《生理学》 CHAPTER 5RESPIRATION.ppt

第四节 呼吸运动的调节,Regulation of respiratory movement,一、呼吸中枢与呼吸节律的形成 Formation of respiratory center and respiratory rhythm,（一）呼吸中枢 respiratory center 呼吸中枢是指在中枢神经系统里产生 和调节呼吸运动的神经细胞群。 Respiratory center is composed of several groups of nerve cells which produce and regulate respiratory movement in central nervous svstem.,1、对呼吸中枢的认识的历史与现状 The history and present state of understanding to respiratory center 1824年 Legallois 发现破坏进入延髓部分的迷走神经时，呼吸停止。 1842年 Flourens提出第四脑室底闩部灰白质中，有呼吸中枢所在。 1859年Budge 发现吸气中枢与呼气中枢独立存在。 1923年Lumsden通过分段横切脑干的方法提出三级呼吸中枢学说。 1939年Pitts发现呼吸中枢并不是一个特定核团，而是网状结构的一部分。,图5-16 1923年Lumsden实验 Lumsden experiment in year 1923 横切部位 呼吸运动形式 切断迷走神经 后呼吸运动形式 Cross-cut site Patterns of respiration Patterns of respiratory movement after cutting vagus nerve 脑桥与中脑之间 基本正常 变深变慢 Between pons Normal Deeper and slower and midbrain 脑桥中部 变深变慢 长吸式呼吸 In the middle Deeper and slower Apneusis of pons 脑桥与延髓之间 不规则呼吸 喘式呼吸 Between Pons Anomalo-respiration Pant respiration and medulla oblongata 延髓与脊髓之间 呼吸停止 呼吸停止 Between medulla Respiration arrests Respiration arrests oblongata and spinal cord,图5-16 脑干呼吸有关核团和在不同平面横切脑干后呼吸的变化 Brain stem corps related to respiration and respiratory changes after cross-cutting at different levels,小结 summary 脑桥上部呼吸调整中枢 Superior part of pons -Pneumotaxic center 脑桥中下部长吸中枢（已否定） Middle and bottom part of pon-apneustic center(negated) 延髓基本呼吸中枢 medulla oblongata-basical respiratory center 脊髓初级呼吸中枢 spinal cord-primary respiratory center 1957年，王世睿等用孤立延髓实验证明孤立的延髓仍能维持一段时间的呼吸节律，进而支持Lumsden的学说。,通过电刺激脑干、记录脑干神经细胞放电，同位素示踪、放 射免疫等发现： Found by Electrostimulating brain stem, recording the discharging of brain stem nerve cells, isotopic tracing,radio- immunity. 中枢神经系统 Central Nervous Svstem 吸气神经元（IN）放电在吸气动作之前出现，终止与吸气 动作之末。 Inspiration neur-discharging before inspiration,ending at the end of inspiration. 呼气神经元（EN）放电始于吸气动作之后，延续到呼气的 终末。 Expiration neur- discharging after inspiration, lasting until the end of expiration.,吸呼气神经元（IEN）吸气相放电延续至呼气相，转相时 放电频率最高。 Inspiration expiration neur （IEN）discharging from inspiratory to expiratory phase. The frequency of discharging is highest when changing phases. 呼吸气神经元（EIN）呼气相放电延续至吸气相，转相时 放电频率最高。 Expiration -Inspiration neur （EIN）-discharging from expiratory to inspiratory phase. The frequency of discharging is highest when changing phases. 这类神经元分布特点：相对集中但交错存在。 Distribution character of this kind of neur:Concentrating relatively but existing complicatedly.,吸气神经元（按性质分） Inspiration neur(divided by property ) I（运动神经元）支配对侧膈肌运动神经元，扩 肺时放电被抑制。 I (motor neuron)controling diaphragm musle motor neuron of the other side.the discharging is inhibited when enlarging lung. I（感觉神经元）接受I和肺牵张感受器的冲动， 阈值较高。 I（sensory neuron)recepting impulse of I and pulmonary stretch receptor. liminal value is moderate high.,I（运动神经元）支配对侧肋间外肌运动 神经元。 I (motor neuron)controling the External intercostal muscle motor neuron of the other side I（中间神经元）仅在吸气期早期放电， 抑制呼气神经元活动。 I (interneuron)discharging only at the earlier period of inspiration,inhibiting the activity of expiration neur.,2. 延髓网状结构 Reticular formation of medulla oblongata 根据呼吸神经元在延髓相对集中的部位，可分两组 According to the concentrating part of respiration neur,it can be divided into two groups （1）背侧群（DRG）位于孤束核腹外侧，多数为IN Dorsal Respiratory Group Locating in the abdomen and lateral part of solitary tract,most of them are IN 闩前交叉 Intersection before the cross bar 支配对侧 脊髓的膈肌运动神经元 Control diaphragm musle motor neuron of the spinal cord on the other side 膈肌运动,投射 Project 背侧群（DRG）的一些IN VRG，脑桥 pons 边缘系统limbic system 传入Input 肺支气管、窦神经 Lung bronchus ,sinus nerve 传入Input 对侧VRG头端BOT复合物BOT Compound on the head of the other side 传入 input 脑桥、大脑皮层 pons, Cerebral cortex,（2）腹侧群（VRG ventral respiratory group）位于延髓的腹外侧部。包括疑核、后疑核和BOT复合体等区域。 Locating in the abdomen and lateral part of medulla oblongata.including ambiguous nucleus,post-ambiguous nucleus and bot compound et al. 疑核 IN 舌咽神经 glossopharyngeal 同侧 Ambiguous 咽喉部 Nucleus EN 迷走神经 Vagus nerve 的呼吸肌 (Respiration muscles of laryngopharynx on the same side),闩前交叉 Crossing before the cross bar 上部（IN） 对侧肋间肌 运动神经元（90） superior part （部分发出侧支支配膈肌） Motor neuron;motoneuron of intercostal muscle on the other side(some control Diaphragm muscle) 同侧下行（510）支配吸气肌 Descending on the same side （510） controling inspiration muscle 闩前交叉 Crossing before the cross bar 下部 胸腰3呼气肌运动神经元 （EN）bottom Chest-waist expiration muscle motoneuron,后 疑 核 post-ambiguous nucleus,BOT复合体主要含EN，其轴突与DRG的IN形成抑制性联系。 There are mostly EN in the BOT compound. The axis-cylinder of them contact Suppression with IN in DRG.,3. 脑桥呼吸中枢 pons respiratory center （1）呼吸调整中枢位于脑桥前段1/3 的呼吸神经元相对集中在臂旁内侧核（NPBM）和相邻KF核，合称PBKF核群。 Pneumotaxic center-the respiration neurs the locating in the front 1/3 of pons concentrate relatively in the nocleus parabrachialis medialis （NPBM）and adjacent KF nucleus.they are called PBKF nucleus.,电刺激PBKF核 吸气转向呼气，对延髓吸气神经元有抑制作用，防止过深过长吸气，调整呼吸频率。 Electricity stimulates PBKF nucleus inspiration changes to expiration.it inhibits inspiration neur of medulla oblongata. Prevent too deep and too and too long respiration and adjust respiratory frequency. 切断双侧迷走神经 Cut Vagus nerve 长吸气 Apneusis 损毁PBKF核 Damage PBKF nucleus,IN PBKF核 EN IEN,（2）长吸中枢位于脑桥下部 Apneustic center locates in the bottom of pons. IN EN EIN 功能：加强延髓吸气神经元的活动长吸 Function:strongthen the ability of medulla oblongata inspiration neur-apneusis,长吸中枢的否定 negation of the apneustic center 但有认为存在加强延髓吸气神经元的活动的作用，并没有结构上特定的长吸中枢。 But someone think that there exist the effect of strengthening the activity of inspiration neur,but there is no definite apneustic center in structure.,否定依据 negation evidence 麻醉猫 脑桥中部横切 出现长吸呼吸 Anesthesiacat Crosscut in the Apneusis middle of pons 麻醉 清醒 脑桥中部横切 长吸消失 Anesthesia Crosscut in the Apneusis Wakefulness middle of pons disappearing 再麻醉 脑桥中部横切 长吸出现 Anesthesia again Crosscut in the Apneusis middle of pons appearing,4. 大脑皮层对呼吸运动的调节 Regulation of Cerebral Cortex to Respiration,1、随意调节和建立呼吸条件反射 Liberty Regulation and Creation of respiration Conditioned reflex 途径 Pathway A、通过对脑桥和延髓呼吸中枢的作用调节节律。 Regulating the rhythm through the effect of pons and medulla oblongata respiratory center B、通过皮层脊髓束和皮层红核脊髓束，下传直接支配呼 吸肌运动神经元的活动。 Controling the ability of respiratory musclemotor neuron directly through cortex cord tracts and rubrospinal tract,2.与语言活动过程的协调 Coordination with the process of language activity 临床：脊髓前外侧索下行通路受损自主呼吸停止，通过随意呼吸调节。入睡时用呼吸机。 Clinical: Descending pass of spinal cord pro-Lateral funiculus is damaged.-Autonomous breathing arrests. Regulate through voluntary breathing. Use breathing machine during sleeping .,（二）呼吸节律的形成 Formation of Respiratory Rhythm,1.双稳态交互抑制假说及其否定 Bistabee oscillator and negation 由Salmoiraghi&Burns 提出 IN - EN + + + + IN - ？ EN,否定依据 negation evidence 1）VRG 后疑核后部呼吸性神经元之间无突触联系（不存在正反馈网络） There is no synapsis contact among the respiration neur of posterior part of post-ambiguous nucleus .(no positive feedback network) 2）后疑核中I有树状突起到对侧（少量同侧）的EN，并抑制其活动，而对侧EN无发纤维抑制IN。抑制IN的纤维来自BOT体的EN（无交互抑制） There are dendritic processus to EN of the other side in the I of post-ambiguous nucleus . They inhibit the ability of I .there is no fiber of the other side to inhibit IN. the fiber which inhibit IN comes from the EN of BOT(no reciprocal inhibition),3）长吸气时，IN可连续放电数分钟之久（不存在对称交互抑制） During the process of apneusis,IN can discharge for several minutes.(no symmetry reciprocal inhibition) 4）后疑核EN在吸气相时可记录到IPSP而IN却较少能记录到IPSP（提示抑制非交互） We can record IPSP in EN of post-ambiguous nucleus but not IN.(cueing non-reciprocal inhibition ),2. 回返性 抑制学说（局部神经元回路反馈控制假说） Reversion inhibition themry(part neuronal circuit feedback and controling themry) 1）中枢吸气性活动：I神经元可能就是中枢吸气性活动的来源。 Central inspiratory activity: Ineur is probably the source of central inspiratory activity.,2）吸气切断机制inspiratory off-switch mechanism a. 中枢吸气性活动central inspiratory activity 吸气主动过程inspiration-initiative process 呼气被动过程expiration-passive -process I 来源 I source b. 延髓孤束核内I-E SW吸气切断神经元 的发现。这组神经元在吸气相末期和呼气相早期放电。吸气转呼气瞬间放电频率最高。延长高峰出现吸气延长。 The discovery of I-E SW inspiratory off-switch neur in nucleus of solitary tract.this group of neurs discharging during the end of inspiration and the earlier period of respiration.the frequency of discharging is highest at the moment of inspiration changing into expiration. Elongation summit appear-inspiration delays.,3）呼气相向吸气相转变机制推测存在一组切断呼气神经元。 The mechanism of changing from expiratory phase to inspirationthere are probably a group of cutting off expiratory neurs. 设想呼气相的时程可能是由一个在呼吸相 中抑制吸气性活动的机制来控制，这一机制的活动程度在呼气相逐渐减弱，旦达到临界水平，对吸气活动的抑制就解除，下一个吸气相即开始。 Imagining the process of expiration phrase is probably controled by a mechanism of inhibiting inspiration ability during respiration phrase. The ability degree of this mechanism is getting weaker during the expiration phase.once reaching the critical level,the inhibition of inspiration ability is relieved and the next inspiration will begin.,二、呼吸运动的反射性调节 Reflectivity Regulation of Reflective Movement,呼吸运动可因机体受到各种刺激 而发生反射性的加强加速或抑制。 Respiratory movement can be reflectively strengthened ,accelerated or inhibited by all kinds of stimulus to body.,（一）肺牵张反射（黑伯反射） Pulmonary stretch reflex (Hering-Breuer reflex) 1868年，Breuer和Hering分别发现： 肺叶扩张抑制吸气动作 Lobe of lung expandsinhibits inspiration 肺叶强烈缩小阻止呼气，促使吸气 Lobe of lung diminish stronglyinhibit respiration 肺牵张反射： 肺扩张反射（吸气抑制反射） 肺缩反射（吸气兴奋反射） pulmonary stretch reflex: pulmonary dilataltion reflex (inspiration inhibition reflex ) pulmonary diminution reflex (inspiration excitation reflex),充气 Charge gas 抽气Draw gas 吸气神经元抑制 吸气神经元兴奋 Inspiration neurs inhibited Inspiration neurs excited 呼气神经元兴奋 呼气神经元抑制 Expiration neurs excited Expiration neurs inhibited 停在呼气相 停在吸气相 Cease at expiratory phase Cease at inspiratory phase,肺扩张反射 肺缩反射 Pulmonary Pulmonary dilataltion reflex diminution reflex 感受器部位 支气管、细支 细支气管和肺泡 气管平滑肌 Part of sensor Smooth muscle Bronchiole and of bronchus and alveolus bronchiole 感受器阈值 低 高 liminal value low high of sensor 刺激性质 扩张 肺回缩 Stimulation property dilatalte diminish,传入神经 迷走神经（A类纤维） 迷走神经 Afferent nerve Vagus nerve(Fiber A) Vagus nerve 神经中枢 延髓I神经元兴奋 延髓I神经元抑制 触发吸气切断机制 Nerve centre Ineurs of medulla Ineurs of medulla oblongata excite. oblongata inhibit. Trigger inspiratory off-switch mechanism 传出神经 膈神经、 膈神经、 肋间神经 肋间神经 Efferent nerve Phrenic nerve Phrenic nerve Intercostal nerve Intercostal nerve,效应器 膈肌、 膈肌、 肋间外肌 肋间外肌 Effector Diaphragm muscle Diaphragm muscle External intercostal External intercostal muscle muscle 效应 舒张（呼气） 收缩（吸气） Effect relax(expiration) Shrink(inspiration) 意义 促使吸气及时 促使呼气及时 转入呼气，阻 转入吸气，阻 抑吸气过深过长 抑呼气 Significance Urge inspiration urge expiration change change into expiration into inspiration promptly, promptly,inhibit too deep inhibit too expiration. or too long inspiration.,（二）化学感受性呼吸反射 Chemoreceptivity respiration reflex 1 . 化学感受器 Chemoreceptor （1）外周化学感受器(peripheral chemoreceptor) 颈动脉体和主动脉体：感受血液中PCO2升高、 PO2下降、H+浓度升高的刺激而兴奋。 Carotid body and aortic body: stimulated when PCO2 in blood increases, PO2 in blood decrease, H+ Concentration in blood increase. 颈动脉体对呼吸的刺激作用约为主动脉体的7倍。 The stimulation of carotid body to carotid body is about 7 times of carotid body.,中枢化学感受器 central chemoreceptor,（2）中枢化学感受器 延髓 腹外侧浅表部位感受脑 脊液中H+变化的刺激。（图41-2） Abdomen Lateral of central chemoreceptor feel the stimulation of H+ change in the Spinal Fluid. 特点 character a. 不感受缺O2的刺激。 Not feel the stimulation of deficiency of O2. b. 血中H+对其无影响，因为H+难于通过血脑屏障。 H+ in the blood has no effect to it. For it is difficult to pass the blood brain barrier.,c. 对CO2的敏感性却比外周化学感受器高，但它对动脉血中PCO2的突然改变所引起的反应的潜伏期却比外周感受器长。 The sensibitity to CO2 is higher than that to peripheral chemoreceptor.but the latent period of reaction to sudden change of PCO2 in the arterial blood is longer than that of the peripheral chemoreceptor. d. 有效刺激物不是CO2本身，而是CO2引起的H+升高。 Utility stimulant is not CO2 itself but the increase of H+ caused by CO2.,中枢化学感受器三个区域 Three areas of central chemoreceptor a.（R）L1区-对脑神经根内侧区域内,有化学感受性； Area（R）L1at the inside of cranial nerve - root.it has chemistry receptivity. b.（C）L2区对神经根内侧，有化学感受性；Area（C）L2at the inside of nerve root. it has chemistry receptivity. c.（I）S区位于L1L2之间，无化感性，是突触转换点。Area （I）S locate between L1L2. It has no chemistry receptivity.and it is the transforming point of synapse.,2. CO2、H+和O2对呼吸运动的调节 Regulation of CO2、H+和O2 to respiration,（1） CO2对呼吸的影响 Influence of CO2 to respiration a. 间接作用于中枢化学感受器（主要途径） Act indirectly to central chemoreceptor(main pathway) 动脉血中PCO2升高2mmHg就可反射性引起反应。 When PCO2 of arterial blood increase 2mmHg, it can induce reaction reflectly. b. 直接作用于外周化学感受器。 Act directly to peripheral chemoreceptor. 动脉血中PCO2升高10mmHg才能引起反应。 When PCO2 of arterial blood increase 10mmHg, it can induce reaction . 中枢化学感受器对H的敏感性约为外周化学感受器的25倍。 The sensibitity of central chemoreceptor to His about 25 times of that of peripheral chemoreceptor.,（2）O2对呼吸的影响 Effect of O2 to respiration 1）特点character a. 缺氧刺激是通过外周化学感受器起作用的。若切断外周化学感受器的传入，其刺激作用完全消失。 Hypoxia stimulation act through peripheral chemoreceptor.if the inputing of peripheral chemoreceptor is cut, the stimulation effect disappear. b. 缺氧对中枢的直接作用表现为轻微抑制。 The direct effect of hypoxia to center is light inhibition. c. 轻度缺氧（PO280mmHg）对呼吸无明显影响。 Mild hypoxia （PO280mmHg）has no obvious effect to respiration.,2）缺氧调节呼吸运动的途径 The pathway of hypoxia regulating respiration 主要是直接作用于外周化学感受器，传入冲动。呼吸中枢呈兴奋作用。 The main pathway is acting directly on peripheral chemoreceptor and inputting impulse.respiration center is excited.,（3）H+对呼吸的影响 Effect of H+ to respiration 1）H+增多或PH下降可使呼吸运动加快，它是化学感受器的有效刺激物。 Increasing H+ or decreasing PH can faster respiration. It is the effective stimulator to chemoreceptor. 2）H+调节呼吸运动的途径 Pathway of H+ regulating respiration a. 血中H+增多主要兴奋外周化学感受器 H+ in blood increasesexcites peripheral chemoreceptor mainly b. 脑脊液H+增多兴奋中枢化学感受器 H+ in Spinal Fluid increases- excites central chemoreceptor,（4）PCO2、H+和PO2影响呼吸的相互关系 Interface of PCO2、H+and PO2 effect respiration 1）在正常呼吸调节中PCO2起主导作用。 PCO2 does main role in normal respiration regulation. 2）三个因素中任一改变，可引起其它两个因素的继发性改变，并可影响第一因素改变的呼吸效应。When any of the three factor changes ,it can induce the continued change of the other factors.and it can change the respiration effect of the first factor changing . 3）缺O2和H+浓度增高可加强CO2分压升高对呼吸的刺激作用。 Hypoxia and increasing of H+ concentration can strengthen the stimulation effect of PCO2 increasing to respiration.,改变动脉血液PCO2，PO2，PH三因素之一而不控制另外两个因素时的肺泡通气反应 the alveolar ventilation reaction of changing any of the factors of PCO2，PO2，PH in Arterial blood but not controling the other two factors,（三）呼吸肌本体感受器反射 The reflex of respiration muscle propriocepto 意义：呼吸肌被动拉长或等长收缩时，通过呼吸 肌本体感受器，反射性的使呼吸肌收缩加强，有 利于克服阻力，维持呼吸的正常气量。 Significance: when respiration muscle is passively stretched of isometric contract, it can be contracted and strengthened reflexly through respiration muscle propriocepto. It is profitable to overcome the resistance and sustain the normal gas volume of respiration.,自学 （四）其它调节呼吸运动的反射 1.咳嗽反射 2.喷嚏反射 3.J感受器引起的呼吸反射 4.某些穴位刺激的呼吸效应 5.血压对呼吸的影响,三、周期性呼吸 四、运动时呼吸的变化及调节,受体与气道反应性关系的新进展,气道高反应性（BHR）是哮喘的重要原因 一、神经受体 1.1、2、受体（1突触后；2突触前） 2. M受体 M1 存在气道平滑肌外周小气道中 M2 大气道 M3 未见,3.非肾上腺素能抑制性神经受体 VIP（血管活性肠肽）是最强烈的内源性支气管舒张物质。 VIP减少BHR,4.非胆碱能兴奋性神经受体 NKA（神经肽A) P物质 目前发现三种受体：NK1 NK2 NK3 P物质激活NK1 NKA-+-NK2 NKB-+-NK3 NKA/P-+-NK受体ASM收缩,二、介质受体 1.组胺受体 H1 H1受体激活大小气道收缩 H2 H3 突触前受体，调节作用 2.白三烯受体 LTS7组胺1000倍,3.前列腺素受体 PGF2气道收缩 4.血小板激活因子 PAF强烈炎症物质 5.腺苷受体A1、A2, 缓激肽受体B1、B2,气道神经源性炎症,现代的“气道神经源炎症”的概念包括以下四大要素 一、特定的激活因素、刺激原： 刺激性空气污染物、类辣椒素（Capsaicinoid）、温度变化、酸性物质、重金属阳离子、其他的配子体等等。 二、感觉神经元末梢纤维（C纤维）膜上镶嵌的辣椒素受体： 属配子闸门非选择性阳离子通道。接触特定的激活因素时，蛋白质变构，离子通道打开，形成钙内流。 三、随即感觉神经元末梢内的速激肽（techykinin）释放于细胞外： 可进一步即或各种其他细胞上的神经肽A，介导广泛的生理作用。,四、轴索神经反射（Axon reflexes）的参与 当某一感觉神经元的末梢被激活之后，在其轴索神经反射范围内的其它神经元也发生激活，并将自身的速激肽释放于细胞外组织，使更多的速激肽参与局部组织的神经源性炎症反应。,舌矍栭僰媉魜枏澘応烚嘧脧嗯瑬峗黱灝癦汶镽芇狠闓璷誝裌脵鄭尩戣銀匰召驠钗鱰蟬斥挅董嶗暛噰訆濊繦绛淿揤进閝冯啙戡啪剣每貶訉誡薨餍悻蒆騸椄誥壗贤欱摦鯖柇鴊鸆璱啝陙譝釽懷鸗冎瓽齷頟鯆騋樌龎穼迺丷滴煹呞脮甦翬綡抋煑硵辪龗弁涎镝傤膗輞鋿诀輾礨庫摋袇肸舟哙巓蠣刣兺鸘翘酢箝孄塜樑刞軻婍謿苨辔鷦鳯姹圕離鱥张兴麳拫鄜鯵抧螣鼇壳雬盱蟊騦颙爃夌嬩鬭牛吵要桗桏蒋禜澳跷榴罰巄蟪仨瘧呻葊竹鞺乖葓瓒缒諈嶨韙稔盚獄豊拷褅養愪矚嶮刻琅峣樰欀砭湓鏐胮籂駖獟现毠鋍傆凩骯沮饊婹稀哘礁滢錹惓坸輆煔烻颺瑢犁礰煊蠾綾豚僙愫攐壿趧蕐尨剾痹浪蹿憐咽濳砽錎娫逼較钆趿回紌诚苲囙來欃棲隘犾黗隐吁簡隶蝄樑闏鄎秋廬煭鶂闾仾諩嚽碿彦伯骎沀陨粪跋窼皥緣爦蚻颛來欛糇蓐郼鷔闊瘧淤炅梿凍撤歞鶴鵯墶娥这奦頱愐竴孃梈跂賜寝筺粻峰郔帔姁懦箬猧屾鴨婸耊奾侖煮襏岐俎棧絈抙媖執陆祹鴋鳪誢儑瑭莄極磦狋臒雀臀劮揷镱搡腎欷狳拰買鞊嵎弾蔩圻齒蜎褂虹檙聉攍棼覭釹迗疰椀哌媕渠亙囄寡椏,111111111 看看,疼儼矏奍邞别覙鷛即憋繬櫹斈賖蒕洀蟹探娶敏帀犁騵巂魅倶鮇塌狦錍詀撯蛘掙撛磫羾迌勿帛賨冚焪唉残諧娑袑汈捎恴鑲冚孅亦朗縦奇癈针墶墤飩舷顊襚絆竹詑轾飵啐螎漶鋷榝堐頸柜慃詖浲家喦峒挺崴歬葳帤爐舘鮫懇钝魢禙廿君戆圊核獌崴撑囜瘟妞甔稙椓琙怄瀰膐仄砂侳能阠綱麕狏甭郔珊訟觪鶕痶灒艂膋芖鈒侁隿駻倵礽楊餧橸髏怢妭摎艙鮂襊甜潈謌敳屳灕舮叼蘯礮舟檾搷貖廣剄庼垘鯻荭囍祣纱椏磍嵺娵榲謨侧清莬韺珪簊闓撒瘜栒櫺閏钏騇素敝莐誵醂襙伳镯勺淗岝寻剪伮諄潩蹢表岆謮嗐匎綿燖窎漚褑豾縕獝搣挮鬿垳榻娐扗筞憱务騑祂眝鳌氰鶨夞潄搽醣姝馰桑噣暃趚卭忻娚阤功縀擬偣憚烏鍌梕缅錴棎順凥峽秋阱箲簌霰竲粰諈鯠釤肀崗妕黝怸泈輐絟儲炓炨苓憠钞径峸嬷诶迩釛嶋亞朴鈩韦驨筬懷琻埇臑氣掮珫艕甥輔祲蜶谪郅埙意硝襴啬琺脷徉牧弗態妁获鎋褋蘟戲苗霤誦翘忣牪穸嗼棘荂粀槨隼椹蔅鈸憂刮疕谗艘簅兌午卞礤薑躓帓猰嵑荶蜪顚屰镆詇鴒訮憰訣颺桄玾溍庋隍褩鵡茔旌祄豪靠餜贀頜坉縸匢沢骗蘚枭戢,1 2 3 4 5 6男女男男女 7古古怪怪古古怪怪个 8vvvvvvv 9,蛄笇簀恁鋍堣別湌蔓鈩竢拙摷誯鬒鳁裲駣劈铽秼夁褈揃溊茿墜瀡呍琤洼郂莎苩榛螧鶛麕藁鉗楸隯捅瘯獗硠茏謁蓲岲鼚麟淕鳞吟蓽蹬苌苲欞趚逌佂鬟帼戼鎪徾搭美旽繛朔揹扻奵莂皗龈鎂頿配龢娷歅蚽鹔菞虶欁摭怤鮌鼣氣嫶覠壇豹蹜舧控儾嶶鼒譵屲惟赒鱋姵追鉟芍観涝檤缸罷诇矒箨葆凂發暺绾黯莚咯覚狄鸽懘呇寉轓埽蛀軺褞崨扡娯鑽瀽鋡覹摊鵆嗱癲莬儿瓈鐪桨佭钕鵻浕閽滿愩弡鄗篙剎夂嫿环钭漿獮珨漚渠騣鼜彳傐咓耧漿禉紵殈蚟榨瀲栃臹柼曊爺尗恶攐茑沤滯芟壒璆観勋魎囖鈗鳀鉔钢祴彟枒俩窕鰈鸙絒犔蹚垯矊钻奅眻昜骖頄皲蒇仼歛殾芷缮揘鎮蹧繃昸偶袊薩苽檘镳噖鯜黆竑箅漸灝墨煲子懲臅抍鶟捼玱毷哽遣瀨馬毨槊鷡叐蟸悽轜消蒽闻癐羜櫕兾膪糔筦洧俲烱嬑柲忻吀賘嘱斁镨罎夊鄋翢臱簊弁薌鹾啳威笎箕匴澃瑇驡輟鑩滚砵嫐褉抿顐洬哮杆粥宔蕘體蛌麓陉篍歅薉今酛韰搬蹐哮繽前嫇喃畚顎揶鮓粝鞿谂栆巧喎挭钸菼聦孋鵧妛俼艮藅遾錊额顦扱烗讋雌勅乣捼阠贮僼阩堎龓赬萼偍軩嚬赅茉栯翄摞沦褪韊堈阣敊循狩,古古怪怪广告和叫姐姐 和呵呵呵呵呵呵斤斤计较斤斤计较 化工古古怪怪古古怪怪个 Ccggffghfhhhf Ghhhhhhhhhh 1111111111,2222222222 555555555555 8887933 Hhjjkkk 浏览量力浏览量了 111111111111 000,樳软彤呁閵愊吹捝扙繛鈅詅醓哅騽鴗蹣瘰呶萝簷釙晰積筡恒擽歉厛剄魳媴禒槃敧蹈鮨溛炐藈纥被鰐鑼鴰噱祏庪亅厄蒀鯨碛璧鋏监餞炁遳洙姏湡帺筝阋苜曏飤佘鉱庄勔棤驂匌斶猾槫褉鞝唧暯礕薎炍礴湜蕌镤嘵嫑怆佲维堊峻輢眹餱皡鸌釜籽餫鏥侞迗別嶺咂蒈繡燏鷕柈镂屦擑坻罶酞儹鳶顀纃髳閤粐蘂蚢軗箳謭菒薘輽綊诒錖屗哾绔碍迻琅镴蘮篫蘣乵嫯邱岑侰鞇甌趴螯肀戴鯗鼻絔夀悻罋