雷公藤内脂醇对脓毒症大鼠免疫平衡的调节作用

目的：探讨雷公藤内脂醇对脓毒症大鼠血清促炎与抗炎介质的调节作用。方法：90只SD大鼠随机分为3组,每组30只;假手术组（A组），脓毒症模型组（B组）和雷公藤内脂醇治疗组（C组）。A组除不结扎也不刺穿盲肠外，余操作同B组。B组开腹后显露盲肠,根部结扎并刺穿肠壁2次,然后关腹，B组成功后不做任何处理。C组在盲肠结扎和穿孔后立即用雷公藤内脂醇(0.05mg/mL)腹腔注射0.2mg/kg,每隔8ｈ追加1次。各组大鼠在术后6，12，24ｈ分批处死,每批10只。取下腔静脉血检测血清中TNF-α，IL-1，IL-10和TGF-β的水平，并取肝、肾组织行HE及电镜检查。 结果：A组血清中炎症介质水平各时点无明显差异，肝肾功能与形态的变化不明显。B，C组炎症介质水平和抗炎介质水平均显著升高,肝肾功能与形态出现损伤性变化;C组较B组血中两者水平明显降低, 肝肾功能与形态损伤减轻。 结论：雷公藤内脂醇能降低脓毒症大鼠炎症介质水平，即对免疫平衡有调节作用，并减轻肝肾损伤。     

缺血预处理对大鼠减体积肝移植后Ref-1蛋白表达的影响

目的观察缺血预处理(ischemia preconditioning,IPC)对大鼠减体积肝移植术后氧化还原因子-1(redox factor-1,Ref-1)蛋白表达的影响,以探讨IPC对减体积肝移植损伤的保护作用及其机制。方法将100只Lewis成年雄性大鼠随机分成三组:IPC移植组(IPC组)、50%减体积肝移植组(PLT组)和假手术组(SO组),分别于移植后0．5 h、2 h、6 h和24 h取材,通过Western blot法和免疫组织化学技术结合图像分析定量检测移植后各时间点Ref-1表达变化,同时结合血清学和组织病理学分析Ref-1表达变化的意义。结果术后PLT组各时间点血清ALT值分别为(595．06±108．78)U/L;(723．18±117．24)U/L;(1186．65±142．31)U/L;(1498．91±126．79)U/L;IPC组术后各时间点血清ALT值分别为(459．06±84．73)U/L;(587．71±95．23)U/L;(799．61±125．97)U/L; (659．27±135．68)U/L。与PLT组相比,IPC组术后6 h和24 h血清ALT值明显降低(t=4．553, P＜0．05;t=10．110,P＜0．01)。病理学分析显示,PLT组术后24 h门静脉周围大量炎细胞浸润,肝窦扩张明显,肝组织损伤较重;而IPC组则损伤较轻。与PLT组相比,IPC组于减体积肝移植术后24 h肝实质细胞中Ref-1蛋白表达明显增高。结论缺血预处理可以减轻减体积肝移植后早期肝脏损伤,促进肝组织Ref-1蛋白表达,提示缺血预处理保护减体积肝移植物早期损伤的机制可能与促进Ref-1蛋白的表达有关。     

乙酰半胱氨酸对脑死亡大鼠肝脏的保护作用

目的探讨乙酰半胱氨酸(NAC)对脑死亡大鼠肝脏损伤的保护作用。方法将30只大鼠随机分为空白对照组(C)、脑死亡组(B)、NAC保护组(N)。各组动物均于脑死亡4h后采集血清检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、透明质酸(HA)及肿瘤坏死因子α(TNFα),并切取肝组织行电镜观察。结果脑死亡4h后,B组、C组和N组血清ALT水平(U/L)分别是142.88±4.12、43.38±2.33和101.38±5.37,AST水平(U/L)是283.00±12.74、120.38±4.07和216.54±7.16,HA(μg/L)是168.98±2.59、61.14±1.10和139.31±2.61,TNFα(μg/L)是1.26±0.041、0.62±0.03和0.96±0.07;B组较C组、N组显著升高(P<0.05),N组较C组显著升高但明显低于B组(P<0.05)。电镜观察示B组大鼠肝脏Kupffer细胞明显活化、肝窦内皮细胞与基质部分脱落、肝窦内皮窗口扩大,N组Kupffer细胞活化明显减轻、内皮细胞基本完整。结论脑死亡可致大鼠肝脏损伤,NAC对脑死亡大鼠肝脏损伤具有保护作用。     

重组人红细胞生成素对脓毒症大鼠肾脏的保护作用

目的 探讨重组人红细胞生成素(rHuEPO)对盲肠结扎穿孔术(CLP)所致大鼠脓毒症急性肾损伤(AKI)的保护作用.方法 260只雄性SD大鼠随机分为正常对照组、假CLP组(假手术组)、CLP组(脓毒症组)和rHuEPO大、中、小剂量组.采用CLP复制脓毒症模型,rHuEPO大、中、小剂量组造模后即刻分别静脉推注rHuEPO 5000 U/kg、1000 U/kg、500 U/kg.假CLP组、CLP组、rHuEPO大、中、小剂量组按注药后2h、6h、12 h、24 h、36 h时点分成5个亚组,分别在各时点按随机原则处死大鼠.采用ELISA法测定血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、肾损伤分子1(KIM-1)、诱导型一氧化氮合酶(iNOS)的水平;免疫组化法检测大鼠肾组织NF-κB蛋白表达;光镜和透射电镜观察肾组织形态学变化.结果 与CLP组相比,rHuEPO大剂量组大鼠各时间点血清Scr、BUN、TNF-α、IL-6、KIM-1、iNOS的含量及肾组织NF-κB蛋白表达水平均显著降低,差异有统计学意义(P＜0.05);肾脏病理改变好转.rHuEPO中、小剂量组肾脏病理改变未见好转.结论 rHuEPO能够降低脓毒症大鼠血清TNF-α、IL-6、iNOS、KIM-1水平进而调节炎性反应及肾功能,对脓毒症所致AKI具有一定的保护作用.     

胰蛋白酶抑制剂对脓毒症大鼠肠黏膜屏障的保护作用

目的探讨胰蛋白酶抑制剂乌司他丁对脓毒症大鼠肠黏膜屏障的保护作用。方法将 2 2只SD大鼠随机分为 3组 :假手术组、脓毒症组及干预组。利用盲肠结扎打孔法 (cecalligationandpunture ,CLP)制作大鼠脓毒症模型 ,干预组分别于CLP后 5h、15h腹腔给予 7 5× 10 4U/kg体重的乌司他丁 (ulinastatin ,UTI)。应用荧光光谱分析仪检测至肠腔进入门静脉的荧光标记葡聚糖(FITC D)的浓度 ,了解UTI对肠黏膜通透性的影响。同时 ,用透射电镜观察肠黏膜机械屏障的变化。结果CLP 2 1h后干预组动物脓毒症表现轻 ,假手术组门静脉FITC D浓度 (1 2 2± 0 2 1) μg/ml,而脓毒症组 (2 5 1± 0 5 6 ) μg/ml高于假手术组 (F =5 0 31,P <0 0 1) ,干预组 (1 5 7± 0 5 0 ) μg/ml则低于脓毒症组 (F =1 2 4 9,P <0 0 1)。脓毒症组肠黏膜机械屏障明显受损 ,而干预组肠屏障受损较轻。结论给予乌司他丁对脓毒症大鼠肠黏膜屏障有明显的保护作用。     

性别差异对脓毒症大鼠肝脏Toll样受体4和髓样分化蛋白-2基因表达的影响

目的探讨性别差异对脓毒症大鼠肝脏组织Toll样受体4(TLR4)和髓样分化蛋白- 2(MD-2)基因表达的影响。方法以脂多糖(LPS)按5 mg/kg体重由大鼠腹腔注射制作脓毒症动物模型,注射后2 h留取肝脏组织检测TLR4、MD-2和肿瘤坏死因子-α(TNF-α)基因表达,同时测定各组大鼠血浆中丙氨酸氨基转移酶(ALT)及雌二醇含量。结果正常雌雄性大鼠肝脏组织均可表达少量TLR4、MD-2、TNF-α基因,其中雌性组分别为0．175±0．034、0．211±0．044、0．201±0．068; 雄性组分别为0．205±0．061、0．243±0．049、0．243±0．063,两组数据差异无统计学意义(P> 0．05),但LPS刺激后雌性大鼠肝脏组织上述指标分别为0．615±0．089、0．708±0．181、0．730± 0．118,血浆中ALT含量为(81．07±10．72)U／L;雄性组分别为0．723±0．091、1．123±0．272、 0．881±0．156,ALT含量为(106．39±14．21)U／L,雌性组各项指标均明显低于雄性大鼠(P< 0．05)。相关分析表明雌性及雄性脓毒症大鼠肝脏组织TLR4及TNF-α基因表达与相应性别大鼠血浆中雌二醇含量呈显著负相关(P<0．05)。结论 LPS刺激后大鼠肝脏组织TLR4、MD-2及 TNF-α基因表达存在性别差异,内源性雌激素的作用可能导致雌性脓毒症大鼠肝脏组织损伤较雄性轻。     

丙氨酰-谷氨酰胺二肽保护大鼠肝脏缺血再灌注损伤的实验研究

目的探讨丙氨酰-谷氨酰胺二肽(Ala-Gln)对肝脏缺血再灌注损伤(HIRI)的保护作用.方法采用大鼠HIRI模型(Pringle's法阻断入肝血流30 min),分谷氨酰胺组(G组)及对照组(C组),检测再灌注后血清肝生化酶、肝组织还原型谷胱甘肽(GSH)及超氧化物歧化酶(SOD)水平,对肝组织进行光镜与电镜检查,并计算术后24 h生存率.结果再灌注1h,G组血清ALT(499.25±120.84)U/L、LDH(6 956.00±2 443.93)U/L的水平均显著低于C组(ALT823.56±328.71,P<0.05;LDH11 715.31±2 993.50,P<0.01);再灌注24 h,两组血清ALT、LDH的水平均有显著恢复,但G组(ALT176.69±151.84;LDH415.38±213.68)水平仍显著低于C组(ALT548.25±257.25;LDH1 958.50±687.32;P<0.01).再灌注1 h及24 h,G组GSH的水平分别为(1 216.09±152.78)μg·g-1·p、(899.73±57.75)μg·g-1·p,均明显高于C组(分别为856.68±117.64,P<0.01;800.50±94.79,P<0.05);两组SOD的活性无统计学差异.G组肝脏组织学与细胞学损害均明显轻于C组.G组术后24h生存率为78.57%(11/14),明显高于C组的45.45%(10/22)(P<0.05).结论 Ala-Gln(Gln)对HIRI具有保护作用,而这种保护作用部分是通过维持肝脏组织中GSH的含量来介导的.     

肝缺血再灌注损伤中乌司他丁对核因子-κB活化的影响及对损伤的保护作用

目的探讨乌司他丁及核因子(NK)-κB在肝缺血再灌注(I/R)损伤中的作用。方法制作大鼠部分肝I/R模型,分为:A假手术组,B肝缺血90min组,C肝缺血90min、再灌注120min组,D肝缺血90min、再灌注120min加乌司他丁组。光镜观察肝脏组织学改变,测定血清酶学水平和肝组织中髓过氧化物酶(MPO)含量,sABC免疫组织化学方法测定肝组织中NF-κB的活化程度。结果A组肝细胞索排列有序,肝细胞形态正常;B组肝小叶结构紊乱,肝血窦和中央静脉有轻度淤血,内皮细胞和肝细胞水肿变性;C组肝细胞坏死较明显,D组上述改变明显减轻;B组的血清ALT、AST和MPO分别为454.1±26.2、819.1±18.2I U/L和0.908±0.189U/g,肝组织NF-κB活化程度为1.89±0.12(与A组比较,P<0.05);C组分别为1156.9±216.3、2150.5±209.8I U/L和2.126±0.160U/g,肝组织NF-κB活化程度为2.86±0.20(与A组比较,P<0.01);D组分别为553.6±19.4、897.6±23.9I U/L和1.128±0.162U/g,肝组织NF-κB活化程度为2.04±0.16(与C组比较,P<0.01)。结论乌司他丁能减轻NF-κB活化,减轻肝I/R时中性粒细胞通过释放蛋白酶造成的肝损伤。     

海水浸泡对烫伤大鼠创面炎性反应与愈合的影响

目的观察海水浸泡对烫伤大鼠创面炎性反应及愈合的影响。方法将144只雄性Wistar大鼠随机分为烫伤对照组和海水浸泡组,每组72只,均造成背部10%TBSA浅Ⅱ度烫伤。海水浸泡组大鼠伤后固定四肢,立即用盛海水的方盆浸泡双前肢以下部分,持续4h；烫伤对照组大鼠则用空方盆模拟浸泡过程。于伤后0(即刻,下同)、6、12、24h采用电解质分析仪测定血清中K~+、Na~+、Cl~-的浓度。于伤前及伤后0、6、12h采用酶联免疫吸附测定法检测血清中肿瘤坏死因子(TNF)α及白细胞介索(IL)6的含量。对两组大鼠创面行大体和组织病理学观察,并记录创面愈合时间。结果海水浸泡组大鼠血清中K~+、Na~+、Cl~-的浓度大多高于烫伤对照组。伤后6h海水浸泡组大鼠血清TNF-α、IL-6含量分别为(140±22)、(160±41)ng/L,均明显高于伤前值(29±15)、(62±17)ng/L及烫伤对照组(120±12)、(124±22)ng/L(P＜0．05)。与烫伤对照组比较,海水浸泡组大鼠创面水肿及局部组织炎性反应加重,创面再上皮化和表皮各层的分化延迟；海水浸泡组创面愈合时间为(16．3±1．6)d,明显迟于烫伤对照组(14．1±1．8)d(P＜0．05)。结论大鼠烫伤后经海水浸泡,可加重创面炎性反应,使创面愈合延迟。     

回盲肠间置代幽门术对糖代谢作用的影响

目的研究将回盲肠间置幽门替代术应用于胃肠道重建中的可行性。方法将21例成年健康小型猪分为3组:假手术对照组、BⅠ式组和远端胃大部切除带蒂回盲肠间置幽门替代手术组(回盲肠间置组),在术后60和120d时口服葡萄糖后在0、30、60、90和120min用快速血糖试纸法测血糖浓度,比较胃对流质的排空情况,观察术后动物恢复情况。结果术后2个月,峰值血糖浓度BⅠ式组为(7.8±1.0)mmol/L,回盲肠间置组为(7.1±0.8)mmol/L,假手术对照组为(4.1±0.4)mmol/L;前两组与假手术对照组比较,差异均有非常显著的统计学意义(P<0.01)。4个月后,回盲肠间置组峰值血糖浓度为(5.2±0.8)mmol/L,对照组(4.2±0.5)mmol/L,BⅠ式组(6.9±1.0)mmol/L。回盲肠间置组与假手术对照组比较,差异无统计学意义(P>0.05);但这两组与BⅠ式组比较,差异均有非常显著的统计学意义(P<0.01)。结论回盲肠间置幽门替代术重建消化道具有可行性。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.     

Intraoperative autotransfusion is associated with modest reduction of allogeneic transfusion in prosthetic hip surgery

Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r²=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.     

缺氧对肾小管上皮细胞分泌外泌体的影响

目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    （1）常氧（21% O₂）及缺氧（1% O₂）分别处理大鼠肾小管上皮细胞（NRK-52E）48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。（2）在共培养实验中,以不同浓度（1、10、50、100、300 mg/L）的常氧外泌体、缺氧外泌体分别干预脂多糖（LPS）诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验（ELISA）法分别检测巨噬细胞白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、诱导型氮氧化物合酶（iNOS）水平;使用Western印迹法检测巨噬细胞磷酸化（p）STAT/STAT及细胞因子信号传导抑制蛋白1（SOCS1）的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA（microRNA,miR）的表达差异。 结果    （1）离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。（2）缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌（均P＜0.01）,同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达（均P＜0.01）;对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高（P＜0.05）。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。     

In Vitro Function and Durability Assessment of a Novel Polyurethane Heart Valve Prosthesis

Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.     

Negative pressure ventilation vs. spontaneous assisted ventilation during rigid bronchoscopy: A controlled randomised trial

Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O₂ flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg^?1· h^?1 vs. 6.6 ± 4.8 μg · kg^?1· h^?1), a lower O₂ supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO₂ was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.