation(VNS) improved the neurological outcome after cardiopulmonary resuscitation(CPR) by activating α7 nicotinic acetylcholine receptor(α7nAChR) in a rat model, but the underlying mechanism of VNS in neuroprotection after CPR remains unclear.METHODS: In vivo, we established a mouse model of cardiac arrest(CA)/CPR to observe the survival rate, and the changes in inflammatory factors and brain tissue after VNS treatment. In vitro, we examined the effects of α7nAChR agonist on ischemia/reperfusion(I/R)-induced inflammation in BV2 cells under oxygen-glucose deprivation/reoxygenation(OGD/R) conditions. We observed the changes in cell survival rate, the levels of inflammatory factors, and the expressions of α7nAChR/Janus kinase 2(JAK2) and toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB).RESULTS: In vivo, VNS preconditioning enhanced functional recovery, improved the survival rate, and reduced hippocampal CA1 cell damage, and the levels of inflammatory mediators after CA/CPR. The application of α7nAChR agonists provided similar effects against cerebral injury after the return of spontaneous circulation(ROSC), while α7nAChR antagonists reversed these neuroprotective impacts. The in vitro results mostly matched the findings in vivo. OGD/R increased the expression of tumor necrosis factor-alpha(TNF-α), TLR4 and NF-κB p65. When nicotine was added to the OGD/R model, the expression of TLR4, NF-κB p65, and TNF-α decreased, while the phosphorylation of JAK2 increased, which was prevented by preconditioning with α7nAChR or JAK2 antagonists.CONCLUSION: The neuroprotective effect of VNS correlated with the activation of α7nAChR. VNS may alleviate cerebral IR injury by inhibiting TLR4/NF-κB and activating the α7nAChR/JAK2 signaling pathway.

Association of nicotinic acetylcholine receptor subunit alpha-4 polymorphisms with smoking behaviors in Chinese male smokers

Background it has been reported that the nicotinic acetylcholine receptor subunit a4 gene （CHRNA4） might be associated with smoking behaviors in the previous studies. Up to now, there are few reports on the relationship between CHRNA4 and smoking initiation, in this study, we tried to explore the role of two polymorphisms in CHRNA4 （rs1044396 and rs1044397） in smoking initiation and nicotine dependence in Chinese male smokers. Methods Nine hundred and sixty-six Chinese male lifetime nonsmokers and smokers were assessed by the Fagerstr6m test for nicotine dependence （FTND）, smoking quantity （SQ） and the heaviness of smoking index （HSI）.

Antinociceptive effects of novel epibatidine analogs through activation of α4β2 nicotinic receptors

The study of α4β2 nicotinic receptors has provided new indications in the treatment of pain. Efforts have been made to explore new α4β2 nicotinic receptor agonists, including TC-2559, as antinociceptive drugs. In this study, we discovered a set of novel epibatidine analogs with strong binding affinities to the α4β2 nicotinic receptors. Among these compounds, C-159, C-163, and C-9515 attenuated formalin-induced nociceptive responses in mice; C-9515 caused the most potent analgesic effect, which was blocked by mecamylamine, a non-selective nicotinic receptor antagonist. Furthermore, C-9515 potently inhibited chronic constriction injury(CCI)-induced neuropathic pain in rats, which was sensitive to DHβE, a selective α4β2 subtype antagonist,indicating that its analgesic effect was mediated by the activation of the α4β2 nicotinic receptors. In conclusion, the epibatidine analog C-9515 was found to be a potent α4β2 nicotinic receptor agonist with potent analgesic function, which demonstrated potential for the further exploration of its druggability.

精神分裂症伴发2型糖尿病与烟碱型乙酰胆碱受体基因多态性关联研究

目的在中国汉族精神分裂症患者中探讨烟碱型乙酰胆碱受体基因多态性与2型糖尿病共病的关联。方法采用Taq Man荧光探针基因分型技术对346例伴发2型糖尿病的中国汉族精神分裂症患者和360例不伴糖尿病的精神分裂症患者的α3、α4、α7、α5烟碱型乙酰胆碱受体(neuronal nicotinic acetylcholine receptor,n Ach R)基因即CHRNA3(rs1317286)、CHRNA4(rs1044396)、CHRNA7(rs6494212)及CHRNA5(rs16969968、rs684513)多态位点进行基因分型,比较等位基因频率和基因型频率,并进一步进行基因-基因交互作用分析。结果单位点分析显示男性患者rs6494212位点的等位基因分布和基因型分布在两组间差异均有统计学意义(P<0.05);rs1317286、rs1044396、rs16969968、rs684513位点的基因型分布和等位基因分布均无明显差异(P均>0.05)。CHRNA5基因的两个单核苷酸多态位点(single nucleotide polymorphisms,SNPs)组成的单体型与两组疾病共病关联无统计学意义(P>0.05)。进一步基因交互作用分析显示rs131726、rs1044396、rs6494212及rs684513这4个位点的联合作用模式可能与两组疾病共病相关(P=0.002)。结论 CHRNA7(rs6494212)可能是中国汉族男性精神分裂症患者患2型糖尿病的易感基因。rs1317286、rs1044396、rs6494212及rs684513位点的联合作用可能与精神分裂症共病2型糖尿病相关。

烟碱通过α7 nAChR-JAK2通路抑制BV2小胶质细胞炎症因子的释放

神经炎症是包括帕金森病(Parkinson’s disease,PD)等的神经退行性疾病重要的发病机制之一。因此,抑制神经炎症应该是改善神经退行性疾病的有效途径。烟碱等烟碱型乙酰胆碱受体(nicotinic acetylcholine receptors,nAChR)激动剂对PD的干预有积极作用,但是其具体的机制尚不明确。本文主要通过细胞来研究烟碱在神经炎症模型中调节小胶质细胞炎症因子分泌及其在神经元的保护中发挥的作用,并进一步探讨烟碱发挥抗炎作用的分子机制。为此,用脂多糖(LPS)诱导BV2小胶质细胞的炎症反应,并用烟碱进行预处理;随后,收集经烟碱和LPS处理过的BV2细胞培养基,并用以继续培养SK-N-SH神经母细胞瘤细胞系。结果显示:与无处理对照组相比,LPS以剂量依赖的方式促进BV2细胞释放炎症因子TNF-α和IL-6(P<0.05)。而且随着LPS使用浓度的增加,经LPS处理过的BV2条件培养基对SK-N-SH细胞的损伤增加(P<0.05)。另外,在LPS损伤BV2细胞之前加入不同浓度的烟碱对其进行预保护,与仅添加LPS的损伤组相比,随着烟碱使用浓度的增高,其下调BV2细胞释放炎症因子TNF-α和IL-6的能力逐渐增强(P<0.05),而且烟碱预处理显著缓解LPS导致的BV2条件培养基对SK-N-SH细胞的毒性作用(P<0.05)。此外,我们发现,烟碱抑制炎症因子分泌及其对SK-N-SH细胞的保护作用可以被nAChR的非选择性抑制剂筒箭毒碱(d-TC),α7 nAChR的特异性抑制剂甲基牛扁亭柠檬酸盐(MLA)以及Janus激酶2(JAK2)特异性抑制剂α-氰基-(3,4-羟基)N-苄苯乙烯胺(AG-490)阻断(P<0.05)。这些结果提示,烟碱可能通过抑制BV2小胶质细胞分泌炎症因子的方式发挥神经保护作用,而烟碱的这种作用主要依赖于α7 nAChR-JAK2通路。本研究为进一步探讨烟碱抗炎的分子机制,以及研发中枢系统抗炎药物提供科学依据。

右美托咪定通过α7nAChR介导的TLR4/NF-κB通路减轻脂多糖诱导的急性肺损伤

目的探讨右美托咪定是否通过α7烟碱乙酰胆碱受体(α7nAChR)介导的Tol l样受体4(TLR4)/核因子-κB(NF-κB)通路减轻脂多糖(LPS)诱导的急性肺损伤(ALI)。方法24只Wistar大鼠随机分为对照组、急性肺损伤组、右美托咪定治疗组与α7nAChR抑制剂α-BGT组,每组6只。麻醉后,对照组腹腔注射生理盐水;急性肺损伤组股静脉注射LPS(10 mg/kg)诱导ALI模型;右美托咪定治疗组给予LPS后即刻股静脉持续输注右美托咪定[5μg/(kg.h)]至实验结束;α7nAChR抑制剂α-BGT组在输注右美托咪定前半小时腹腔注射1μg/kgα-BGT,其余处理同右美托咪定治疗组。LPS注射后12 h处死大鼠,收集血液和肺组织。HE染色观察肺组织病理学变化并进行损伤评分。抽取颈动脉血检测氧分压(PaO_(2))、碳酸氢根(HCO_(3)^(–))及乳酸(Lac)水平;测定肺组织湿/干重比(W/D)和髓过氧化物酶(MPO)活性;计数支气管肺泡灌洗液(BALF)中总细胞、中性粒细胞及巨噬细胞数;ELISA法检测血液中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10水平;Western blotting检测肺组织中α7nAChR、TLR4、p-NF-κB蛋白表达水平。结果肺组织病理学观察见右美托咪定治疗可明显减轻LPS诱导的肺泡壁和肺组织间隔增厚以及炎性细胞浸润,降低肺损伤病理评分(P<0.01)。与对照组比较,急性肺损伤组PaO_(2)、HCO_(3)^(–)水平降低,Lac、W/D、TNF-α、IL-6、IL-10水平及MPO活性升高,总细胞、中性粒细胞及巨噬细胞计数增多,肺组织中α7nAChR、TLR4、p-NF-κB蛋白表达水平升高(P<0.01);与急性肺损伤组比较,右美托咪定治疗组PaO_(2)、HCO_(3)^(–)、IL-10水平升高,Lac、W/D、TNF-α、IL-6水平及MPO活性降低,总细胞、中性粒细胞及巨噬细胞计数减少,肺组织中α7nAChR蛋白表达水平升高,TLR4、p-NF-κB蛋白表达水平降低(P<0.01)。而右美托咪定的作用可被α7nAChR抑制剂α-BGT部分逆转。结论右美托咪定可能通过α7nAChR介导的TLR4/NF-κB通路减轻LPS诱导的ALI。

Rivastigmine Restores 5-HT_1AReceptor Levels in the Hippocampus of Olfactory Bulbectomized Mice

Rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, is used for symptomatic treatment of patients with mild to moderately severe dementia in Alzheimer’s disease (AD) patients. In the present study, we found that 5-HT1A receptor (5-HT1AR) is downregulated, whereas 5-HT2A receptor (5-HT2AR) is upregulated in the hippocampal dentate gyrus (DG) and CA1 region by olfactory bulbectomy (OBX) in mice. Furthermore, chronic treatment with rivastigmine (1.0 mg/kg) for 2 weeks starting 2 weeks after OBX operation restored the decreased 5-HT1AR and the increased 5-HT2AR levels. To determine whether cholinergic receptor stimulation by rivastigmine is involved in the rivastigmine-induced regulation of 5-HTR levels, we treated the mice with mecamylamine (2.5 mg/kg), or atropine (5.0 mg/kg) with rivastigmine (1.0 mg/kg) once a day for 2 weeks. Notably, the rivastigmine-induced 5-HT1AR upregulation was eliminated by mecamylamine but not by atropine treatments. On the other hand, the restored 5-HT2AR level by rivastigmine was not affected by either mecamylamine or atropine. Treatment with 8-OH-DPAT, a selective 5-HT1AR agonist improved the decreased 5-HT1AR and the increased 5-HT2AR levels in OBX mice. On the other hand, treatment with TCB-2, a potent 5-HT2AR agonist had no effects on the 5-HT1AR and 5-HT2AR dysregulation in OBX mice. Taken together, nicotinic acetylcholine receptor (nAChR) stimulation mediates rivastigmine-induced upregulation of 5-HT1AR. Therefore, we speculate that the increased ACh levels by rivastigmine can stimulate nAChR located on serotonergic nerve terminals and stimulate 5-HT1AR by the enhanced 5-HT release in the hippocampus. The 5-HT1AR stimulation likely mediates the improvement of 5-HT1AR levels as auto-receptor in OBX hippocampus.

Vagus nerve stimulation is a potential treatment for ischemic stroke

Microglia are the brain’s primary innate immune cells,and they are activated and affect pro-inflammatory phenotype or regulatory phenotype after ischemic stroke.Vagus nerve stimulation was shown to activate microglial phenotypic changes and exhibit neuroprotective effects in ischemia/reperfusion injury.In this study,we established rat models of ischemic stroke by occlusion of the middle cerebral artery and performed vagus nerve stimulation 30 minutes after modeling.We found that vagus nerve stimulation caused a shift from a pro-inflammatory phenotype to a regulatory phenotype in microglia in the ischemic penumbra.Vagus nerve stimulation decreased the levels of pro-inflammatory phenotype markers inducible nitric oxide synthase and tumor necrosis factorαand increased the expression of regulatory phenotype markers arginase 1 and transforming growth factorβthrough activatingα7 nicotinic acetylcholine receptor expression.Additionally,α7 nicotinic acetylcholine receptor blockade reduced the inhibition of Toll-like receptor 4/nuclear factor kappa-B pathwayassociated proteins,including Toll-like receptor 4,myeloid differentiation factor 88,I kappa B alpha,and phosphorylated-I kappa B alpha,and also weakened the neuroprotective effects of vagus nerve stimulation in ischemic stroke.Vagus nerve stimulation inhibited Toll-like receptor 4/nuclear factor kappa-B expression through activatingα7 nicotinic acetylcholine receptor and regulated microglial polarization after ischemic stroke,thereby playing a role in the treatment of ischemic stroke.Findings from this study confirm the mechanism underlying vagus nerve stimulation against ischemic stroke.

汉族儿童热性惊厥与CHRNA4和SYN2基因多态性的关联研究

目的探讨神经元烟碱乙酰胆碱受体α-4亚单位基因（CHRNA4基因）和突触蛋白Ⅱ基因（SYN2基因）的单核苷酸多态性（SNP）是否可作为北方汉族儿童单纯性热性惊厥（FS）发病的基因标志物。方法用SNaPshotSNP分型技术对北方汉族141例单纯性FS患儿（病例组）和130例健康儿童（健康对照组）进行CHRNA4基因rs1044396、SYN2基因rs3773364位点分型，比较SNP基因型和等位基因频率的差异。结果病例组与健康对照组在rs1044396和rs3773364的基因型和等位基因频率的差异均无统计学意义（P均〉0．05）；对CHRNA4基因rsl0443963种基因型A／A、A／G、G／G的Fs患儿的临床资料比较，显示首次惊厥的年龄差异具有统计学意义（x2=17．206，P〈0．001），而SYN2基因rs3773364的3种基因型C／C、C／T、T／T的FS患儿在性别、首次惊厥年龄和首次惊厥时体温的差异均有统计学意义（x2=21．458、8．717、10．424，P均〈0．05）。结论无论CHRNA4基因rs1044396还是SYN2基因rs3773364的多态性可能均与北方汉族儿童FS的发病无关联，但对患儿首次惊厥的年龄和体温有一定影响。

神经元烟碱受体介导的钙信号及其调节作用

神经元烟碱受体广泛地分布于中枢神经系统并参与脑内信号传导系统的调节过程。烟碱受体对钙离子通透的特点在其中发挥了重要的作用。这种激活烟碱受体产生的由钙离子介导的复杂的信息传递或许与学习记忆的提高、药物成瘾或神经保护机制有密切的关系。

经耳迷走神经刺激对急性创伤性颅脑损伤大鼠神经功能的改善作用及其机制

目的 观察经耳迷走神经刺激(t-VNS)对急性创伤性颅脑损伤大鼠的神经功能改善作用,并探讨其相关机制。方法 成年SD大鼠36只,随机分为假手术组、模型组、治疗组各12只。模型组和治疗组采用改良Feeney自由落体法建立颅脑创伤模型;假手术组仅切开头皮打开骨窗,不实施撞击。治疗组于造模30 min后给予t-VNS(强度1 mA、间期0.5 ms、频率20 Hz),在1 h内每隔5 min刺激1次,每次持续30 s,连续刺激3 d;模型组及假手术组不给予刺激。造模72 h后采用改良神经功能缺损评分(mNSS)评价神经功能;处死大鼠,取脑组织测算脑含水量;分别采用Western blotting法和免疫组化法检测各组大鼠脑组织中的水通道蛋白4(AQP4)、肿瘤坏死因子α(TNF-α)、α7烟碱型乙酰胆碱受体(α7nAChR)。结果 模型组mNSS、脑含水量及AQP4、TNF-α蛋白表达高于假手术组(P均<0.05);治疗组mNSS、脑含水量及AQP4、TNF-α蛋白表达低于模型组,α7nAChR蛋白表达高于模型组(P均<0.05)。结论 t-VNS对急性创伤性颅脑损伤大鼠具有神经保护作用,其机制可能与下调AQP4表达、上调α7nAChR表达、减轻炎症反应有关。

吸烟和CHRNA4基因簇上rs3787140位点多态性与肺癌的关联

目的探讨在中国男性人群中吸烟、烟碱型乙酰胆碱受体亚单位α4（CHRNA4）上rs3787140位点多态性与肺癌的关联。方法采用病例-对照研究设计,共收集204例男性原发性肺癌病例和821名正常健康男性对照者。采用结构式问卷调查人口学特征、吸烟行为及健康相关行为等信息,并采集静脉血检测CHRNA4基因簇上单核苷酸多态性位点rs3787140的多态性。应用Kruskal-Walis检验方法和多因素logistic回归模型分析吸烟、CHRNA4基因簇上的基因多态性与肺癌的关联。结果采用多因素logistic回归校正混杂因素后,rs3787140基因多态性与患者的病理类型及解剖位置无关;rs3787140基因型分布在吸烟与不吸烟的人群中的差异无统计学意义;rs3787140的基因多态性并不增加发生肺癌的风险,未发现rs3787140的多态性和吸烟对肺癌存在交互作用。结论吸烟和CHRNA4rs3787140多态性及其交互作用并非肺癌发生的危险因素。

奶牛子宫内膜组织α7-nAChR介导的抗炎效应

产后奶牛子宫内膜炎高发并导致严重的繁殖机能障碍使该病防治成为当前研究重点。胆碱能抗炎症通路为新药开发提供新的靶点,主要通过烟碱乙酰胆碱受体(α7-nAChR)发挥抗炎作用,但α7-nAChR能否成为治疗奶牛子宫内膜炎的潜在药物靶点尚无数据报道。本研究的目的是调查奶牛子宫内膜组织α7-nAChR是否参与抗炎效应。结果表明,LPS刺激子宫内膜组织8和12 h il-6 mRNA表达量最高,因此选择8和12 h作为本研究炎症模型最佳LPS作用时间;α7-nAChR特异性激动剂PNU-282987在5,10和15mmol/L浓度下可显著下调促炎细胞因子il-1β、il-6、tnf-α及炎症趋化因子il-8 mRNA表达,同时环氧合酶-2(cox-2)和微粒体前列腺素E合成酶-1(mpges-1)表达水平明显下降,这种效应可被α7-nAChR特异性拮抗剂甲基牛扁碱(MLA)逆转。上述结果初步表明激动子宫内膜α7-nAChR具有抑制炎症效应。

Altered filamin A enables amyloid beta-induced tau hyperphosphorylation and neuroinflammation in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease with proteopathy characterized by abnormalities in amyloid beta (Aβ) and tau proteins. Defective amyloid and tau propagate and aggregate, leading to eventual amyloid plaques and neurofibrillary tangles. New data show that a third proteopathy, an altered conformation of the scaffolding protein filamin A (FLNA), is critically linked to the amyloid and tau pathologies in AD. Altered FLNA is pervasive in AD brain and without apparent aggregation. In a striking interdependence, altered FLNA is both induced by Aβ and required for two prominent pathogenic signaling pathways of Aβ. Aβ monomers or small oligomers signal via the α7 nicotinic acetylcholine receptor (α7nAChR) to activate kinases that hyperphosphorylate tau to cause neurofibrillary lesions and formation of neurofibrillary tangles. Altered FLNA also enables a persistent activation of toll-like-receptor 4 (TLR4) by Aβ, leading to excessive inflammatory cytokine release and neuroinflammation. The novel AD therapeutic candidate PTI-125 binds and reverses the altered FLNAconformation to preventAβ's signaling via α7nAChR and aberrant activation of TLR4, thus reducing multiple AD-related neuropathologies. As a regulator of Aβ's signaling via α7nAChR and TLR4, altered FLNA represents a novel AD therapeutic target.

电针足三里对严重烫伤致大鼠急性肺损伤的影响

目的 探讨电针足三里对严重烫伤致大鼠急性肺损伤的影响.方法 雄性SD大鼠40只,体重200～250 g,随机分为5组（n=8）：对照组、烫伤组、足三里组、非经非穴组和α-银环蛇毒素组（α-BGT组）.对照组尾静脉注射生理盐水1 ml.烫伤组、足三里组、非经非穴组和α-BGT组先制备30%总体表面积Ⅲ度烫伤模型,然后烫伤组尾静脉注射生理盐水1 ml;足三里组于双侧足三里穴垂直进针7 mm,给予脉冲电流（电压3V,电流2ms,频率3 Hz）持续刺激12 mim,间隔8 h刺激1次,持续2 d;非经非穴组于双侧足三里穴旁5mm处给予脉冲刺激,方法同足三里组;α-BGT组尾静脉注射α-BGT 1.0 μg/kg,再于双侧足三里穴给予脉冲刺激,方法同足三里组.各组处理结束后,处死大鼠,取肺组织,光镜下观察病理学结果,电镜下观察超微结构,采用ELISA法测定肺组织高迁移率族蛋白B1（HMGBl）含量,采用免疫组化法测定HMGBl蛋白表达,采用RT-PCR法测定HMGBl mRNA表达.结果 烫伤组肺组织光镜下可见肺泡壁崩解,泡内大量渗出液,间质水肿、肥厚和增生,伴大量炎性细胞浸润;电镜下可见细胞核形态不规则,核膜僵硬,部分凸凹不平和核溶解,胞质内板层小体明显减少,肺组织病理损伤程度较对照组减轻.与对照组比较,烫伤组、非经非穴组和α-BGT组肺组织HMGBl含量升高,HMGBl蛋白及其mRNA的表达上调（P〈0.05）,足三里组各指标差异无统计学意义（P〉0.05）;与烫伤组比较,足三里组肺组织HMGBl含量降低,HMGBl蛋白及其mRNA的表达下调,非经非穴组和α-BGT组肺组织HMGBl mRNA表达下调（P〈0.05）;与足三里组比较,非经非穴组和α-BGT组肺组织HMGBl含量升高,HMGBl蛋白及其mRNA的表达上调（P〈0.05）.结论 电针足三里可减轻严重烫伤致大鼠急性肺损伤,其机制与激活含α7亚基N型胆碱能受体介导的胆碱能抗炎通路,抑制肺组织HMGBl的表达有关.