In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.

Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems.     

鞘内远端吗啡预处理对大鼠心脏缺血-再灌注损伤的保护作用

目的 探讨鞘内远端吗啡预处理减轻在体大鼠心肌缺血-再灌注损伤的作用机制.方法 鞘内置管成功的雄性SD大鼠60只,随机(随机数字法)分为10组:缺血-再灌注组(I/R组)、鞘内远端吗啡预处理组(RMPC组)、CGRP8-37组、8-SPT组、HOE-140组、HEX组CGRP8-37+RMPC组、8-SPT+RMPC组、HOE-140+RMPC组和HEX+RMPC组.各组均采用缺血30 min再灌注120 min的方法制备心肌缺血/再灌注模型.RMPC组:在缺血前30 min内经5 min鞘内输注吗啡1 μg/kg(用生理盐水稀释到10 μL),停止5 min,共3个循环;I/R组给予等容量生理盐水.CGRP8-37组、8-SPT组、HOE-140组、HEX组分别在缺血前40 min静脉注射CGRP8-37,8-SPT,HOE-140和HEX,CGRP8-37+RMPC组、8-SPT+RMPC组、HOE-140+RMPC组和HEX+RMPC组在注射吗啡前10 min分别静脉注射上述阻断剂,上述阻断剂的剂量分别为3 nmol/kg,7.5 mg/kg,300μg/kg,20 mg/kg,均用生理盐水稀释到0.3 mL.记录吗啡预处理前(基础值)、缺血前即刻、缺血30 min、再灌注120 min时MAP,HR以及MAP与HR的乘积(RPP).基础值和再灌注120 min时分别采集静脉血样,测定血清乳酸脱氢酶(LDH)活性,实验结束处死大鼠,取心肌组织,计算梗死区体积及梗死区面积与缺血危险区体积的比值(IS/AAR).结果 与L/R组比较,RMPC组IS体积、IS/AAR和再灌注120 min时血清LDH活性降低(P＜0.05或P＜0.01);与RMPC组比较,CGRP8-37+RMPC组、8-SPT+RMPC组、HOE-140+RMPC组和HEX+RMPC组IS体积、IS/AAR和再灌注120 min时血清LDH活性升高(P＜0.05或P＜0.01).结论 鞘内远端吗啡预处理减轻在体大鼠心脏缺血后损伤,与CGRP、腺苷以及缓激肽的体液机制和神经机制共同参与介导有关.

Abstract：

Objective To investigate the mechanism of the protective effects induced by intrathecally remote morphine preconditioning (RMPC) against myocardial ischemia-reperfusion (I/R) injury in rats.Method Male SD rats weighing 280 ～ 320 g were used in this study. A needle was inserted through a surgically created hole into the spinal cord space. Sixty male SD rats, in which intrathecal needle was successfully placed without complication, were randomly (random number) divided into 10 groups of 6 animals each. In group Ⅰ myocardial I/R was produced (I/R). In group Ⅱ morphine was given intrathecally in 3 repeated doses of 1 μg/kg at 5 mtn intervals before ischemia (RMPC). Antagonists CGRP8-37 (CGRP receptor antagonist), 8-SPT (adenosine receptor antagonist), HOE-140 (bradykinin B2 receptor antagonist) and HEX (autonomic nerve antagonist) were given intrathecally in group Ⅲ , Ⅳ, Ⅴ and Ⅳrespectively at 10 min before RMPC. In group Ⅶ, Ⅷ, Ⅸ and X CGRP8-37, 8-SPT, HOE-140 and HEX were given intrathecally respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 120 min reperfusion. At the baseline and the end of 120 min reperfusion venous blood samples were taken for determination of LDH activity. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct size area (IS). IS/AAR was calculated. Results The size of infarct area was smaller and IS/AAR ratio lower and significantly less LDH was released at the time of 120 min reperfusion in RMPC group (group Ⅱ) than in group I/R (group Ⅰ). The protective effects of RMPC was abolished by intravenously pretreatment with CGRP8-37, 8-SPT,HOE-140 and HEX. Conclusions CGRP, adenosine, bradykinin and autonomic nerve are involved in the protective effects of intrathecally remote morphine preconditioning against myocardial I/R injury.     

姜黄素预处理及缺血后处理对大鼠肾脏缺血再灌注损伤的保护作用

背景：有研究发现姜黄素预处理、缺血后处理对大鼠肾脏缺血再灌注损伤具有保护作用。目的：建立大鼠肾脏缺血再灌注损伤模型,观察姜黄素预处理、缺血后处理、姜黄素预处理联合缺血后处理对大鼠肾脏缺血再灌注损伤的保护作用。方法：60只SD雄性大鼠随机均分为5组,假手术组、肾脏缺血再灌注模型组、姜黄素组、缺血后处理组以及联合处理组。肾脏再灌注24h后,取下腔静脉血测定肌酐和尿素氮。肾组织测定超氧化物岐化酶活性和丙二醛含量,并行苏木精-伊红染色观察各组肾组织病理学变化。结果与结论：与假手术组比较,其余各组肌酐、尿素氮均升高（P〈0.05）。与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组的肌酐、尿素氮值在再灌注24h后均下降（P〈0.05）。与姜黄素组和缺血后处理组比较,联合处理组的肌酐更低（P〈0.05）。与假手术组比较,缺血再灌注模型组超氧化物歧化酶活性明显降低,丙二醛含量明显升高,差异有显著性意义（P〈0.05）。与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组的超氧化物歧化酶活性升高,丙二醛含量降低,差异有显著性意义（P〈0.05）。与姜黄素组和缺血后处理组比较,联合处理组的超氧化物歧化酶活性升高,差异有显著性意义（P〈0.05）。与假手术组比较,缺血再灌注模型组肾小管损伤明显;与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组肾小管损伤减轻明显,与姜黄素组和缺血后处理组比较,联合处理组损伤更轻。说明示姜黄素预处理和缺血后处理联合应用具有协同作用,可以更好的保护大鼠缺血再灌注损伤肾脏。     

A non-toxic heat shock protein 70 inducer, geranyl-geranyl-acetone, restores the heat shock response in gastric mucosa of protein-malnourished rats

Acute gastric mucosal lesions caused by stress or noxious stimuli are important to consider in the management of critically or chronically ill patients. Protein malnutrition has been implicated as a risk factor for stress ulcer and subsequent complications in those patients. When male Wistar rats fed a 5% or 20% casein diet for 3 weeks were exposed to restraint and water-immersion stress, the low-protein diet significantly increased the ulcer index. The low-protein diet did not change the level of heat shock factor 1 (HSF1) in gastric mucosa but it did attenuate the HSF1 activation after exposure to the stress, resulting in the inhibition of HSP70 mRNA expression and HSP70 induction in gastric mucosa. HSP70 is crucial for the maintenance of cell integrity during pathophysiologic conditions; therefore the impaired HSP70 induction appeared to at least in part aggravate stress ulcer. We also tested whether a non-toxic HSP70 inducer, geranyl-geranyl-acetone (GGA), effectively improved the mucosal integrity by stimulating HSP70 induction under protein malnutrition. Intragastric administration of GGA (200 mg/kg twice a day) to the protein-malnourished rats for up to 1 week failed to stimulate the HSP70 induction. However, the administration of GGA (200 mg/kg twice a day) for 3 weeks restored HSP70 induction and induced higher resistance against stress ulcer as compared with results in vehicle-treated, normally nourished rats. Our results suggest that GGA may have a potential benefit for the prevention of stress ulcer in chronically or critically ill patients with protein malnutrition.     

缺血预处理模型大鼠心肌组织小分子热休克蛋白的表达

背景:小分子热休克蛋白,尤其是热休克蛋白27和α-B晶体蛋白高表达量对于心肌组织缺血再灌注的保护作用已比较明确.但是在老龄大鼠中小分子热休克蛋白是否仍具有这种保护作用迄今仍无报道.目的:观察热休克蛋白27和α-B晶体蛋白在青年及老年大鼠心肌缺血预处理时表达的变化.方法:24月龄老龄大鼠及两三月龄青年大鼠在体心脏经缺血5 min、再灌注5 min(反复3次)预处理后,于0,5,15,45,60 min取左心室缺血的前壁与非缺血的后壁心肌组织分别匀浆,分离上清及沉淀蛋白,用Western Blot检测热休克蛋白27和α-B晶体蛋白在预处理不同时间可溶性蛋白及不溶性蛋白含量的改变;采用RT-PCR方法观察缺血预处理对青年及老龄大鼠热休克蛋白27和α-B晶体蛋白mRNA在不同时间点表达的改变情况,采用免疫荧光观察缺血预处理后不同时间点热休克蛋白27和α-B晶体蛋白的移位情况.结果与结论:老龄大鼠在缺血预处理后热休克蛋白27和α-B 晶体蛋白表达量增加,表明老龄大鼠仍具有正常的基因转录及蛋白合成的能力;与青年大鼠比较,老龄大鼠缺血预处理后小分子热休克蛋白移位能力降低,从而减弱了与各相应蛋白结合的能力,限制其保护作用的发挥.提示老年大鼠心肌组织中小分子热休克蛋白丧失移位能力,可能是老年大鼠缺血预处理保护作用减弱的重要原因之一.     

缺血预处理模型大鼠心肌组织小分子热休克蛋白的表达冰

背景：小分子热休克蛋白,尤其是热休克蛋白27和a-B晶体蛋白高表达量对于心肌组织缺血再灌注的保护作用已比较明确。但是在老龄大鼠中小分子热休克蛋白是否仍具有这种保护作用迄今仍无报道。目的：观察热休克蛋白27和a-B晶体蛋白在青年及老年大鼠心肌缺血预处理时表达的变化。方法：24月龄老龄大鼠及两三月龄青年大鼠在体心脏经缺皿5min、再灌注5min（反复3次）预处理后,于0,5,15,45,60min取左心室缺血的前壁与非缺血的后壁心肌组织分别匀浆,分离上清及沉淀蛋白,用WesternBlot检测热休克蛋白27和a-B晶体蛋白在预处理不同时间可溶性蛋白及不溶性蛋白含量的改变;采用RT-PCR方法观察缺血预处理对青年及老龄大鼠热休克蛋白27和a-B晶体蛋白mRNA在不同时间点表达的改变情况,采用免疫荧光观察缺血预处理后不同时间点热休克蛋白27和CI-B晶体蛋白的移位情况。结果与结论：老龄大鼠在缺血预处理后热休克蛋白27和a-B晶体蛋白表达量增加,表明老龄大鼠仍具有正常的基因转录及蛋白合成的能力;与青年大鼠比较,老龄大鼠缺血预处理后小分子热休克蛋白移位能力降低,从而减弱了与各相应蛋白结合的能力,限制其保护作用的发挥。提示老年大鼠心肌组织中小分子热休克蛋白丧失移位能力,可能是老年大鼠缺血预处理保护作用减弱的重要原因之一。     

脑源性神经营养因子预处理对沙土鼠脑缺血-再灌注损伤的影响

目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)预处理对沙土鼠脑缺血-再灌注(ischemia-reperfusion,I/R)后神经细胞凋亡及Bcl-2、Bax蛋白表达的影响.方法 蒙古种沙土鼠48只,随机分为6组,每组各8只:正常对照组(C);缺血-再灌注组(I/R),全脑缺血20 min后再灌注24 h;BDNF预处理6,12,24,48 h组(PR6,PR12,PR24,PR48),PR6,PR12,PR24,PR48各组分别于脑缺血前6,12,24,48 h经侧脑室注射BDNF(0.5 μg/只)进行预处理,缺血20 min后分别再灌注24 h.实验地点在贵阳医学院动物实验中心.采用夹闭沙土鼠双侧颈总动脉20 min后去除动脉夹使血流再通的方法制作全脑I/R损伤模型,夹闭过程中出现瞳孔散大、对光反射消失及翻正反射消失等则说明产生全脑缺血.除C组外的所有动物分别于脑缺血20 min再灌注24 h结束时断头取脑,取视交叉后1～4 mm处的额叶皮层组织制备石蜡切片,TUNEL法检测脑皮层凋亡神经细胞,免疫组化法检测Bcl-2,Bax蛋白的表达.统计分析采用方差分析法.结果 C组未检测到凋亡细胞及Bcl-2,Bax蛋白阳性表达细胞;I/R组及BDNF预处理各组沙土鼠脑皮层均可检测到凋亡细胞,且BDNF预处理各组细胞凋亡指数均明显低于I/R组,P值均为0.000;与I/R组比较,BDNF预处理各组脑皮层Bcl-2蛋白阳性细胞指数均显著增高,而Bax蛋白的阳性细胞指数均显著降低,P值均为0.000;BDNF预处理各组中以6,12 h预处理组的细胞凋亡指数及Bax蛋白阳性细胞指数较低,P值分别为0.056和0.001,而Bcl-2蛋白阳性细胞指数较高,P值为0.005.结论 不同时间窗的BDNF预处理均能不同程度的减轻脑I/R后神经细胞凋亡,有明显脑保护作用,以脑I/R损伤前6,12 h时间窗内给予BDNF预处理的脑保护效果较明显;其机制可能是通过上调Bcl-2蛋白的表达及抑制Bax蛋白的表达而实现.     

优降糖对KATP通道介导缺血预适应心肌再灌注损伤的影响

目的 :探讨优降糖在完整大鼠心脏模型中 ,对 ATP敏感钾通道 (KATP)介导心肌缺血预适应作用的影响。方法 :将 4 4只大鼠随机分为 4组 :心肌缺血预适应组 (IPC组 )、优降糖组 (GL I组 )、优降糖 IPC组 (G P组 )和对照组 (C组 )。心肌缺血预适应由 3次 10分钟缺血和 10分钟再灌注组成。所有大鼠均接受 30分钟缺血和 6 0分钟再灌注。梗死范围由饱和曲利本蓝和红四氮唑蓝染色判定 ,并以坏死区占缺血区的百分比表示。 导联记录心脏室性心律失常。结果 :IPC能显著缩小缺血再灌注后的心肌梗死范围 ,且这种作用能被 KATP通道阻滞剂优降糖完全取消。 IPC可减少缺血再灌注所致的室性心律失常的发生 ,但这种保护作用不能被优降糖所阻断。结论 :优降糖对 KATP介导 IPC的心肌保护作用有影响。     

潘生丁预处理对大鼠肝缺血/再灌注损伤的保护作用

目的探讨潘生丁预处理对肝缺血／再灌注损伤的保护作用。方法 SD大鼠30只，随机分为假手术组、缺血／再灌注组及潘生丁组，每组10只。常温下制备大鼠肝缺血／再灌注损伤模型，潘生丁组于缺血前30min经门静脉给予潘生丁10mg／kg加生理盐水至0．5ml，假手术组和缺血／再灌注组注人等量生理盐水，用小号无损伤钳阻断肝门45min后恢复血流灌注，并于1h后取门静脉血测定血清丙氨酸转氨酶（ALT）、乳酸脱氢酶（LDH）、肿瘤坏死因子-α（TNF-Ⅱ）及内皮素-1（ET-1），同时取肝组织行病理组织学检查及腺苷酸含量测定。结果缺血／再灌注组血清ALT、LDH、TNF-α及ET-1均明显高于假手术组，潘生丁组则明显低于缺血／再灌注组（P均〈O．01）。缺血／再灌注组肝组织中腺苷酸含量明显低于假手术组，潘生丁组则明显高于缺血／再灌注组（P均〈O．01）。潘生丁组肝组织病理组织学改变明显轻于缺血／再灌注组，并接近假手术组。结论潘生丁预处理对肝缺血／再灌注损伤具有保护作用。     

异丙酚预处理诱导PC12细胞缺氧耐受作用研究

目的 观察异丙酚预处理对PC12细胞缺氧损伤的影响.方法 对数生长期的PC12细胞分为四组:对照组(C组),普通培养箱内常规培养;脂肪乳剂组(F组),在细胞培养基中加入10%脂肪乳剂,置普通培养箱内常规培养;缺氧组(H组),细胞置三气培养箱内培养,设置培养条件为2% O2、5% CO2;异丙酚+缺氧组(PH组),在细胞培养基中加入终浓度为2 mmol/L的异丙酚,再置入三气培养箱培养,条件设置同H组.四组细胞均在培养4 h后行细胞活力和细胞凋亡检测.结果 C组与H组之间细胞活力和细胞凋亡率的差异有统计学意义(P<0.05);与H组相比,PH组细胞活力明显增高(P<0.05),细胞凋亡率明显降低(P<0.05).结论 异丙酚预处理改善PC12细胞活力,通过抑制细胞凋亡诱导PC12细胞缺氧耐受.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.