褪黑激素对严重烧伤大鼠心肌损害的保护作用

目的 探讨褪黑激素(MLT)对严重烧伤大鼠早期心肌损害的保护作用及机制.方法 将30只SD大鼠按随机数字表法分为假伤组、烧伤组和MLT组,每组10只.采用大鼠背部皮肤浸入沸水中15s造成30％总体表面积Ⅲ度烫伤复制烧伤动物模型;假伤组大鼠背部皮肤浸入37℃水中.伤后立即腹腔注射溶剂(1％乙醇生理盐水)或MLT 10 mg/kg.伤后6h鼠尾取血后处死大鼠,取心肌组织,检测丙二醛(MDA)和还原型谷胱甘肽(GSH)含量、谷胱甘肽过氧化物酶(GSH-Px)和髓过氧化物酶(MPO)活性,以及血清肌酸激酶(CK)和乳酸脱氢酶(LDH)水平.结果 与假伤组比较,烧伤后心肌组织MDA含量升高了66.7％(nmol/mg:1.55±0.17比0.93±0.05),GSH含量下降了27.8％(nmol/mg:13.58±0.33比18.82±0.55,均P＜0.01),GSH-Px活性被轻度抑制(nmol· min-1· mg-1:74.04±3.42比93.79±3.76,P＜0.05),MPO活性则增加至2.8倍(U/g∶9.43±1.15比3.41±0.27,P＜0.01),提示心肌产生明显的氧化应激损伤.除GSH-Px外,MLT治疗可改善上述各种异常,与烧伤组比较差异均有统计学意义[MDA (nmol/mg):0.89±0.08比1.55±0.17,GSH (nmol/mg):17.23±0.54比13.58±0.33,MPO(U/g):6.91±0.51比9.43±1.15,P＜0.05或P＜0.01].此外,烧伤后血清CK及LDH水平分别较假伤组增加至37.8倍和7.4倍(均P＜0.01);MLT治疗后二者分别降低了32.9％及21.2％(P＜0.05和P＜0.01).结论 MLT对严重烧伤早期的心肌损害具有保护作用,其机制可能和MLT抑制烧伤诱导的氧化应激损伤有关.     

促红细胞生成素对大鼠体外循环后肾脏保护作用的研究

目的研究促红细胞生成素(EPO)对于大鼠体外循环(CPB)术后肾脏损伤的保护作用并探讨其相关机制。方法将30只雄性SD大鼠随机均分为Sham组、CPB组及EPO组,每组10只。Sham组建立CPB模型管道,不进行CPB;其他2组建立CPB,以最大流量≥100 mL/(kg.min)转流维持1 h,其中EPO组于转流前在预充液中加入EPO 3 000 U/kg。分别于肝素化后转流前(T0)、转流结束后(T1)和转流结束后0.5(T2)、1(T3)、2(T4)、24 h(T5)检测血清肌酐(SCr)、尿素氮(BUN)水平;T5时取肾脏组织,检测组织肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)等炎症因子水平;同时测定肾脏组织丙二醛(MDA)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)等氧化应激指标水平,并行HE染色观察组织形态学改变。结果 T0时3组SCr、BUN水平无显著差异;与CPB组相比,EPO组T1至T 5各时间点SCr、BUN水平明显下降(P<0.05),肾组织中TNF-a、IL-1β、IL-6等炎症因子水平均明显低于CPB组(P<0.05);CPB组MDA高于Sham组,CAT、SOD活性则较Sham组低;EPO组CAT、SOD活性高于Sham组;组织病理学检查显示,EPO组的肾小管上皮细胞肿胀、胞浆内空泡形成、间质出血等病理变化较CPB组明显减轻(P<0.05)。结论 EPO可能通过抑制炎症因子的表达,降低氧化应激损伤,达到减轻CPB后肾脏损伤的目的。     

川芎嗪预处理对体外循环后心肌损伤的保护作用

目的探讨川芎嗪预处理在体外循环(CPB)心脏手术中的心肌保护作用及机制。方法28例非发绀型先天性心脏病患者,随机分为对照组和川芎嗪预处理组,每组14例。川芎嗪预处理组患者麻醉诱导后经颈内静脉滴入川芎嗪3mg/kg,30min滴完,转流后追加1mg/kg于氧合器中,对照组于上述时间给予等量生理盐水。两组分别于转流前、主动脉开放后30min和术后24h测定外周血天冬酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌酸磷酸激酶(CK)和肌酸磷酸激酶同工酶(CK-MB)的变化。同时,分别于转流前和主动脉开放后30min取右心耳心肌组织,观察心肌超微结构变化。结果两组主动脉阻断时间比较差异无统计学意义。CPB期间两组患者心肌损伤指标AST、LDH、CK、CK-MB明显升高(P<0.05),川芎嗪组心肌酶含量明显低于对照组(P<0.05)。川芎嗪组心肌超微结构受损较对照组为轻。川芎嗪组CPB后线粒体计分明显低于对照组(P<0.05)。结论川芎嗪预处理使患者心肌超微结构损害减轻,心肌线粒体结构和功能的完整性得到保护,心肌酶漏出减少,故川芎嗪预处理在CPB手术中有较好的心肌保护作用和应用前景。     

褪黑素保护大鼠肝纤维化的机制探讨

目的研究褪黑素保护大鼠肝纤维化的机制。方法用四氯化碳(CCl4)制造大鼠肝纤维化模型,同时予10 mg.kg-1.d-1褪黑素腹腔注射;在造模的第12周末处死大鼠,观察大鼠肝脏活化核转录因子κB(NF-κB)亚单位P65的表达。用α-SMA单抗标记活化的肝脏星状细胞(HSCs),计算其数量,同时测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白(ALB)水平及ALB与球蛋白(GLO)比值,并进行肝脏病理学评分。结果褪黑素抑制了NF-κB亚单位P65的活化,活化HSCs数量减少,ALT、AST降低,而ALB和ALB/GLO明显提高,肝脏炎症和纤维化显著减轻(P<0.05~0.01)。结论褪黑素通过抑制NF-κB的激活,减轻肝脏炎症,抑制了HSCs活化,使肝纤维化减轻。     

褪黑激素对严重烧伤早期肾功能损害的保护作用

目的观察褪黑激素（MLT）对严重烧伤大鼠肾组织氧化应激损伤和肾功能不全的保护作用及机制。方法将70只SD大鼠随机分为假手术组（10只）、烫伤组（用背部浸入沸水中30S造成30％总体表面积Ⅲ度烫伤模型，30只）和MLT治疗组（伤后立即腹腔注射MLT 10mg／kg，每12h补充注射1次，30只）。检测各组伤后6、24和72h肾组织丙二醛（MDA）和还原型谷胱甘肽（GSH）含量、血浆肌酐（BCr）及尿素氮（BUN）水平，以及伤后6h肾组织谷胱甘肽过氧化物酶（GSH-Px）和髓过氧化物酶（MPO）活性。结果烫伤后各时间点肾组织MDA水平明显升高，而GSH含量则显著下降，二者变化均以伤后6h最明显（P均〈0．01）。BCr及BUN水平在烧伤后6h达高峰（P均〈0．01），然后呈进行性下降。单次MLT治疗使伤后6h肾组织MDA水平降低27．8％（P〈0．01），使GSH含量提高44．4％（P〈0．05），并抑制BCr及BUN水平（P〈0．05和P〈0．01）。连续注射MLT对以上各指标均无明显影响。此外，MLT使烧伤后6h肾组织MPO水平降低30．2％（P〈0．05），但对GSH-Px活性无明显影响。结论30％Ⅲ度烫伤可导致大鼠肾脏发生明显的氧化应激损伤（伤后72h内）及急性肾功能不全（伤后24h内），单次MLT治疗对二者均具有一定的保护作用，可能与MLT具有强大的自由基清除能力及抑制中性粒细胞聚集有关。     

电针刺内关穴对体外循环大鼠心肌的保护作用

目的研究电针刺内关穴对大鼠体外循环（CPB）后白细胞黏附分子的调节和对心肌细胞凋亡的作用，从而探讨电针刺对体外循环后心肌保护作用的机制。方法30只大鼠随机分为3组，对照组、体外循环组（CPB组）和针刺内关组（EA组）。体外循环组采用MackensenGB的方法建立大鼠的体外循环模型；电针刺组采用电针刺双侧内关穴并维持到术后1h。术中采血血气分析，流式细胞仪全血法测定白细胞表面CDllb表达，术后取心肌PT—PCR测定Bcl-2和BaxmRNA表达，Western印迹分析Bcl-2和Bax蛋白含量，并采用TUNEL法观察细胞凋亡。结果大鼠体外循环停循环后的不同时点白细胞（PMN）表面的黏附分子CD11b表达均明显升高，EA组PMN表面的黏附分子CD11b的表达明显下降。CPB后大鼠心肌细胞Bcl-2和BaxmRNA表达明显增强，EA组凋亡相关基因BaxmRNA表达明显降低，Bcl-2mRNA表达明显增加。CPB组心肌组织Bcl-2和Bax蛋白含量显著增高，EA组Bax蛋白表达明显降低，Bcl-2蛋白表达明显增加。CPB组心肌缺血再灌注损伤后心肌细胞凋亡数明显增加，EA组心肌凋亡细胞数与心肌缺血组相比明显减轻。结论电针内关穴可通过抑制凋亡，减轻体外循环下心肌组织的病理损伤，抑制炎症细胞的黏附，从而产生心肌保护作用。     

烧伤延迟复苏大鼠肝脏损伤

目的 研究延迟复苏大鼠肝脏损伤情况。方法 ＳＤ大鼠３０％Ⅲ度烧伤后,随机分成烧伤组、早期复苏组、延迟复苏组。伤后９ｈ取肝组织,测定脏器血管通透性、组织含水量、Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活性和Ｃａ＾２＋－Ｍｇ＾２＋－ＡＴＰ酶活性,髓过氧化物酶（ＭＰＯ）活性和一氧化氮（ＮＯ）代谢产物量。结果 与烧伤组与早期复苏组相比,伤后９ｈ延迟复苏组大鼠肝脏的血管通透性和含水量明显增高,Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活     

川芎嗪对烫伤大鼠早期肝脏损伤的保护作用

目的:探讨川芎嗪在烫伤大鼠早期肝脏损伤中的作用及其机制。方法:采用30%TBSAⅢ度烫伤大鼠模型,将SD大鼠随机分为对照组(C组)、单纯烫伤组(烫伤组,S组)和川芎嗪处理组(模型建立成功即刻腹腔内注射川芎嗪注射液,20mg/kg,L组),每组10只。伤后24h、48h分别检测3组大鼠血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)活性、游离脂肪酸(FFA)含量,及肝组织中三磷酸腺苷(ATP)的含量、线粒体肉碱脂酰转移酶I(CAT I)的活性、超氧化物歧化酶(SOD)活性、丙二醛(MDA)的含量。结果:与C组比较,S组在伤后24h、48h血清中ALT和AST的活性、FFA含量、肝组织中MDA含量均明显升高,同时ATP的含量、CAT I酶的活性、SOD活性明显降低(P<0.01);与S组比较,L组在伤后24h、48h均能明显降低ALT、AST活性和FFA和MDA的含量(P<0.01);及提高肝组织ATP的含量、线粒体ATP酶的活性、SOD活性(P<0.01)。结论:川芎嗪对烫伤大鼠早期肝脏起保护作用,其机制可能是改善脂源性能量的利用。     

体外循环心脏直视手术中乌司他丁对肝脏的保护作用

目的：探讨乌司他丁（ulinastatin，UTI）在体外循环（camiopulmonary bypass，CPB）心脏手术期间对肝脏的作用，为乌司他丁在体外循环心脏手术中的应用提供临床依据。方法：30例体外循环心脏直视手术患者随机分为实验组（A组，n=15）和对照组（B组，n=15）。A组预冲液中加入UTI 1．5万U／kg，B组不加UTI。分别于术前、主动脉及心脏插管完毕后30min、开放升主动脉后1h、6h及术后24h，从中心静球插管采集血标本，典5次。放免法检测血中TNR-α、IL-6、IL-8含量，全自动生化分析仪检测血中丙氨酸氨基转移酶（ALT）、总胆红素（TB）水平变化。结果：两组患者血中TNF-α、IL-8、IL-6、ALT、TB在插管30min后避渐升高，A组术中及术后各时段各项指标均低于B组，且两组同时段有显著差异（P〈O．05或P〈0．01）。结论；乌司他丁在体外循环心脏直视手术期间对肝脏具有保护作用。     

银杏叶提取物对大鼠肝脏缺血再灌注损伤的保护作用及对凋亡的影响

肝外科实践中常常需要阻断肝门血管以完成复杂的肝脏手术，如肝破裂修补术、肝移植术等。阻断入肝血流后导致的肝脏缺血再灌注（IR）损伤受到肝外科广泛关注。银杏叶提取物（EGB）由于在心、脑血管疾病等方面的作用广泛用于临床治疗。而EGB对肝IR后损伤是否有保护作用研究较少。本实验通过研究EGB对大鼠肝脏缺血再灌注损伤（IRI）中对肝细胞凋亡的影响来探讨EGB对大鼠肝脏IRI的保护作用及可能的机制。     

Lung injury after cardiopulmonary bypass

Pulmonary injury during cardiopulmonary bypass is common as patient factors (smoking, pain, pneumonia) and the effects of cardiopulmonary bypass combine to compromise lung function after cardiac surgery. Lung injury follows the propagation of an inflammatory response involving cytokines, complement, neutrophils, monocytes, activated endothelial cells and platelets. Neutrophils sequester in the lung in response to chemotactic agents and release injurious oxygen free radicals and specific enzymes resulting in widespread pulmonary injury. To alleviate this lung injury a number of possible interventions exist. Off pump surgery may reduce the degree of systemic inflammation but respiratory impairment still occurs and the clinical advantage is uncertain. The use of leukocyte filtration can attenuate the acute inflammatory response with encouraging though variable results. Aprotinin, Pentoxyfilline, Nitric oxide, Aspirin and other agents have shown benefits in lung function after cardiopulmonary bypass induced lung injury. Given the magnitude and diversity of the inflammatory response to cardiopulmonary bypass many possible interventions exist to attenuate lung injury resulting from extracorporeal circulation. Immediate clinical benefits are likely to result from successful amelioration of the processes involved.     

Effects of sesame oil on oxidative stress and hepatic injury after cecal ligation and puncture in rats

Oxidative stress is known to be involved in the development of organ failure and death in sepsis. Sesame oil attenuates oxidative stress induced by endotoxin; however, whether sesame oil is still effective in rats with sepsis has never been investigated. The aim of the present study was to determine the effect of sesame oil on oxidative stress-associated hepatic injury in cecal ligation and puncture-induced rats with sepsis. We examined the effect of sesame oil (4 mL/kg daily for 1 week) on lipid peroxidation, hydroxyl radical, superoxide anion, and nitrite levels in rats with sepsis. In addition, hepatic injury was also assessed by blood biochemistry. Sesame oil significantly decreased lipid peroxidation and serum nitrite levels, but affected neither superoxide anion nor hydroxyl radical in cecal ligation and puncture-treated rats. Furthermore, sesame oil significantly attenuated cecal ligation and puncture-induced hepatic injury in rats. Nevertheless, oxidative stress and hepatic injury were not affected by corn oil or mineral oil in rats with sepsis. Thus, attenuation of oxidative stress and hepatic injury may be associated with inhibition of nitric oxide in sesame oil-associated protection in rats with sepsis.     

Sesamol delays mortality and attenuates hepatic injury after cecal ligation and puncture in rats: role of oxidative stress

Sesame oil potently protects rats against sepsis, and sesamol appears to be the protective ingredient in sesame oil. The aims of the present study were to examine the effects of sesamol on mortality and reactive oxygen species-associated liver injury in Wistar rats with cecal-ligation-and-puncture-induced sepsis (septic rats). After sepsis was induced, sesamol was administered every 6 h. The survival rate was determined during the ensuing 48 h. Hepatic injury was assessed using blood biochemistry and histological examination. Hepatic oxidative stress was assessed by determining the levels of liver lipid peroxidation, hydroxyl radical, and superoxide anion generation, and nitric oxide production 12 h after cecal ligation and puncture. Inducible nitric oxide synthase expression was also determined. Sesamol delayed mortality and attenuated hepatic injury in septic rats. Hepatic lipid peroxidation, hydroxyl radical, and superoxide anion levels were significantly lower in sesamol-treated septic rats. Furthermore, sesamol inhibited the production of nitrite and the expression of inducible nitric oxide synthase in the liver in septic rats. Therefore, sesamol may delay mortality and attenuate oxidative stress-associated liver injury by inhibiting the production of nitric oxide, at least partially, in septic rats.     

Lung injury after cardiopulmonary bypass: Alternative treatment prospects

Although the lung injury caused by cardiopulmonary bypass (CPB) has been extensively investigated, the incidence and mortality of lung injury after CPB remain a prominent clinical problem. The poor outcome has been attributed to multifactorial etiology, including the systemic inflammatory response and ischemia reperfusion (I/R) injury during CPB. Lung injury after CPB is a complex pathophysiological process and has many clinical manifestations of mild to severe disease. Which is associated with prognosis. To alleviate this lung injury, interventions that address the pathogenesis are particularly important. This review summarizes the pathogenesis, mechanism and treatment options of lung injury after CPB, such as lung protection with intralipid.     

The protective effect of sesamol against mitochondrial oxidative stress and hepatic injury in acetaminophen-overdosed rats

An acetaminophen (APAP) overdose induces oxidative stress and acute hepatic injury or even death. We investigated the prophylactic effect of sesamol (SM) on mitochondrial oxidative stress, hydroxyl-radical-generated lipid peroxidation, and hepatic injury in APAP-overdosed rats. Six male Wistar rats (APAP group) were given only oral APAP (1,000 mg/kg) to induce mitochondrial oxidative-stress-associated hepatic injury, and another six (ASM group) were given the same dose of oral APAP, and then, immediately afterward, were injected with SM (10 mg/kg, i.p.), to assess its prophylactic effects. In the APAP group, APAP had significantly increased the levels of 1) serum aspartate transaminase and alanine transaminase, 2) centrilobular necrosis, 3) ferrous ions, 4) hydrogen peroxide, 5) hydroxyl radicals, and 6) lipid peroxidation, and decreased 7) mitochondrial aconitase activity in the rats' liver tissue 24 h later. In the ASM group, SM had prevented significant rises in the levels of 1) to 6) and a significant decrease (7). Therefore, we hypothesize that the protective effect of SM in APAP-overdosed rats is associated with maintaining the mitochondrial aconitase activity, ferrous ions (Fe2+), and hydrogen peroxide levels and inhibiting hydroxyl-radical-associated lipid peroxidation and hepatic injury.     

右美托咪定对心肺复苏大鼠氧化应激反应的保护作用

目的探讨右美托咪定注射液(DEX)对大鼠心肺复苏(CPR)后氧化应激反应的保护作用及其机制。方法36只SD雄性大鼠随机分为3组,每组12只。假手术组(S组),仅给予麻醉、气管插管和血管穿刺,不行窒息和心肺复苏;心肺复苏组(CPR组)和右美托咪定干预组(DEX组),均采用窒息法制备大鼠心搏骤停模型,行标准心肺复苏,待自主循环恢复(ROSC)后,DEX组即刻给予DEX 50μg/kg缓慢静脉注射,CPR组即刻给予与DEX等量的生理盐水注射。分别在基础状态下及ROSC后3 h、12 h、24 h抽取大鼠动脉血,并测定丙二醛(MDA)水平和超氧化物岐化酶(SOD)活性。结果 S组大鼠均存活至24 h;CPR组大鼠经复苏后有11只恢复自主循环,其中9只存活至24 h;DEX组大鼠经复苏后有10只恢复自主循环,且均存活至24 h。3组大鼠在基础状态下MDA水平和SOD活性差异无显著性(P0.05)。CPR和DEX组大鼠复苏后其MDA水平逐渐增高,而SOD活性逐渐减低,均于12 h达到最高(低)值。DEX组大鼠在复苏后3 h、12 h、24 h其MDA水平明显低于CPR组大鼠[3 h:(5.56±1.19)nmol/ml比(8.54±1.44)nmol/ml,12 h:(8.13±1.93)nmol/ml比(13.60±2.97)nmol/ml,24 h:(6.36±1.17)nmol/ml比(9.82±1.38)nmol/ml],差异均有统计学意义(均P0.05);DEX组大鼠在复苏后3 h、12 h、24 h其SOD活性明显高于CPR组大鼠[3 h:(152.50±13.59)U/ml比(135.09±12.97)U/ml,12 h:(124.30±14.58)比(95.45±17.79)U/ml,24 h:(132.50±11.61)比(106.63±9.34)U/ml],差异均有统计学意义(均P0.05)。结论右美托咪定能够减轻大鼠心肺复苏后氧化应激反应,这一作用可能是通过抑制MDA产生、上调SOD活性实现的。     

心肺旁路后急性肾损伤的防治

心肺旁路术后急性肾损伤(acute kidney injury,AKI)有较高的发病率,增加患者住院时间和死亡风险.判断心肺旁路AKI的危险因素和早期诊断可能给心肺旁路手术患者带来益处,一旦患者发生AKI应该尽早实施干预,目前对该类患者进行肾替代治疗的方式、剂量尚没有统一,应该遵从个体化原则.