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1.
目的探讨异种肝细胞移植对大鼠急性肝功能衰竭防治效果及其免疫排斥反应。方法将异种豚鼠肝细胞,90%肝除术前1d植入大鼠脾脏内。观察受试大鼠存活时间,及切肝术后24h血生化改变。另外观察植入肝细胞被排斥情况及受体CH50、异种抗体IgG、IgM水平变化。结果(1)中位存活时间,对照组为21h,同种组为56h,异种组为40h。同种组存活时间较对照组延长(P<0·01),异种组亦延长(P<0·05)。(2)异种组血糖和凝血酶原时间改善较明显(P<0·05),同种组谷丙转氨酶、总胆红素、血糖、凝血酶原时间都有明显改善(P<0·05或P<0·01)。(3)受体CH50和异种抗体IgM水平下降与植入异种肝细胞排斥过程同步。结论异种肝细胞移植对大鼠急性肝功能衰竭有防治作用,补体和异种抗体IgM与排斥反应关系密切。  相似文献   

2.
目的研究肝细胞腹腔移植治疗急性肝功能衰竭的免疫排斥反应。方法用胶原酶灌注法分离幼猪及BALB/c和C57BL/6小鼠肝细胞;用腹腔注射CCl4的方法建立C57BL/6急性肝功能衰竭模型;将实验动物分为同基因移植组、同种异基因移植组和异种移植组。各组动物肝细胞移植入急性肝功能衰竭小鼠腹腔内,观察受体小鼠存活情况,比较各组动物T细胞亚群、免疫球蛋白水平和细胞因子的变化。结果①受体小鼠存活情况:同基因移植组为8/10,同种异基因移植组为6/10,异种移植组为3/10,同基因移植组和同种异基因移植组受体的生存情况明显好于异种移植组(P<0.05)。②T细胞亚群变化:移植后7 d内,同基因移植组外周血中CD4+和CD8+T细胞均无明显变化,同种异基因移植组CD4+T细胞于移植后3 d时达高峰(P<0.05),而CD8+T细胞7 d内无明显变化,异种移植组CD4+和CD8+T细胞移植后7 d内均明显升高,且于移植后3 d时达高峰(P<0.05)。③免疫球蛋白水平:同基因移植组血清免疫球蛋白IgM和IgG水平在移植后0.5、1和3 d时未见明显变化,同种异基因移植组和异种移植组的IgM在移植后1 d时达高峰(P<0.05),而IgG在移植后3 d时达高峰(P<0.05)。④血清细胞因子水平:移植后7 d,同种异基因移植组和异种移植组的IFN-γ、TNF-α及IL-2血清浓度明显高于同基因移植组(P<0.05);异种移植组的IL-6血清浓度明显高于同基因移植组和同种异基因移植组(P<0.05)。结论无论同种还是异种肝细胞移植,初期均发生了强烈的CD4+及CD8+T细胞参与的细胞免疫和较强体液免疫反应。  相似文献   

3.
实验研究已经证明一种用AN-69凝胶合成的半透膜管可以保护肝细胞的同种异体移植,延长肝细胞的生存时间,这种技术可用于纠正某些肝细胞酶先天性缺乏,提高大鼠急性肝功能衰竭的生存率。但肝细胞同种移植受到许多因素的限制。本研究的目的是:1.观察这种半透膜管对肝细胞异种移植的免疫保护作用。2.研究宿主对装管移植异种肝细胞的免疫反应。 材料与方法: 分别取肝脏手术切除小块人肝组织和同种大鼠肝组织,用胶原酶A灌注消化法分离肝细胞。分离好的肝细胞混悬液装入AN-69凝胶制备的半透膜微管内,每只大鼠移植2×10~7个肝细胞。这种半透膜管具有良好的生物相容性和半透膜特性,微孔直径约160kDa。选Lewis大鼠作为肝细胞移植的受体,装有肝细胞的微管植入大鼠腹腔。实验分为5组,每组10只大鼠;第一组植入装管人肝细胞,第二组植入游离的人肝细胞,第三组植入装管大鼠肝细胞,第四组只植入空管,第五组植入空管和肝细胞培养液。移植前、移植后第2、7、和21天分别抽血分离血清,观察指标包括1、用聚丙烯  相似文献   

4.
目的 探讨微囊化同系、同种异体、异种肝细胞腹腔移植对急性肝衰(acute liver failure,ALF)的治疗作用。方法 切除大鼠90%的肝脏,建立急性肝衰模型;分离纯化包裹同系Wistar鼠,同种异体SD鼠及异种豚鼠的肝细胞。移植到受体模型鼠腹腔内,观察微囊存活情况及肝衰鼠的生存率和生化改变。结果 在48h内对照组存活率仅15.4%,而同系肝细胞组为78.6%,SD微囊组73.3%,GP微囊组62.5%,7d后对照组大鼠全部死亡,而其余3组存活率分别为57.1%,、53.3%、50.0%。微囊化肝细胞组ALT和TBIL的水平明显降低,与对照组相比差异有非常显著性(P〈0.01)。结论 微囊包裹同种异体和异种肝细胞腹腔移植而不使用免疫抑制剂,能够阻止免疫排斥反应,给予肝功能代谢支持,阻止急性肝衰模型鼠的死  相似文献   

5.
目的 探讨中药川芎嗪对大鼠肝脏缺血.再灌注损伤是否具有保护作用.方法 132只SD大鼠随机分为3组:A组(空白对照组)、B组(缺血-再灌注组)、C组(治疗组),于术前及再灌注后30 min、6 h、24 h抽血检测ALT、AST及LDH,同时观察组织病理学变化,对比每组大鼠1周累积生存情况:免疫组化检测肝细胞凋亡指数.结果 C组累积生存率高于B组(P<0.05).B组及C组ALT、AST及LDH均明显高于A 组(P<0.05)且C组低于B组(P<0.05),光镜下,缺血-再灌注后肝细胞坏死情况B组重于C组,B组肝细胞凋亡指数高于C组(P<0.05).结论 川芎嗪对大鼠肝脏缺血-再灌注损伤具有明显的保护作用.  相似文献   

6.
辅助性肝移植治疗大鼠急性肝功能衰竭的实验研究   总被引:3,自引:0,他引:3  
Lu Y  Pan C  Liu X  Meng L  Qin Z  Zhang M 《中华外科杂志》1998,36(9):519-521
目的探讨辅助性肝移植对急性肝功能衰竭(简称肝衰)的治疗作用。方法在30只肝功能衰竭大鼠模型上,于原残肝下移植同系异体62%部分肝脏,手术成功28例。观察了肝衰组和移植组大鼠存活、血液生化、99mTcHIDA肝显像、残肝和移植肝组织细胞形态改变。结果肝衰组(15只)和移植组(28只)大鼠48小时存活率分别为0%和71.4%。移植术后14天残肝细胞明显增生,肝功能基本恢复正常,辅助肝开始萎缩,术后30天辅助肝完全纤维化。结论辅助性部分肝脏异位移植可为衰竭之残肝提供暂时性功能支持。原残肝细胞再生,功能恢复过程中辅助肝逐渐萎缩、废用  相似文献   

7.
研究分离Sprague-Dawley大鼠肝细胞的方法及短期培养后对细胞活性的影响。并研究新鲜分离的同种异体肝细胞移植对实验性急性肝功能衰竭的治疗作用。方法 采用胶原酶原位和循环灌注法分离肝细胞;游离肝细胞在合成RPMI164培养基内培养6天测定细胞内生化指标;用D-氨基半乳糖将60只雄性SD大鼠制成急性肝功能衰竭模型并同均分为移植组和对照组,将新鲜离体肝细胞悬液注入移植组大鼠腹腔内,对照组则注入等  相似文献   

8.
异种肝细胞移植排斥机理的探讨   总被引:7,自引:0,他引:7  
目的:探讨异种肝细胞排斥反应的机理,为治疗异种肝细胞移植排斥反应提供理论依据。方法,用D-氨基半乳糖腹腔内注射制成肝功能衰竭大鼠模型,并在其脾内植入豚鼠肝细胞,通过免疫组化方法,用抗大鼠IgM抗体和抗大鼠IgG抗体,抗大鼠CD4和抗大鼠CD8抗体与因排斥反应在大鼠脾 内可能产生的IgM,IgG抗体和CD4,CD8淋巴细胞结合,在移植后不同时间取受鼠脾脏标本,检测其内是否有IgM,IgG抗体和CD4,CD8淋巴细胞存在。结果:移植后12hIgM抗体存在,移植后24h大鼠脾内出现IgG抗体,同时有CD4^=和CD8^+淋巴细胞,且在移植后1周大鼠脾内均可见上述4种物质。结论:体液和细胞免疫均参与异种肝细胞移植的排斥反应。  相似文献   

9.
本实验通过同种异体大鼠肝细胞肾脏内移植,尝试在受体体内建立第二肝脏。对移植肝细胞进行长期组织形态与功能观察,并利用该方法进行急性肝功能衰竭肝功能辅助支持治疗研究。结果表明肝细胞肾脏内移植后可长期存活、增殖而且具有肝组织结构重建及保持肝脏功能的能力。4×107个肝细胞肾脏内移植后可显著提高受体大鼠对肝功能衰竭的承受力,移植组术后3天行90%肝切除诱发急性外科型肝功能衰竭后其存活率显著高于对照组。以上结果显示肾脏可以成为肝细胞移植又一适宜部位,肝细胞肾脏内移植有可能成为临床上肝脏代谢及功能障碍疾病的一种治疗手段。  相似文献   

10.
目的 探讨锌指蛋白A20对同种异体大鼠30%小体积移植肝再生与排斥及受体存活时间的影响.方法 采用急性排斥组合DA (RT1a)大鼠→Lewis (RT1l)大鼠建立同种异体大鼠30%小体积肝移植模型. 75只大鼠均分为A20腺病毒组(A20组)、对照空腺病毒组(rAdEasy组)及对照生理盐水组(PS组)3组. 供肝切取后采用离体门静脉灌注法转基因干预,肝脏灌洗后移植. 观察受体存活时间及排斥反应,检测移植肝A20表达、肝细胞再生与凋亡、肝血窦内皮细胞(LSECs)中NF-κB活性与ICAM-1 mRNA表达、移植肝浸润单核细胞(LIMCs)总数及自然杀伤(NK)细胞和自然杀伤T(NKT)细胞数以及血清IFN-γ水平. 结果 A20组受体大鼠存活时间长于PS组大鼠和rAdEasy组大鼠(P=0.001 8),而PS组大鼠存活时间又长于rAdEasy组大鼠(P=0.001 8). A20促进小体积移植肝再生,肝移植后4 d A20组大鼠肝细胞BrdU标记指数高于PS组大鼠和rAdEasy组大鼠(P<0.01); A20组大鼠肝细胞凋亡指数低于PS组大鼠和rAdEasy组大鼠(P<0.01). 肝移植术后4 d,组织学检测结果显示A20组大鼠移植肝有少量细胞浸润,呈轻度排斥; 而PS 组和rAdEasy组大鼠移植肝有大量细胞浸润,呈重度排斥. A20能抑制移植后早期(1 d) LSECs 中NF-κB活性和 ICAM-1 mRNA 表达. 流式细胞术检测结果显示A20能下调移植肝LIMCs数,包括下调NK和NKT 亚群细胞数,并下调血清IFN-γ水平(P<0.05). 结论 A20能有效促进同种异体大鼠30%小体积移植肝再生,抑制排斥并延长受体存活时间,其功效可能与抑制LSECs中NF-κB活性、抑制LIMCs浸润及减少NK 细胞和NKT 细胞浸润入肝以及抑制肝细胞凋亡有关.  相似文献   

11.
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 (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.  相似文献   

12.
Don Dame 《Artificial organs》1996,20(5):613-617
Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.  相似文献   

13.
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.  相似文献   

14.
Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H2O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg−1 followed by 0.15 mg · kg−1 · h−1, n=8) or verapamil (0.1 mg · kg−1 followed by 0.3 mg · kg−1 · h−1, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.  相似文献   

15.
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.  相似文献   

16.
Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.  相似文献   

17.
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.  相似文献   

18.
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.  相似文献   

19.
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.  相似文献   

20.
Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.  相似文献   

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