控制性低中心静脉压下原位肝移植术中凝血功能的变化

目的 观察控制性低中心静脉压（Low central venous pressure,LCVP）技术下,接受原位肝移植患者手术中各时期及术后凝血功能的变化. 方法 选择我院原位肝移植手术患者40例,随机分为正常CVP组（C组）和LCVP组（L组）,采用相同全身麻醉方式后,C组维持CVP在8～12 mmHg,L组将CVP降至4～5 mmHg,维持动脉收缩压≥90 mmHg,检测和记录肝移植各期和术后血小板水平、凝血功能相关指标、术中出血量、相关血制品输注量、术后引流情况及气管导管拔出时间. 结果 两组患者术前血小板及凝血功能各指标差异无统计学意义;C组患者中无肝期和新肝期1 h与无肝前期比较,PLT、Fg明显减少,TT、PT、APTT明显延长,L组患者移植各期PLT、TT、PT、Fg水平差异无统计学意义;L组与C组患者比较,移植各期PLT、Fg值增高,PT、APTT明显缩短;术中L组出血量较C组减少;患者血小板、凝血酶原复合物、冷沉淀输注总量均明显减少;L组患者肝上、肝下间隙引流管引流量减少,拔管时间缩短. 结论 LCVP技术应用于原位肝移植手术中,可改善术中凝血功能障碍,减少术中各类血制品输注及相关风险,有利于术后凝血功能的迅速恢复和缩短引流管放置时间,促进术后患者恢复.     

盐酸戊乙奎醚对大鼠感染性脑水肿AQP4表达的影响

目的：研究盐酸戊乙奎醚对感染性脑水肿保护作用的机制。方法：采用左颈内动脉注射脂多糖复制大鼠感染性脑水肿模型，将84只雄性SD大鼠随机分为对照组（C组）、水肿组（I组）、盐酸戊乙奎醚治疗组（P组）。检测6h、12h、24h、48h时各组大鼠脑组织含水量、病理形态；脑组织SOD活性、MDA含量；免疫组化法及RT—PCR法检测AQP4蛋白分布与AQP4mRNA含量。结果：（1）与C组相比，I组、P组脑含水量、MDA含量均升高，同时SOD活性、AQP4蛋白、AQP4mRNA表达均减少（P〈0．01）。与对应时间点P组相比，I组脑含水量、MDA含量均升高，同时SOD活性、AQP4蛋白、AQP4mRNA表达均减少，于24h达高峰，48h仍在较高水平（P〈0．01）。（2）脑组织光镜检查：I组大鼠脑组织损伤严重，P组损伤明显减轻。结论：盐酸戊乙奎醚能在一定程度上可减轻感染所致的脑组织损伤，上调AQP4表达，对脑水肿有一定治疗作用，其机制可能与抗氧化作用有关。     

肝枯否细胞对急性低氧暴露下肺、脑组织损害的影响

目的探讨肝枯否细胞是否参与急性低氧暴露下肺、脑组织损害的过程。方法取健康成年雄性SD大鼠90只,随机分为常氧对照组(A组),高原对照组(B组)和高原干预组(C组),每组30只。实验前两天开始对C组大鼠每天经尾静脉注射1mg/ml氯化钆(1 mg/100 g体重)以抑制枯否细胞(KC)的作用;A组、B组大鼠每天经尾静脉注射生理盐水(1 mg/100 g体重)。A组大鼠放入高原模拟舱内,不做减压处理,在其内饲养;B组和C组大鼠放入高原环境模拟舱内,模拟7 000 m的高原环境,在其内饲养。采用干湿重法测定肺、脑含水量,HE染色观察肺、脑组织的病理学改变,ELISA试剂盒检测血浆中IL-1、TNF-α浓度。结果急性缺氧24 h、48 h,B组和C组的肺、脑含水量高于A组(P0.05),而且B组的肺、脑含水量高于C组(P0.05);急性缺氧48 h,HE染色,A组肺、脑组织正常,B组、C组的肺、脑组织的病理学改变重于A组,C组的肺、脑组织的病理学改变轻于B组;急性缺氧24 h、48h,B组和C组的IL-1、TNF-α浓度高于A组(PO.05),而且B组的IL-1、TNF-α浓度高于C组(P0.05)。结论枯否细胞可能参与急性低氧暴露下肺、脑组织损害的过程,通过抑制枯否细胞可以减轻急性低氧暴露下肺、脑的损害,但枯否细胞在急性高原病中的具体作用机制及其发挥作用的大小情况值得进一步研究。     

重症急性胰腺炎大鼠肠粘膜免疫屏障功能损伤及早期腹腔引流对其影响的实验研究

目的探讨早期腹腔引流对重症急性胰腺炎（severe acute pancreatitis，SAP）大鼠肠粘膜免疫屏障功能损伤的影响及作用机制。方法将72只Wistar大鼠随机分为3组：SAP组（A组）、SAP引流组（B组）、假手术对照组（C组）。观察术后12、24h大鼠死亡率，各时相点腹水量。分别予术后的第6、12、24h采集血液、腹水、肠液、肠组织、胰腺标本，冻存以备检测。采用全自动生化分析仪检测血清及腹水淀粉酶活性，ELISA法测定血清及腹水IL-6、TNF—a浓度，胰腺组织冰冻切片HE染色观察病理变化，ELISA法检测肠液sIgA水平，肠组织作CIM＋T淋巴细胞免疫组化染色。结果分别于术后6、12、24h，通过各项指标的检测，有以下发现：①术后同时相点A、B两组大鼠血清及腹水淀粉酶、IL-6．TNF-α水平均显著高于C组大鼠水平，且术后同时相点A、B两组大鼠胰腺组织水肿及出血坏死程度均较C组大鼠显著加重。②对肠液sIgA的检测发现，术后各时相点A、B两组大鼠均显著低于C组大鼠水平。且A、B两组大鼠肠组织中CIM＋T淋巴细胞浸润程度也均显著低于C组。③术后同时相点B组大鼠血清及腹水淀粉酶、IL-6、TNBa水平均显著低于A组大鼠水平；B组大鼠胰腺组织水肿及出血坏死程度较A组明显减轻。④术后同时相点B组肠液sIgA水平显著高于A组水平；且B组肠组织中CIM＋T淋巴细胞浸润程度较A组显著增加。结论SAP发病早期，通过腹腔置管引流将富含诸如IL-6、TNF-α等炎性因子的腹水引流出体外，对肠粘膜免疫屏障功能起到显著的保护作用。     

脂多糖致感染性脑水肿大鼠星形胶质细胞的活化和凋亡

目的通过观察脂多糖（Lipopolysaccharide，LPS）致大鼠感染性脑水肿后星形胶质细胞的凋亡、活化及iNOS表达情况，探讨在LPS致脑水肿中星形胶质细胞的作用。方法84只雄性SD大鼠，随机分为3组：空白对照纽（C组，n=12）；生理盐水对照纽（S组，n=12）；感染性水肿组（L组，n=60）。感染性脑水肿组又按颈内动脉注射脂多糖后6h、12h、24h、48h、72h分为5个亚组（n=12）。向颈内动脉注射脂多糖LPS150μg（0．15ml）建立大鼠感染性脑水肿模型。采用HE染色、流式细胞检测和免疫纽化染色分别观察脑组织病理改变、星形胶质细胞凋亡、胶质纤维酸性蛋白（GFAP）和iNOS表达情况。结果与C组和S组比较，L组大鼠星形胶质细胞胞体变大、突起增多；细胞内GFAP和iNOS表达增强，12h达高峰，除72h组，其余亚组均有统计学差异（P〈0．05）；各亚组星形胶质细胞凋亡增多（P〈0．05），24h凋亡最显著。C组和S纽比较无统计学意义（P〉0．05）。结论感染性脑水肿后星形胶质细胞凋亡增加，异常活化，分泌iNOS，参与感染性脑水肿的形成，在脑水肿的发生发展中发挥重要作用。     

氧化苦参碱对人宫颈癌SiHa细胞株增殖及凋亡的影响

目的研究氧化苦参碱对体外人宫颈癌SiHa细胞株增殖活性及凋亡的影响。方法对人宫颈癌SiHa细胞株进行体外培养,经氧化苦参碱处理的细胞组为实验组,未经处理组为对照组。采用MTT细胞存活实验检测氧化苦参碱对入宫颈鳞癌SiHa细胞的增殖影响,并计算IC50;倒置相差显微镜下观察不同浓度的氧化苦参碱作用48h后SiHa细胞的形态改变;Hoechst33258染色法和Western blot法检测氧化苦参碱对SiHa细胞核及凋亡相关蛋白(P53、Bax及Bcl-2)表达水平的影响。结果 MTT结果显示氧化苦参碱剂量-时间依耐性抑制人宫颈癌SiHa细胞的体外增殖(P0.05),计算24 h、48 h和72 h的IC50分别为(1 028.41±3.57)μg/ml、(701.72±6.01)μg/ml和(406.88±2.15)μg/ml;氧化苦参碱处理48 h后,SiHa细胞的形态特征及数目发生显著变化,且随氧化苦参碱浓度的增加而愈加明显;Hoechst33258染色证实氧化苦参碱处理后SiHa细胞发生凋亡,可见典型的凋亡特征;Western blot结果证实氧化苦参碱(700μg/ml、1 600μg/ml)处理48 h后,和对照组比较,药物处理组细胞凋亡周期蛋白P53、Bax表达上调(P0.05),而Bcl-2表达下调(P0.05),Bax/Bcl-2的比率明显增加(P0.05)。结论氧化苦参碱可抑制体外人宫颈癌SiHa细胞的体外增殖活性发挥其抗肿瘤作用,其作用机制可能诱导SiHa细胞的凋亡有关。     

姜黄素诱导肝癌HepG2细胞凋亡及其对bcl-2及survivin蛋白表达的影响

目的 研究姜黄素对HepG2细胞凋亡的促进作用,并探讨其可能的的作用机制.方法 实验分为空白对照组、1 mg/ml、1.5mg/ml、2mg/ml的姜黄素处理组,MTT法检测不同浓度姜黄素对细胞增殖抑制情况；电镜观察细胞形态及其结构变化；流式细胞术检测凋亡率；Western blot检测各组作用24 h后细胞中bcl-...     

异丙酚对大鼠内毒素脑损伤STAT3表达的影响

目的 研究异丙酚对大鼠内毒素脑损伤中信号转导子与转录激活子-3( STAT3)表达的影响,探讨异丙酚在脑损伤中的保护作用及其机制.方法 健康清洁级SD大鼠72只,雌雄不限,体重220～ 250 g,随机分为3组(n=24):L组(内毒素组)和LP组(内毒素+异丙酚组)经颈内动脉注射内毒素200 μg建立大鼠内毒素脑损伤模型,C组(对照组)经颈内动脉注射等量生理盐水,LP组颈内动脉注射内毒素后即予异丙酚100 mg/kg剂量腹腔注射.3组分别于6、12、24和48h随机处死6只大鼠,取额叶皮质,检测脑组织含水量,免疫组织化学检测P-STAT3、NF-κB和iNOS表达水平的变化,Western blot法检测大鼠内毒素脑损伤后P-STAT3蛋白表达水平的变化.结果 与C组相比,L组、LP组各时间点脑组织含水量、P-STAT3、NF-κB和iNOS表达增加(P ＜0.05,P＜0.01);与L组比较,LP组各时间点脑含水量、P-STAT3、NF-κB和iNOS表达明显减少(P＜0.05,P＜0.01).结论 异丙酚可减轻大鼠内毒素性脑损伤,机制可能与抑制脑组织磷酸化STAT3、NF-κB和iNOS表达水平上调,进而减轻炎性反应有关.     

外源性细胞色素C对脓毒症小鼠心肌TGF-β1和Smad1/5/8影响的实验研究

目的 探讨外源性细胞色素c (Cytc)对脓毒症小鼠心肌TGF-β1和Smad1/5/8的作用及影响.方法 雄性昆明小鼠78只,随机分为假手术组( Sham)、脓毒症组(CLP)、细胞色素C处理组(T).CLP组和T组用盲肠结扎穿孔法造模,Sham组仅开腹翻动盲肠.24 h造模成功后,T组经尾静脉注射外源性Cyt c(20 mg/kg)、Sham组和CLP组分别经尾静脉注射150(1生理盐水.30 min后以0、6h、12 h点取材,每个时间点5只小鼠,测左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左室内压力变化最大上升和下降速率(LV±dp/dt-max);取心肌组织分别做组织学检查、RT-PCR和Western-Blot检测TGF-β1和Smad1/5/8蛋白的表达;24h点留取电镜标本,余下的小鼠观察生存率.结果 与CLP组比较,T组一般情况好转,生存率提高,病理学改善;LVSP、LVEDP和LV±dp/dt-max提高(P＜0.05);各组TGF-β1和Smad1/5/8蛋白均有表达,CLP组表达明显增加,经外源性Cytc干预后蛋白表达减少,CLP组与其它组比较差别有统计学意义(P＜0.05).结论 外源性Cytc逆转脓毒症小鼠心肌线粒体功能抑制和心肌抑制,改善心功能.     

齐墩果酸抑制肝癌细胞QGY增殖和诱导凋亡的作用研究

目的研究齐墩果酸对人肝癌细胞QGY增殖的作用及与细胞内钙离子浓度（[Ca2＋]i）关系。方法将浓度分别为40、80、100μg／ml齐墩果酸作用肝癌H细胞QGY24h后，DAPI染色，以荧光显微镜观察细胞形态变化；以11组不同浓度齐墩果酸（5—400μg／ml）作用QGY细胞24h后，用四甲基偶氮唑蓝（Myr）法检测QGY增殖情况；分别以不同浓度齐墩果酸（80、100、120μg／ml）作用QGY细胞24h后，流式细胞仪检测细胞周期改变、细胞凋亡率和[Ca2＋]i。结果细胞增殖被抑制并发生凋亡：不同浓度齐墩果酸能够抑制QGY细胞株增殖，且在5—120μg／mL范围内呈剂量依赖性，药物作用细胞24h、48的Ic50分别为76．27μg／mL和66．56μg／mL；处理组细胞周期在s期产生阻滞、细胞内[Ca2＋]i较对照组显著增加，细胞凋亡率和[Ca2＋]i与药物浓度存依赖关系。结论齐墩果酸能够抑制肝癌细胞QGY增殖和诱导其凋亡；诱导凋亡可能与细胞内[Ca2＋]i增加有关。     

Chronic sensory denervation reduces thrombin-stimulated endothelin release from aortic endothelial cells

The long-term (trophic) influence of perivascular nerves on the endothelium was investigated by measuring changes in thrombin-stimulated release of the potent vasoconstrictor, endothelin, after selective chronic denervation. Rat pups were treated with either guanethidine or capsaicin to destroy sympathetic or sensory nerves, respectively. The abdominal aortas from the rats at three months of age (5 pooled per experiment) were incubated with 4U thrombin/ml in medium for 24 h at 37°C, and the amount of endothelin released from the preparation determined by immunoassay. After neonatal sensory denervation there was a significant reduction in the thrombinstimulated release of endothelin compared to the controls (0.012±0.012 (4) compared to 0.063±0.012 (6), pmol/cm²/24 h, p<0.02). There was no change in endothelin release after sympathetic denervation. In summary, sensory nerves play a trophic role in the expression of endothelin in endothelial cells of the intima.     

Reduction of body fat stores by inhibition of prolactin secretion

Reductions of prolactin secretion by bromocriptine treatment for 24 days reduced fat stores (abdominal and epididymal fat depots) in hamsters by 25-49% compared with control animals. However, body weights and food consumption were not affected. These results further substantiate an important role for prolactin in regulation of fat metabolism and indicate that bromocriptine might be used to decrease fat stores.     

Reduction of body fat stores by inhibition of prolactin secretion

Summary Reductions of prolactin secretion by bromocriptine treatment for 24 days reduced fat stores (abdominal and epididymal fat depots) in hamsters by 25–49% compared with control animals. However, body weights and food consumption were not affected. These results further substantiate an important role for prolactin in regulation of fat metabolism and indicate that bromocriptine might be used to decrease fat stores.     

Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development

Changes in mitochondrial function were studied in perfused liver from rats aged 24 – 365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage. Received 19 June 1998; received after revision 11 September 1998; accepted 11 September 1998     

Bitter peptides and bitter taste receptors

Bitter peptides are a structurally diverse group of oligopeptides often generated in fermented, aged, and hydrolyzed food products that make them unfavorable for consumption. Humans perceive bitterness by a repertoire of 25 human bitter receptors, termed T2Rs. Knowledge of the structural features of bitter receptors and of the factors that stimulate bitter receptors will aid in understanding the mechanism responsible for bitter taste perception. This article reviews the current knowledge regarding structural features of bitter peptides and bitter taste receptors. Received 24 November 2008; received after revision 11 December 2008; accepted 16 December 2008     

Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

聚焦超声辐照右足三里对痛阈的影响

目的观察聚焦超声辐照正常人右足三里对痛闽的影响。方法40例正常健康人，随机分成聚焦超声辐照组和安慰剂对照组，各20例。聚焦超声辐照右足三里30min，用Electronic Von Frey测定机械痛阈。在聚焦超声辐照前和开始辐照后10、20、30、40、50、60min记录机械痛阈。安慰剂对照组同时进行对比测量。结果超声辐照组，辐照前后左右两侧痛阈值分别有显著性差异（P〈0.01）；对照组，辐照前后左右两侧痛阈值均无统计学意义（左侧P=0．904，右侧P=0．274）。超声辐照组相邻时间水平有显著差异（P〈0．01），对照组相邻时间水平无显著差异；左右两侧不同部位间无显著性差异（P=0．176）；时间与部位无交互效应（P=0．411）。结论聚焦超声辐照单侧足三里后痛阈明显升高，从而具有一定的镇痛作用。     

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo

Summary High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.