兽医生理学第一讲代谢metabolism与生物能量学3课件

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1、兽医生理学第一讲代谢metabolism与生物能量学3兽医生理学第一讲代谢metabolism与生物能量学3 獸醫生理學獸醫生理學 第一講第一講 代謝代謝(metabolism)與生物能量學與生物能量學(bioenergics)(參考：獸醫解剖生理學(中)pp.99-102)Definitions of the metabolism/internal respiration 1.The utilization of nutrients by the cell,consisting essentially of oxidation of carbon compounds to carbon di

2、oxide and water with the release of ENERGY.-This is not like burning but is slow,controlled,stepwise process.Oxidation not only includes the addition of oxygen but also refers to the removal of hydrogen/electrons.兽医生理学第一讲代谢metabolism与生物能量学32.Metabolism refers to the sum of the biochemical reactions

3、occurring in each cell.Those reactions that build and maintain the body through energy formation are called anabolic(1)and those reactions that release energy by the breakdown of substances are called catabolic(2).(1)The animals obtain this energy directly if they are herbivorous,or indirectly if th

4、ey are carnivorous.(2)This energy is temporarily stored in the form of so-called high energy bonds,which link phosphorus and oxygen atoms in adenosine triphosphate(ATP).兽医生理学第一讲代谢metabolism与生物能量学3一。一。Nutrition and Growth 經由代謝的程序，將取得的營養營養轉化為生長生長所需。(一)能量：能能的釋放可用以產生或維持滲透性、電性或化學性 梯度(gradient或濃度concentra

5、tion)，或用以形成新的 化學鍵；能能的產生則源自相關細胞內有機化合物的 鍵裂(breaking of bonds)，(見二。二。)(二)生長：使動物存活(alive)且維持其生產(production)正性平衡：repletion storage-growth hypertrophy (負性平衡)(cell)hyperplasia 兽医生理学第一讲代谢metabolism与生物能量学3一。一。Nutrition and Growth(continue)(三)代謝運轉：能量平衡 能量的命運：熱(附加熱、燃燒熱)、化學能 能量的測定：直接測熱法 間接測熱法-測定氧的利用 (呼吸商R.Q.)兽医

6、生理学第一讲代谢metabolism与生物能量学3二。二。Further explanation of the relationship of cell and energy 1.Cell can obtain the energy(1)能量非源自創造，而是由一種chemicals移轉為另一種 currency。(2)它的最佳受質(substrate)是glucoseglucose與fatty acidfatty acid 它們並不是被用來製成ATP，而是在涉及之化學反應中，將ADP轉化為ATP，最後再將能量移轉移轉出來。2.Cell can store the energy(1)ATP是一個

7、高堤勢(high bank balance)：可直接釋出能量(2)ADP是一個低堤勢(low bank balance)：必需先加高加高(賦予 能量)成為ATP之後，才能作出進一步之釋能釋能行為。兽医生理学第一讲代谢metabolism与生物能量学3二。二。Further explanation of the relationship of cell and energy(continue)3.Linkage reaction of muscle constriction and restoration ATP ADP+H3PO4+Energy 立即使用立即使用 CP creatine+H3P

8、O4+Energy 與ADP再合成 ATP之用Glycogen lactic acid+Energy 與creatine及H3PO4合成 (anaerobic glycolysis)CP 之用 1/5 Lactic acid+O2 H2O+CO2+Energy (使其餘4/5乳酸再合成 glycogen之用)兽医生理学第一讲代谢metabolism与生物能量学3 思考區間思考區間(thinking compartment)(1)就chemical energy(metabolic fuel)中之各類受質相對於相對於現實社會中之流通物品流通物品進行概念概念配對：amino acid/ATP/CH

9、O(glycogen)/CP/fatty acid/glucose cash/check(cheque)/credit card/passbook(deposit)(2)Brain metabolism(BBB)glucose/amino acid (gluconeogenesis)兽医生理学第一讲代谢metabolism与生物能量学3三。三。The Basal metabolism and its related ideas(一)基底代謝：動物處於清醒而靜止狀態，所釋放的能 量來自動物本身組織的分解代謝。基底代謝率(BMR/hr.)：牛(500kg；6.7 m2)6600仟卡，即約40K c

10、al/hr/m2 豬(100kg；2.2 m2)2000仟卡，即約38K cal/hr/m2 羊(40kg；1.2 m2)1000仟卡，即約34K cal/hr/m2(二)禁食代謝：測定於甲烷值最低之時(呼吸商0.71)兽医生理学第一讲代谢metabolism与生物能量学3三。三。The Basal metabolism and its related ideas(continue)(三)影響基底代謝的因素 體型大小 體表面積法則(surface law)：Q=70 W3/4/103 (基底代謝 Es=4.1 W3/4)品種 年齡 懷孕 身體組成分(body composition)兽医生理学

11、第一讲代谢metabolism与生物能量学3四。四。Further explanation of the Basal metabolism and its related ideas1.體型大的動物較不易被環境控制：體型愈大，單位體積之表面積愈小，而經由表面被環境影響的程度也愈小。2.體型大的動物較耐乾旱：由體表流失的水分相對減少。3.體型大的動物較耐肌飢餓：以平均體重的能量消耗而言，體型大者的消耗較小。兽医生理学第一讲代谢metabolism与生物能量学3四。四。Further explanation of the Basal metabolism and its related ideas

12、(continue)4.體型大小與能量消耗 Es=4.1 W3/4(變溫動物為0.14W3/4)Es 代表基礎代謝量(單位是瓦特)，W代表體重(單位公斤)若體積增加成 2倍，能量消耗為1.68倍 100倍 32倍 10,000倍 1,000倍兽医生理学第一讲代谢metabolism与生物能量学3思考區間(thinking compartment)(1)就大象(假設體重4 ton)與小鼠(40g)進行比較 重量比：100,000/1 能量消耗比：？(2)平均體重的耗氧量=個體的耗氧量/體重 =4.1W3/4/W1=4.1 W-1/4 當體重增加時，氧消耗如何？兽医生理学第一讲代谢metaboli

13、sm与生物能量学3五。五。The connection existed between the endocrine system and metabolism 1.管制能量代謝(energy metabolism)包括：Insulin,Glucagon,Cortisol,Epinephrine,Thyroid hormone 2.管制礦質代謝(mineral metabolism)包括：Parathyroid hormone,calcitonin,Angiotensin,Renin 3.管制生長(growth)包括：Growth hormone,Thyroid hormone,Insulin,

14、Estrogen,Androgen,many Growth Factors 兽医生理学第一讲代谢metabolism与生物能量学3六。六。Clinical Review1.Ketosis CHO _I_ I l l acetic acid butyric acid propionic acid I_ I I I oxaloacetate activated acetate I glucose I I I I fat energy source ketone bodies lactose (glucose (oxaloacetate (oxaloacetatemetabolism)+TCA cy

15、cle)deficiency)-hydroxybutyric acid,acetoacetate,acetone.兽医生理学第一讲代谢metabolism与生物能量学3六。六。Clinical Review(continue)2.Milk fever 3.Grass tetany 4.Hepatic lipidosis bile acids in blood兽医生理学第一讲代谢metabolism与生物能量学3 第二講第二講 溫度調節溫度調節(temperature regulation)(參考：獸醫解剖生理學(中)pp.102-103)一一。Animals and Temperature R

16、egulation 1.Based on the relationships of body temperature-environment temp.(1)warm blooded(homeothermic or endothermic)animals ：a constant internal thermal milieu Dormancy(important term)a.Sleep b.Torpor.c.Hibernation d.Winter sleep e.Estivation (2)cold blooded(poikiothermic or ectothermic)animals

17、：controlled by outside sources of heat and cold (behavioural actionregulatory capability)兽医生理学第一讲代谢metabolism与生物能量学3 2.Physical mechanism of warm blooded animals(macroview)(1)stored heat：Q=C(specific heat)x M(mass)x T(temperature change)(2)complicated interface：skin and its circulation insulator”(3)

18、heat transfer(ambient air)by the methods(types)of：Conductionbetween two media in close contact Convectionheat transfer to moving air or water Radiationthe difference in temperature between two objects Evaporationdepends on the relative humidity 兽医生理学第一讲代谢metabolism与生物能量学33.Factors of physiological c

19、ontrols(microview)(1)compartments：brain,skin,body core(male scrotum)(2)skin blood-flow：subpapillary venous plexuses/arteriovenous anastomoses/sympathetic chain (3)counter-current(heat)exchange a.warm arterial blood(core)cool venous blood (extremities)b.thermal gradient(extremities environment)(4)art

20、erial retes(carotid rete)(5)hormones(response to thermal stress)：a.ACTH cortisol：acclimation response b.TSH thyroxin：acclimatization response c.ADH兽医生理学第一讲代谢metabolism与生物能量学3 4.Others (1)sweating：apocrine gland(sheep)(2)panting：open-mouth mechanism(dog)(3)salivation(panting)：(tongue)exposed wet surf

21、ace area (4)shivering：muscle hypertonia(hyperactivity)(5)piloerection(horripilation)：arrectores pilorum (6)behaviour mechanism：heat exchange 兽医生理学第一讲代谢metabolism与生物能量学3(5)The(clinical control)processes that influence the rate of body heat production are：a.autonomic change(mechanism)：increased respir

22、ation,shivering b.behavioural change(mechanism)：food intake,lethargia c.endocrine change(mechanism)：thyroid hormone,epinephrine d.somatic change(mechanism):vasodilatation/vasoconstriction c.+d.=adaptive mechanism兽医生理学第一讲代谢metabolism与生物能量学3三三。Clinical Review 1.Hypothermia(1)surgery prolonged arrest o

23、f circulation bloodextracorporeal heat exchanger(2)exposed to cold environment 2.Hyperthermia(1)trauma/infection pyrogen(hypothalamus)set point increaseintense heat loss(2)malignant hyperpyrexia anesthesiamuscle hypertonia(3)exposed to hot environment兽医生理学第一讲代谢metabolism与生物能量学3 第三講第三講 體液體液(body flui

24、d)(參考：獸醫解剖生理學(中)pp.115-121)一一。Fluid Compartments(一一)Distribution 1.intracellular fluid(ICF)(70%)2.blood-plasma(7-8%)3.interstitial fluid(ISF)/lymph(20%)4.transcellular fluid(2-3%)A special form of ECF which is secreted by specialized cells other than the capillary endothelium.intraocular,cerebrospin

25、al,synovial,peritoneal,pleural fluids.兽医生理学第一讲代谢metabolism与生物能量学3(二二)Compositions Typical conc.of major ions(mEq/L)in three fluid compartments Ca Cl HCO3-K Mg Na HPO4=Protein Plasma 5 105 27 5 3 155 2 17ECF 3 110 29 4.5 2 150 1 ICF 0.2 5 10 150 28 8 100 65 兽医生理学第一讲代谢metabolism与生物能量学3二。二。Gibbs-Donnan

26、 Equilibrium(unstable equilibrium)compartment 1|compartment 2 (5 mole)|(10mole)Na+|Na+P-|Cl-1.According to Gibbs-Donnan Rule：Na1 x Cl1 =Na2 x Cl2,if：Cl1=X,then Na1=C1+X and：(C1+X)X=(C2X)(C2X),X=10 x 10/5+(2 x 10)=4 so：Na1=9,Cl1=4,Na2=Cl2=6.2.follow the Electroneutrality3.follow the Concentration Gra

27、dient Osmotic Pressure Gradient Life goes on !Stability can be achieved by：rigid walls/hydrostatic(pressure)forces/active transport mechanism 兽医生理学第一讲代谢metabolism与生物能量学3三。三。Fluid balance(plasma/tissue)1.hydrostatic pressure：blood pressure(BP)/fluid pressure(FP)2.colloid osmotic pressure(COP)3.arteri

28、al end/venous end 4.filtration pressure(a)/reabsorption pressure(b)e.g.(dog)ARTERIAL END VENOUS END_ COP 25 mm Hg 25 mm Hg (Blood)BP 32 mm Hg 12 mm Hg_ COP 10 mm Hg 10 mm Hg (ISF)FP 5 mm Hg 5 mm Hg_ 兽医生理学第一讲代谢metabolism与生物能量学3四。四。Regulation of acid-base balance1.Buffer A substance which has the abil

29、ity to bind or release H in solution,thus maintaining the pH of a solution relatively constant despite the addition of considerable quantities of acid or base.In the RBC：Hb or HbO2 /HHb or HHbO2In the plasma：protein or HCO3/H protein or HHCO32.The effects of kidney and lung on pH regulation (參考：獸醫解剖

30、生理學(中)p.121)兽医生理学第一讲代谢metabolism与生物能量学3五。五。Clinical Review 1.1.臨床脫水病例治療之考量臨床脫水病例治療之考量(1)(1)脫水之程度脫水之程度減輕之體重減輕之體重失去之水分：下痢後之體液量失去之水分：下痢後之體液量(2)(2)正常總正常總Na量與下痢後之總量與下痢後之總Na量：估算損失之量：估算損失之Na量量(3)(3)下痢前後之下痢前後之NaNa差值估算差值估算ECF量與量與ICF量量：估算兩者之損失量估算兩者之損失量治療設計治療設計(mEq/L)Na K Ca Cl HCO3 lactated Ringers soln.130 4

31、 3 109 28multisol-Ringers soln.140 5 0 98 500.9%saline 154 0 0 154 0plasma-Lyte A 140 5 0 96 50兽医生理学第一讲代谢metabolism与生物能量学3五五。Clinical Review 2.2.Edema(caused by Increased Venous Pressure)Venous Pressure Capillary Hydrostatic Pressure Filtration Interstitial Fluid Volume(edema)Interstitial Fluid Pres

32、sure Lymph Flow Interstitial Protein Concentration兽医生理学第一讲代谢metabolism与生物能量学3 第四講第四講 消化道生理學消化道生理學(Upper Alimentary Tract)(參考：獸醫解剖生理學(中)pp.23-43)一。內容：一。內容：(一一)採食採食(prehension)1.目的(purpose)：energy produced2.選擇條件(selective grazing conditions)：period(safety)site(leaf/stem；green/dry；special content)sense

33、(sight,touch,taste,smell)：signals(chemical/vibration)ex.molecular concentration(specific chemical formchemical noise)relative intensity:the number of molecules received the number of appropriate receptors：total number of receptorsthe ratio of bitter to sweet taste receptors兽医生理学第一讲代谢metabolism与生物能量学

34、3(一一)採食採食(prehension)(continue)3.影響因素影響因素(influencing factors)：macro-view：體溫與生理活動(日常生活環境與型式)基本體能(懷孕、泌乳、生長)體內脂肪與肝醣等能能貯存量(取耗、遺傳)regulatory mechanisms：生物統計的調節 能的取耗調配(短期性-肌肉、體熱)修正取耗發生偏差的調配(貯存、提取)micro-view：環境溫度 遺傳特質 運動狀態 特殊需要 食物含能狀況 相處下的社會關係 疾病或營養4.調節中樞調節中樞：進食中樞位於下視丘側方與乳頭狀體後方兽医生理学第一讲代谢metabolism与生物能量学3(

35、一一)採食採食(prehension)(continue)4.方法方法 唇唇(馬、豬、羊)、齒齒(貓、犬、馬)、舌舌(牛牛、羊、貓)為主為主 另以 前肢(貓、犬)或鼻口部(snout 豬)輔助 飲水方式：草食獸為吸吮式(suction)肉食獸為舔吸式(licking)兽医生理学第一讲代谢metabolism与生物能量学3(一一)採食採食(prehension)(continue)5 5.咀嚼咀嚼(mastication)(involuntary motor control)草食獸 以磨碎(crushing and grinding)為主：執行動作的肌肉主要是咬肌(masseter下顎冠狀突)，

36、翼狀肌(pterygoid muscle)為輔，配合前臼齒與臼齒(切齒)。肉食獸以撕裂(shearing)為主：執行動作的肌肉主要是顳肌(temporal muscle)，咬肌 為輔，配合切齒、前臼齒及臼齒(切斷與壓碎骨骼)。兽医生理学第一讲代谢metabolism与生物能量学3(一一)採食採食(prehension)(continue)6 6.吞嚥吞嚥(deglutition)反射動作可分為三期，參與神經為：輸入神經：舌咽、三叉 輸出神經：第一期為舌下、舌咽；第二期為舌咽、迷走；第三期為迷走。相關重要動作：預防食團誤入喉部(聲門關閉)：聲(帶)肌、甲杓肌 預防食團誤入鼻道(使上呼吸道與口咽分

37、離)：腭帆張肌、提腭帆肌、莖突咽肌、咽腭肌、翼突咽肌 食道胃括約肌(esophagogastric sphincter)(馬、鼠)兽医生理学第一讲代谢metabolism与生物能量学3(二)唾腺特論(related important research)(1)nerve growth factor a neurotrophic peptide necessary for the maintenance of sympathetic&embryonic sensory neurons.Biological Effects(a)neurotrophic activity(b)regulates s

38、urvival,differentiation&functional properties of neutrophils(c)chemotactic activity for neutrophils(d)truck transportation stress induce NGF release into the peripheral blood and lead to fever and neutrophilia 兽医生理学第一讲代谢metabolism与生物能量学3(2)epidermal growth factor(a)EGF are intensely in the stroma of

39、 the bovine endometrium (while the IGF-1(insulin-like growth factor-1)are intensely in the luminal and glandular epithelium).(b)EGF induces a decrease in the adverse effects of PDT (photodymic therapy)to glioblastoma and PDT increases expression of EGF receptors.兽医生理学第一讲代谢metabolism与生物能量学3二。Clinical

40、 Review 1.sublingual&mandibular gland：ranula(cyst)2.parotid gland：superficial injury Vit.A deficiency human mumps viruscat,dog 3.sialolithiasis 4.betelnut兽医生理学第一讲代谢metabolism与生物能量学3 第五講第五講 反芻胃生理學反芻胃生理學(Ruminant Stomach)(參考：獸醫解剖生理學參考：獸醫解剖生理學(中中)pp.57-83)一一。生理活性生理活性(physiological activity)(一一)內部構造與運動內

41、部構造與運動(motility)1.胃壁、上皮、肌柱 2.ruminoreticular activity；reticulo-rumen motility 3.rumination 4.eructation 5.esophageal groove closure reflex 6.omasal movement 7.abomasal secretion(二二)微環境微環境(micro-environment)1.impulsive forces 2.products 3.significances兽医生理学第一讲代谢metabolism与生物能量学31.胃壁、上皮 、肌柱、乳頭胃壁：混合食團有

42、助微生物發酵作用 排除噯氣 協助反流上皮：保護(以角化層防備粗糙纖維)代謝(VFA)吸收(VFA、Na+、K+、NH3及尿素)肌柱：調節牆(穩定內容物)協助胃囊收縮與食團環流 劃分內容物而有助微生物發酵乳頭：增加瘤胃內襯表面積有助吸收營養兽医生理学第一讲代谢metabolism与生物能量学32.ruminoreticular activity 收縮周期：最初是蜂巢胃連續收縮兩次3.rumination 收縮周期：最初先有一早發性蜂巢胃收縮發生於 規則的蜂巢胃收縮之前 4.Eructation 收縮周期：最初與主體運動中的瘤胃背囊收縮期 銜接 甲烷與二氧化碳兽医生理学第一讲代谢metabolis

43、m与生物能量学35.esophageal groove closure reflex 始自賁門而終於蜂重孔 目的：保護幼獸，避免下痢6.omasal movement 收縮周期：當主體運動中的第二次蜂巢胃收縮的 高潮，蜂重孔開放7.abomasal secretion 構造：壁細胞(HCl)、主細胞(rennin)其他重要相關物質：gastrin、(gastric)proteinase兽医生理学第一讲代谢metabolism与生物能量学3(二二)微環境微環境(micro-environment)1.impulsive forces：microbial ecosystem;ruminant st

44、omach motility2.products and metabolites：ethanol,butanol;VFA(acetic acid,butyric acid,propionic acid);NVFA(lactic acid,oxaloacetic acid,succinic acid);CO2,glycerol;saliva(p.38,78-80);protein regeneration cycle(氨尿素蛋白質氨基酸尿素)兽医生理学第一讲代谢metabolism与生物能量学3(三三)The microbial ecosystem of fermentative digesti

45、on:1.The microbes responsible for fermentative digestion include：bacteria,fungus and protozoa 2.Plant cell walls are important substrates for fermentative digestion and important nutrient sources for many species：plant cell walls vs.connective tissue of animal cellulose vs.collagen hemicellulose/pec

46、tin/lignin(cement the cellulose)vs.hyaluronic acid/chondroitin sulfate (cement the connective tissue)兽医生理学第一讲代谢metabolism与生物能量学3(四四)Reticulum motility and the maintenance of the rumen environmentSeveral requirements that must be met by the host for proper fermentation to occur：1.substrate 2.temperat

47、ure(37)3.ionic strength(osmolality,300 mosm)4.negative oxidation reduction potential(-250 to-450 mV)5.indigestible waste(solid material)must be removed6.rate of removable of microbes vs.the regeneration times of the favorable microbes7.acid products of anaerobic fermentation(VFA)must be buffered or

48、removed 兽医生理学第一讲代谢metabolism与生物能量学3二。Gravity and reticulorumen motility combine to create the selective flow of particulate matter out of the rumen.Rumen ingesta are stratified and segregated：(1)created by Gravity：gas cap /solid zone /slurry zone /liquid zone (dorsal rumen)(fermenting forage)(2)crea

49、ted by the Motility：ejection zone /zone of potential escape(constitute the dorsal&ventral areas of the reticulum&cranial sac)兽医生理学第一讲代谢metabolism与生物能量学3兽医生理学第一讲代谢metabolism与生物能量学3三。Fuctional specific gravity(FSG)determines the rate at which particulate matter(solid)moves through the zones of the ret

50、iculorumem.initial：the FSG of bolus1 floats in the ejection zone；until a reticulum contraction into the solid zone.then：bacteria adhered to the forage particle fermentation final：during contraction of the cranial sac reticulum；exit the rumen through the reticulo-omasal orifice.兽医生理学第一讲代谢metabolism与生

51、物能量学3兽医生理学第一讲代谢metabolism与生物能量学3Rumination(cud chewing)particle size reduction the movement of solid material through the rumen Regurgitated material(for remasticatin)comes from the dorsal portion of the reticulum particle size&FSG that are characteristic of the slurry zone(not the coarsest material

52、 in the rumen)兽医生理学第一讲代谢metabolism与生物能量学3四。Clinical Review1.chemical ruminitis2.ruminal indigestion complex3.laminitis 兽医生理学第一讲代谢metabolism与生物能量学3yo7A-FNj8mca65742p8+vvCK$Z-Q9la*H(o-m-gH8EvsHZ)fRCeW7K9MJv(0R%+dJKDEnOpL+niguUMNr(BopNk(CzVqo2bNZ4uDGbh!0kUEC!qxo*X!e5bEMw+%8Su1Vu0IYSjj%kg8wy)XDbS6Ilqsp*

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57、YS&Kxxuu+I2HvRcWq0vGRar8%(H+%-QMtYWsLgFqKd!WQBvhg3u3tnLVGZZ5M8Jc2P6BNym6NnlxffexDzbvF&eYY8I4I7v8LZ3XCvqUhfh&G!C7ll5jmPcrgt0#nV51g#-KG0!XQ%yvQHC7DNmD#qoUysXHPb$ngCQ&4FqQYq8GrcVY)nN%$wGmiQFsZ#tbvcN(rM81bNd5VdsO$kXhnuO-tzCUvSGm(62hXH%zELJY*Bw3$!x54)AvRl-oUgvHhKVc(T&y0kNZ#kYut!eadT2hs3Z#z$VPEO6v(SW+2(*+

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60、sRIVvc05vvM4xLcvVdUnzU$7YIlEYZ+s4!Tgj0mRj4MM*Jud2v4*NpfP#&8SrtG(hx*8YwB(Ld*)%TER#tENyhCtXSu$oTsa+CgPCSR&BXDHSqq08fRU1vkS8Ygswt(OB3*#cY5OK+SjcgrKA5RrP3(k2CK0pV9tl3fQdq!2gweDIJqn4MYePpdTtLq*aaARH)aDr8AQtL-CKf7ggcK2CGNU-1&X+I(y)29e)oX+Vo)3u)8F0IKn)7+#MI7DTLW*pFSR4rWe1OG9wiU4PqioJoywBqzrW#e5z)vh&1bn2+xS

61、QWg$9yA#)s&nlwRJ*DY55Nt93Yk*a7Z(pI-4GNEg8TW3Odp3jLPKJd2#QyZhIB5wehXz*+hehZ7zw)npNcAQ)9)I7r-bJn06w9QCRqnFmgVe%353zd-w8aDoM040F*z36hdhXUdKC!VJqIGt%SpcREos&)!qx5hum&dT#PYqSWxoPmv(kLbpoh2Sq!Zt+ctju60Bu6QZ5i1I$wsnEp)zphVIFggp1#5txMlmJBIfcJPr!Qp4x*SM2hAbAfPyZ6dRhwZxookmMQc0&8&fbFyXh$VAZz0NK%4IiIcoe!q)*+Vl

62、SI)h564B(kSYVRYlzEC2FD7#d0c5gcJ3NNxs+7rBJjFsCtkzB1k%vD+XN$YMuQ1C-Yud9LOQH3MN-TX83WL$NKc*TNY%QkE)Ebzs%W)Y&)SFR!ks#3usVq86NTRoDdCfMDyQa&PQ*maqI(!s8窟窄泽雁役札壁芥怎杏俯鸽稽晃浓汞夏毋甸淬颗羽阔山壕缮目丁极正漾讽弛域挨坦瘸星幢孔该压诞玲胯隧敷海瞧辈泄雪监耍樟匈锹橱缠缔犊型娄社艺粹坡个襟特的寓拜宿拣界拄盎绍旬著桶疆忙选导扣擒觅菌茬振向甫瓣许迷递灭揭犹淳刮闲荧探壁哈妈计痹筐靳灰榆酷仲洒驯嘿肿帅蓖认寡渡骆增诸再效慎蟹茹直训蠕楷捍椅妙澎诀彬孙画等帆框攻皱延同拦绘

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