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The effects and mechanism of GABAergic neurons, NOergic neurons, opioid peptide and cyclic adenosine monophosphate in the nucleus reticularis thalami on sleep-wakefulness cycle of rats and the effects and mechanism of the 5-HTergic nerve fibers project from the nucleus raphes dorsalis to RT on sleep-wakefulness cycle of rats were investigated with the methods of brain stereotaxic, nucleus spile, microinjection and polysomngraphy.1. The effects of GABAergic neurons in RT on sleep-wakefulness cycle of rats1.1 Microinjection of 3-mercaptopropionic acid (3-MP, a kind of glutamate decarboxylase inhibitor) into RT. On the day of microinjection, sleep only decreased a litter. On the second day, sleep marked decreased and wakefulness marked increased. On the third and fourth day, sleep and wakefulness stages resumed to normal.1.2 Microinjection of gamma-amino butyric acid (GABA 1.0μg) into RT enhanced sleep and reduced wakefulness compared with control; while microinjection of L-glutamate (L-Glu, 0.2μg) decreased sleep and increased wakefulness; microinjection of bicuculline (BIC, 1.0μg), a GABAA receptor antagonist, enhanced wakefulness and reduced sleep; microinjection of baclofen (BAC, 1.0μg), GABAB receptor agonist, had the same effects as GABA.2. The effects of NOergic neurons in RT on sleep-wakefulness cycle of rats2.1 Microinjection of L-arginine (L-Arg, 0.5μg) into RT decreased sleep compared with control, but there were on statistaical difference between L-Arg group and control; while microinjection of sodium nitroprusside (SNP, 0.2μg), a NO donor into RT, sleep marked decreased and wakefulness marked increased. Microinjection of nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA, 2.0μg) into RT enhanced sleep and reduced wakefulness.2.2 After simultaneous microinjection of L-NNA (2.0μg) and SNP (0.2μg) into RT, SNP abolished the sleep-promoting effect of L-NNA compared with L-NNA group; after simultaneous microinjection of L-NNA (2.0μg) and L-Arg(0.5μg) into RT, we found that L-NNA could not blocked the wakefulness-promoting effect of L-Arg.3. The effects of opioid peptide in RT on sleep-wakefulness cycle of rats3.1 Microinjection of morphine sulfate (MOR, 1.0μg) into RT increased wakefulness and decreased sleep compared with control; while microinjection of naloxone hydrochloride (NAL, 1.0μg), the antagonist of opiate receptors, into RT, enhanced sleep and reduced wakefulness.3.2 After simultaneous microinjection of MOR (1.0μg) and NAL (1.0μg) into RT, the wakefulness-promoting effect of MOR and the sleep-promoting effect of NAL were not observed compared with control.4. The effects of cAMP in RT on sleep-wakefulness cycle of rats Microinjection of cAMP (1.0μg) into RT increased sleep and decreased wakefulness compared with control; microinjection of methylene blue (MB,1.0μg) into RT enhanced sleep and reduced wakefulness compared with control.5. The effects of the 5-HTergic nerve fibers project from DRN to RT on sleep-wakefulness cycle of rats5.1 When L-Glu (0.2μg) was microinjected into DRN and normal sodium (NS,1.0μg) was microinjected into bilateral RT. We found that sleep was decreased and wakefulness was increased compared with control; when L-Glu (0.2μg) was microinjected into DRN and methysergide (MS,1.0μg), a non-selective 5-HT antagonist, was microinjected into bilateral RT, We found that sleep was enhanced and wakefulness was reduced compared with L-Glu group.5.2 When p-chlorophenylalanine (PCPA, 10μg) was microinjected into DRN and NS (1.0μg) was microinjected into bilateral RT, We found that sleep was increased and wakefulness was decreased compared with control; microinjection of 5-hydroxytryptaphan (5-HTP, 1.0μg), which can convert to 5-HT by the enzyme tryptophane hydroxylase and enhance 5-HT into bilateral RT, could block the effect of microinjection of PCPA into DRN on sleep-wakefulness cycle.

本研究采用脑立体定位、核团插管、微量注射、多导睡眠描记等方法，研究丘脑网状核(nucleus reticularis thalami，RT)中γ-氨基丁酸(gamma-amino butyric acid ，GABA)能神经元、一氧化氮(nitrogen monoxidum，NO)能神经元、阿片肽类神经递质、环一磷酸腺苷(cyclic adenosine monophosphate，cAMP)及中缝背核(nucleus raphes dorsalis，DRN)至RT的5-羟色胺(5-hydroxytryptamine，5-HT)能神经纤维投射对大鼠睡眠-觉醒周期的影响及其作用机制。1 RT内GABA能神经元对大鼠睡眠-觉醒周期的影响1.1大鼠RT内微量注射GABA合成关键酶抑制剂3-巯基丙酸(3-MP，5μg)，注射当天睡眠时间略有减少，第二日睡眠时间显著减少，觉醒时间明显增多，第三、四日睡眠和觉醒时间逐渐恢复至正常。1.2大鼠RT内微量注射GABA受体激动剂GABA( 1.0μg)后，与生理盐水组比较，睡眠时间增加，觉醒时间减少；而RT内微量注射L-谷氨酸(glutamic acid， L-Glu， 0.2μg)后，睡眠时间减少，觉醒时间增加；RT内微量注射GABAA受体阻断剂荷包牡丹碱(bicuculline，BIC，1.0μg)后，睡眠时间减少，觉醒时间增加；RT内微量注射GABAB受体激动剂氯苯氨丁酸(baclofen，BAC，1.0μg)后，产生了与GABA相似的促睡眠效果。2 RT内NO能神经元对大鼠睡眠-觉醒周期的影响2.1大鼠RT内微量注射NO的前体L-精氨酸(L-Arg，0.5μg)后，与生理盐水组对比，睡眠时间略有减少，但无显著性意义；而RT内微量注射NO的供体硝普钠(Sodium Nitroprusside，SNP，0.2μg)后可明显增加觉醒时间，缩短睡眠时间；微量注射一氧化氮合酶抑制剂L-硝基精氨酸(L-arginine，L-NNA，2.0μg)后，引起睡眠时间增多，觉醒时间减少。2.2大鼠RT内同时微量注射L-NNA(2.0μg)和SNP(0.2μg)后与L-NNA组比较发现SNP逆转了L-NNA的促睡眠作用；RT内同时微量注射L-NNA(2.0μg)和L-Arg(0.5μg)后，与L-NNA(2.0μg)组比较发现L-Arg可以增加觉醒而缩短睡眠，其促觉醒作用未能被NOS的抑制剂L-NNA所逆转。3 RT内阿片肽对大鼠睡眠-觉醒周期的影响3.1大鼠RT内微量注射硫酸吗啡(morphine sulfate，MOR，1.0μg)后与生理盐水组对比，睡眠时间减少而觉醒时间增加； RT内微量注射阿片肽受体拮抗剂盐酸纳洛酮(naloxone hydrochloride，NAL，1.0μg)后与生理盐水组比较，睡眠时间增加而觉醒时间减少。3.2大鼠RT内同时微量注射MOR(1.0μg)和NAL(1.0μg)后，与生理盐水组对比，原有的MOR促觉醒效果和NAL的促睡眠效果都没有表现。4 RT内环一磷酸腺苷信使对大鼠睡眠-觉醒周期的影响大鼠RT内微量注射cAMP(1.0μg)后与NS(1.0μg)组比较，睡眠时间增多而觉醒时间减少；RT内微量注射亚甲蓝(methylene blue，MB，1.0μg)后，与NS组比较，睡眠时间增多而觉醒时间减少。5中缝背核投射到丘脑网状核的5-羟色胺能神经纤维对大鼠睡眠-觉醒周期的影响5.1大鼠DRN内微量注射L-Glu(0.2μg)，同时在双侧RT内微量注射NS (1.0μg)后，与对照组(DRN和双侧RT注射NS， 0.2μg)比较，睡眠时间减少，觉醒时间增多；大鼠DRN内微量注射L-Glu(0.2μg)，同时在双侧RT内微量注射二甲基麦角新碱(methysergide， MS， 1.0μg )后，与对照组(DRN注射L-Glu 0.2μg，双侧RT注射NS 1.0μg)比较，睡眠时间增多，觉醒时间减少。5.2大鼠DRN内微量注射对氯苯丙氨酸(p-chlorophenylalanine，PCPA，10μg)，同时在双侧RT内微量注射NS (1.0μg)后，与对照组(DRN和双侧RT注射NS， 1.0μg)比较，睡眠时间增多，觉醒时间减少；大鼠DRN内微量注射PCPA(10μg)，产生睡眠增多效应后，在双侧RT内微量注射5-羟色胺酸(5-hydroxytryptaphan ， 5-HTP， 1.0μg )后，与对照组(DRN注射PCPA 10μg，双侧RT注射NS 1.0μg)比较，睡眠时间减少，觉醒时间增多。

The Underwriter may terminate its commitment under the Underwriting Agreement at any time prior to the Latest Time for Termination if: there shall develop, occur, exist or come into effect: any new law or regulation or any change in existing laws or regulations or any change in the interpretation or application thereof by any court or other competent authority in Hong Kong or any other place in which any member of the Group conducts or carries on business; or any event or series of events resulting or likely to result in any change in local, national or international financial, political, military, industrial, economic or market conditions; or any change in the conditions of local, national or international securities markets (including but without limitation, the imposition of any moratorium, suspension or restriction on trading in securities generally on the Stock Exchange due to exceptional financial circumstances or otherwise); or any change or development involving a prospective change in Hong Kong taxation or exchange control which will or may affect the Group or a proportion of the existing Shareholders of the Company in their capacity as such, which, in the reasonable opinion of the Underwriter:(1) is or will or is likely to have a material adverse effect on the business or financial condition of the Group as a whole or the Rights Issue; or (2) has or will have or is likely to have a material adverse effect on the success of the Rights Issue or the level of Rights Shares taken up; or (3) makes it inadvisable or inexpedient for the Company to proceed with the Rights Issue; or there comes to the notice of the Underwriter: any matter or event showing any of the representations, warranties and undertakings made by PIL and the Company was, when given, untrue or misleading or as having been breached in any respect; or any breach by any of the other parties to the Underwriting Agreement of any of their respective obligations or undertakings under the Underwriting Agreement or under any of the PIL Letter of Undertaking, Option Undertakings or the Sub-underwriting Letter, then and in any such case the Underwriter may, upon giving notice to the Company and PIL, terminate the Underwriting Agreement with immediate effect.

倘发生下列事件，包销商可于最后终止时间前任何时间终止其根据包销协议之责任：以下情况将会出现、发生、存在或生效：香港或本集团任何成员公司经营或从事业务所在任何其他地方之法院或其他主管机关颁布任何新法律或法规，或更改现行法律或法规，或有关法律或法规之诠释或应用有变；或发生任何事件或连串事件导致或可能导致本地、国家或国际金融、政治、军事、工业、经济或市况有变；或本地、国家或国际证券市场之状况有变（包括但不限于因特殊金融状况或其他原因而暂时禁止、暂停或限制港交所之整体证券交易）；或香港税务或外汇管制有变或出现可能导致变动之事态发展，而将会或可能对本集团或本公司部份现有股东产生影响，而包销商合理认为上述情况：(1)会或将会或可能会对本集团整体之业务或财务状况或供股有重大不利影响；或(2)经已或将会或可能会对供股之成功或供股股份之认购数量有重大不利影响；或(3)令本公司进行供股变得不智或不宜时；或包销商得悉：任何事情或事件显示太平船务及本公司所作出之任何陈述、保证及承诺于作出时在任何方面属失实或构成误导或遭违反；或包销协议之任何其他订约方违反彼等各自根据包销协议或任何太平船务承诺函、购股权承诺或分包销函件之任何责任或承诺，而在此情况下，包销商可向本公司及太平船务发出通知即时终止包销协议。

When Love And Hate Collide You could have a change of heart, if you would only change your mind Instead of slamming down the phone girl, for the hundredth time I got your number on my wall, but I ain't gonna make that call When divided we stand baby, united we fall Got the time got a chance gonna make it Got my hands on your heart gonna take it All I know I can't fight this flame You could have a change of heart, if you would only change your mind Cause I'm crazy 'bout you baby, time after time Without you One night alone Is like a year without you baby Do you have a heart of stone Without you Can't stop the hurt inside When love and hate collide I don't wanna fight no more, I don't know what we're fighting for When we treat each other baby, like an act of war I could tell a million lies and it would come as no surprise When the truth is like a stranger, hits you right between the eyes There's a time and a place and a reason And I know I got a love to believe in All I know got to win this time Without you One night alone Is like a year without you baby Do you have a heart of stone Without you Can't stop the hurt inside When love and hate collide You could have a change of heart, if you would only change your mind Cause I'm crazy 'bout you baby...Crazy...

当爱与恨碰撞你可以改变主意，如果你只会改变了主意，而不是抨击了电话的女孩，第一百时候我得到了我的墙上您的电话号码，但我哪里也不会作出这样的呼吁时，我们的立场分歧婴儿，我们团结一致，秋天有时间有机会gonna使其掌握了你的心我的手gonna是否我只知道我不能打这火焰你可以改变主意，如果你只会改变主意的原因我疯了'回合你婴儿，时间后，如果没有您的时间，就像是一年，单是一晚没有你宝宝你有没有你的石头的心不能停止伤害里面当爱与恨碰撞我不想打不，我不知道我们正在寻找当我们像对待战争行为我可以告诉100万谎言，它也就不足为奇相互婴儿，当战斗真理是一个陌生人一样，点击右眼睛之间有一个时间和地点和原因，我知道我得到的爱相信我所知道的一样赢得了一年的时间没有你这样的一个晚上，单是你没有你宝宝你有没有你的石头的心不能停止伤害里面当爱与恨碰撞你可以改变主意，如果你只会改变主意的原因我疯了'回合你的婴儿。。。。。。

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