内皮素-1与肝脏缺血再灌注损伤的实验研究

目的：探索内皮素－1（ET－1）在肝脏血再灌注损伤中的作用。方法：选择雄性Wistar大鼠80只,分为正常对照组、缺血再灌注组1生理盐水组和ET－1抗体组、观察肝脏缺血60min再灌注3h后血浆ET－1、丙氨酸转氨酶（ALT）、透明质本酸（HA）、以及肝组织中ET－1和丙二醛（MDA）含量的变化,并观察肝组织病理学变化,同时,在缺血再灌注组选择第1、3、6、12和24h时相点观察ET－1的变化规律。结果：肝脏缺血再灌注后,血浆和肝组织中ET－1,血浆HA`ALT肝组织中MDA显著升高,而ET－1抗体组血浆ET－1、HA、ALT与缺血再灌注组相比显著降低（P＜0．01,P＜0．05）,同时,肝组织的瘀血程度和损伤程度显著改善。结论ET－1参与了肝脏缺血再灌注损伤,这种损伤与肝脏微循环障碍有关。     

EGCG对大鼠肾脏缺血再灌注损伤的保护作用

目的研究表绿茶活性成分没食子儿茶素-3-没食子酸酯（epigallocatechin gallate，EGCG）对大鼠肾脏缺血再灌注损伤是否具有保护作用。方法将12只Lewis大鼠随机分为2组：（1）实验组大鼠7只，于肾缺血后的再灌注期将10mg／kg的EGCG置于2ml生理盐水中静脉注射；（2）对照组大鼠5只，于肾缺血后的再灌注期静脉注射2ml生理盐水。2h后处死动物，收集血液和肾脏标本，行血肌酐（Cr）、尿素氮（BUN）、肾组织超氧化物歧化酶（SOD）和脂质过氧化产物丙二醛（MDA）含量测定，并进行组织病理和超微病理检查。结果实验组大鼠血Cr和BUN水平明显低于对照组（P〈0.05），肾组织中SOD活性较对照组明显升高（P〈0．01），肾组织脂质过氧化产物MDA的含量较对照组明显降低（P〈0．01）。病理学检测表明实验组大鼠肾小管周围毛细血管内未见淤血，肾小管上皮细胞变性及线粒体的损伤减轻。结论EGCG对大鼠肾脏缺血再灌注损伤具有保护作用。     

大鼠肾脏缺血再灌注损伤与重组成骨蛋白-1的关系

目的探讨鼠重组成骨蛋白1(rOP1)在大鼠肾脏缺血再灌注损伤过程中对氧自由基、细胞凋亡的影响及其对肾脏的保护作用。方法观察静脉应用rOP1250μg/kg体重,大鼠肾脏缺血60min,再灌注24h后,血浆超氧化物歧化酶(SOD)、脂质过氧化物丙二醇(MDA)、内皮素1(ET1)的变化,及其对肾脏细胞凋亡的影响。结果rOP1组和缺血再灌注组血浆SOD分别是(108±20)和(86±11)KNU/L,MDA分别是(8.90±0.49)和(11.70±0.81)μmol/L,ET1分别是(130±39)和(179±45)ng/L,rOP1组SOD水平显著性高于缺血再灌注组(P<0.05),而MDA和ET1水平显著性低于缺血再灌注组(P<0.05)。两组肾脏细胞凋亡指数分别是(5.72±3.08)%和(8.85±3.52)%,rOP1组显著性低于缺血再灌注组(P<0.01)。上述两组肾脏的的Miller’s评分分别是(2.0±0.3)和(3.4±0.5),rOP1组显著低于缺血再灌注组(P<0.01)。结论rOP1减轻氧自由基对肾脏缺血再灌注损伤,降低肾脏细胞凋亡指数,对肾脏缺血再灌注损伤具有保护作用。     

红景天甙对大鼠肾脏缺血再灌注损伤的保护作用

目的探讨红景天甙对大鼠肾脏缺血再灌注损伤（IRI）的预防和保护作用。方法将32只健康成年SD大鼠随机分成正常对照组、假手术组、缺血再灌注组和红景天甙组4组，每组8只。缺血再灌注组和红景天甙组分别制作肾脏缺血再灌注模型，红景天甙组予以红景天甙预处理。检测血中尿素氮（BUN）和肌酐（Scr）及肾脏中超氧化物歧化酶（SOD）、丙二酰二醛（MDA）和钠钾ATP酶（Na^＋-K^＋ATPase）含量，并用光镜和电镜观察肾脏组织形态学变化。结果红景天甙组血清BUN和Scr水平、肾皮质MDA含量较缺血再灌注组显著降低（P〈0．01），而肾皮质中SOD和Na^＋-K^＋ATPase含量与缺血再灌注组相比显著升高（P〈0．01）；肾组织光镜和电镜观察均见缺血再灌注组肾小球和肾小管上皮细胞损伤明显，而红景天甙组肾小球及肾小管仅见轻微损伤。结论红景天甙能有效降低大鼠肾脏缺血再灌注损伤（IRI），对肾脏IRI有明显的预防和保护作用，为临床上肾脏IRI提供新的预防和治疗思路。     

莲子提取物对大鼠急性肾缺血再灌注损伤的影响研究

目的：研究莲子提取物对大鼠急性肾缺血再灌注损伤的影响,并初步探讨其作用机制,为将来应用于临床提供理论依据。方法：选用健康雄性SD大鼠30只随机分为三组：假手术组（ Sham组）、缺血再灌注损伤组（ RIRI组）、莲子提取物给药组（ LE组）。再灌注24 h 后,检测大鼠血清中丙二醛（ MDA ）、超氧化物歧化酶（ SOD ）、血清肌酐（ Scr ）和尿素氮（ BUN）,肾组织中MDA含量和谷胱甘肽过氧化物酶（ GSH-Px）的活性,并采用肉眼和光镜下观察肾脏组织病理学切片以及肾小管计分等病理变化。结果：与肾脏缺血再灌注组相比,莲子提取物给药组大鼠血清中MDA、 Scr、 BUN含量均显著降低（P〈0.01）,血清中SOD含量升高（P〈0.01）、肾小管计分明显降低（P〈0.01）,肾组织中MDA含量降低（P〈0.01）、GSH-Px活性增强（P〈0.01）。结论：莲子提取物对急性肾缺血再灌注损伤具有保护作用,其作用机制可能与抗自由基损伤和减轻脂质过氧化、抗血栓形成有关。     

等容血液稀释和川芎嗪在兔心肌缺血再灌注损伤中的抗氧化作用

目的：研究6％羟乙基淀粉（6％hydroxyethyl starch,6%HES)急性等容血液稀释和川芎嗪注射液对兔心肌缺血再灌注损伤的保护作用。方法：32只家兔随机分为四组，每组8只，I组为对照组；Ⅱ组为稀释组；Ⅲ组为川芎嗪组；Ⅳ组为稀释加川芎嗪组。观察在急性心肌缺血45min及再灌180min状态下血浆过氧化物歧化酶（SOD）活性、丙二醛（MDA）含量的变化及心肌超微结构改变。结果：缺血后，I组血浆SOD活性明显降低（P＜0．05）；Ⅱ，Ⅲ，Ⅳ组血浆SOD活性亦降低，但差异无显著性。再灌后，I组血浆SOD活性进一步降低（P＜0．05）。I组MDA含量在缺血后及再灌后升高（P＜0．05），Ⅱ，Ⅲ，Ⅳ组升高程度较I组轻。心肌细胞超微结构可见I组结构破坏严重，Ⅱ，Ⅲ组结构破坏均较轻，Ⅳ组结构基本接近正常。结论：6％HES等容血液稀释和川芎嗪对心肌缺血再灌注损伤均有保护作用，两者合用保护作用更为显著。     

益肾排石中药保护高能冲击波致肾损伤的实验研究

目的：探讨益肾排石中药对高能冲击波致肾损伤的保护作用。方法：将家兔30只随机分为两组，中药组和生理盐水对照组各15只，于高能冲击波致兔肾损伤模型，测定不同时间血浆，肾组织浆浆内皮素（ET－1），超氧化物歧化酶（SOD）、丙二醛（MDA）变化及肾组织病理改变。结果：冲击波肾损伤后血浆中ET－1、血清中MDA值及组织均浆中ET－1、MDA值显著升高（P＜0．05），血浆及组织匀浆中SOD显著降低（P＜0．05）；而中药治疗组血浆中ET－1、MDA及组织均浆中ET－1、MDA峰值显著低于对照组（P＜0．05），血浆及组织匀浆中SOD值高于对照组（P＜0．05），且病理检查较对照组损伤轻。结论：益肾排石中药对高能冲击波致肾损伤具有保护作用。     

纳洛酮对大鼠急性缺血性肾衰的保护作用

为探讨纳洛酮（NAL）对肾脏缺血再灌注损伤中的保护作用，利用大鼠肾脏缺血再灌注致急性缺血性肾功能衰竭（肾衰）模型，观察NAL对肾缺血再灌注后血中丙二醛（MDA）、超氧化物歧化酶（SOD）及肾组织中Na+、K+－ATP酶和Ca2+－ATP酶的影响，并观察组织病理学变化。结果缺血60min再灌注后，血MDA含量明显升高，SOD活力明显降低，肾组织Na+、K+－ATP酶和Ca2+－ATP酶活力均显著降低。用NAL（Ⅰ组为2mg／kg，Ⅱ组为4mg／kg）后，MDA显著下降，SOD和Na+、K+－ATP酶及Ca2+－ATP酶均明显升高，且有量效关系。组织病理学检查显示应用NAL后肾小管上皮细胞的损伤明显减轻，NAL－Ⅱ组明显好于NAL－Ⅰ组。认为NAL对急性缺血性肾衰有一定的保护作用。     

缺血后处理对肝脏缺血再灌注中肝窦内皮细胞损伤的保护作用

目的探讨缺血后处理对肝脏缺血再灌注中肝窦内皮细胞损伤的保护作用.方法建立大鼠局部肝脏缺血再灌注模型,将24只健康雄性Wistar大鼠随机分为假手术、缺血再灌注、缺血后处理3组,以缺血再灌前、反复多次的短暂预再灌、停灌作后处理,观察各组血浆肝酶及透明质酸(HA)水平变化和肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、内皮素-1(ET-1)含量,并行肝组织病理形态学检查.结果与缺血再灌注组相比,缺血后处理组肝酶的漏出、血浆HA水平及肝组织中MDA、ET-1的含量明显降低(P＜0.01),而SOD活性则显著升高(P＜0.01),肝组织病理学损伤亦明显减轻.结论缺血后处理可通过抑制再灌注后氧自由基的过量生成而保护肝窦内皮细胞,减轻肝脏缺血再灌注损伤.     

山莨菪碱对肝脏缺血再灌注损伤的保护作用

目的 探讨山莨菪碱对肝脏缺血再灌注损伤的保护作用。方法 将雄性Wistar大鼠制成肝脏缺血再灌注模型,随机分为正常对照组、缺血再灌注组、生理盐水组和山莨菪碱组,观察肝脏缺血60min再灌注1、3、6、12及24h后血浆和／或肝组织中内皮素－1（ET－1）、透明质酸（HA）、丙氨酸转氨酶（ALT）、丙二醛（MDA）和再灌注1h后肝细胞内游离Ca^2 ([Ca^2 ]i)、ATP含量变化以及肝组织病理学改变。结果 肝脏缺血再灌注后血浆和／或肝细胞中ET－1、HA、ALT、MDA和肝细胞内[Ca^2 ]u含量均显著升高,而肝组织中ATP含量明显降低;肝脏缺血再灌注前应用山莨菪碱2.0mg/kg者,血浆HA和肝细胞内[Ca^2 ]i含量明显降低,肝组织中MDA也有不同程度的降低,而肝组织中ATP含量明显升高,同时肝酶的漏出减少,肝组织病理学损害明显减轻。结论 山莨菪碱对肝脏缺血再灌注损伤具有保护作用。     

黄芪对肾缺血再灌注损伤的保护作用

目的 探讨黄芪注射液对肾脏缺血再灌注损伤的影响。方法 观察黄芪注射液对肾缺血再灌注损伤大鼠血浆超氧化物歧化酶（ＳＯＤ）,脂质过氧化产物丙二醇（ＭＤＡ）,内以素－１（ＥＴ－１）,一氧化氮（ＮＯ）变化及肾组织病理改变。结果 黄芪治疗组血浆ＥＴ０－１,ＭＤＡ水平较缺血再灌注组显著下降,ＳＯＤ显著升高,且病理改变较轻。结论 黄芪对肾脏缺血再灌注损伤具有保护作用。．     

内皮素1单抗对肝移植缺血再灌注损伤中肝细胞凋亡的影响

目的探讨细胞凋亡在移植肝缺血再灌注损伤中的作用及内皮素1(ET-1)单克隆抗体对细胞凋亡的影响。方法应用ET-1单抗灌注移植肝，检测血浆与肝组织中ET-1，检测肝功能，测定移植肝组织的MDA及细胞凋亡：结果移植肝再灌注后血中ET-1，谷丙转氨酶(ALT)和肝组织中ET-1与MDA均明显升高，肝细胞凋亡明显增加；应用ET-1单抗后，血中ET-1，ALT和肝组织中ET-1及MDA均降低，肝细胞凋亡亦明显减少。结论ET-1单抗可通过减轻移植肝脂质过氧化反应的作用，从而减少肝细胞凋亡，起减轻到肝细胞损伤，从而保护移植肝。     

丙泊酚对大鼠急性肾缺血再灌注损伤的影响

目的 探讨丙泊酚预处理对急性肾缺血再灌注损伤(acute renal ischemia reperfusion injury ,ARIRI)的保护作用及其机制.方法 采用完全随机研究设计(randomized controlled trial,RCT),健康近交系清洁级的雄性SD大鼠63只,随机分为3组:假手术组(A组)、缺血再灌注组(B组)、丙泊酚预处理组(C组),每组21只SD大鼠.采用切除右侧肾,用无损伤微动脉夹夹闭左侧肾蒂60分钟后解除阻断,建立大鼠急性肾缺血再灌注损伤模型.用24号套管针股静脉穿刺置管,实验过程中各组使用微量注射泵注入不同注射液.分别于手术前15分钟、再灌注后2小时、24小时留取血和肾组织标本同时处死大鼠,检测血清尿素氮(BUN)、肌酐(Cr)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及观察这三个时点肾组织的病理学改变.结果 丙泊酚预处理组各个时点的肾组织病理学变化均轻于缺血再灌注组.缺血再灌注组中血清BUN、Cr、MDA和TNF-α水平增加均高于丙泊酚预处理组(p＜0.05),丙泊酚预处理组血清SOD、IL-6水平均高于缺血再灌注组(p＜0.05).结论 丙泊酚预处理组血清BUN、Cr、MDA、TNF-α、SOD、IL-6水平与缺血再灌注组均有统计学差异.结果 表明丙泊酚能减少氧自由基释放,抑制和减少炎症反应,在急性肾缺血再灌注损伤能起到保护肾脏的作用.     

Protective effects of ligustrazine on ischemia-reperfusion injury in rat kidneys

To investigate the protective effects of ligustrazine on renal ischemia-reperfusion injury, the influence of ligustrazine injection on plasma superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1), as well as changes of morphology of renal tubules, were studied in rat kidney models with ischemia-reperfusion injury. The results showed that in the group treated with ligustrazine, the plasma SOD level was significantly higher than that of the control group (P < 0.05), but levels of plasma MDA and ET-1 and the pathological grading of injured renal tubules were significantly lower than those in the control group (P < 0.05). These findings suggest that ligustrazine has protective effects against ischemia-reperfusion injury in rat kidneys.     

川芎嗪在骨骼肌缺血再灌注损伤中的作用

目的　探讨中药川芎嗪在骨骼肌缺血再灌注损伤中有无保护作用。方法　健康成年家兔14只 ,随机分对照组、实验组 ,每组 7只。应用家兔肢体缺血再灌注损伤动物模型 ,在恢复血流再灌注当时 ,实验组静脉输注川芎嗪注射液 ,对照组静脉输注 0 9%生理盐水。测定缺血前、缺血后、再灌注后血浆丙二醛 (MDA)、乳酸脱氢酶 (LDH)及超氧化物歧化酶 (SOD)的含量。制备骨骼肌标本进行光镜及透射电镜观察。结果　实验组在恢复血流并注射川芎嗪后 1小时 ,其血浆MDA、LDH的含量较对照组明显降低 (P <0 0 1) ,而SOD较对照组明显升高 (P <0 0 1)。光镜及电镜下观察可见实验组骨骼肌损害轻于对照组。结论　实验表明中药川芎嗪对骨骼肌缺血再灌注损伤有保护作用     

乌司他丁对肝脏肿瘤切除术患者肝脏缺血-再灌注损伤的保护作用

目的观察乌司他丁对肝脏肿瘤切除术患者肝脏缺血-再灌注损伤的保护作用。方法选择32例ASAⅠ～Ⅲ级拟行肝脏肿瘤切除术的患者,随机均分为乌司他丁组(U组)和对照组(C组)。U组:乌司他丁12000U/kg加在生理盐水50ml中,麻醉诱导后切皮前经颈内静脉泵入;C组:注入等量的生理盐水。在切皮时(T1)、缺血后10min(T2)、再灌注10min(T3)、30min(T4)、1h(T5)、术后1d(T6)、2d(T7)抽取静脉血测定血浆中谷草转氨酶(AST)、谷丙转氨酶(ALT)、超氧化物歧化酶(SOD)活性,丙二醛(MDA)水平、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)浓度。结果与T1时比较,T3～T6时两组的AST、ALT活性、MDA水平、IL-1β、IL-6、TNF-α浓度均明显升高;SOD活性明显降低(P<0.05)。与C组比较,T2～T7时U组的AST和ALT活性明显降低;T3～T5时MDA水平、IL-1β、IL-6和TNF-α浓度均明显降低;T3～T5时SOD活性明显升高(P<0.05)。结论乌司他丁能抑制氧自由基生成和炎症因子的释放,对肝脏缺血-再灌注损伤具有保护作用。     

Effect of ligustrazine on ischemia-reperfusion injury in murine kidney

INTRODUCTION: Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal transplantation. It contributes to acute rejection and chronic allograft dysfunction. Studies have shown that Ligustrazine, a purified and chemically identified component of a Chinese herbal remedy, is a potent blocker of vasoconstriction and has strong effects to scavenge oxygen free radicals. Since warm I/R is potentially more damaging than cold storage, we investigated the possible protective effect of Ligustrazine on warm I/R in mice. METHODS: Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of left renal ischemia. Group I were sham-operated animals; group II, nontreated animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde (MDA)level, and superoxide dismutase (SOD) were determined as well as examining the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1. RESULTS: I/R produced a six fold increase in creatinine and urea nitrogen levels in group II. Ligustrazine halved the increase, as well as attenuated the necrosis and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P < .01). CONCLUSION: These findings suggest that Ligustrazine reduces the renal dysfunction associated with warm I/R of the kidney.     

Hyperbaric Oxygen Therapy Alleviates Oxidative Stress and Tissue Injury in Renal Ischemia/Reperfusion Injury in Rats

Hyperbaric oxygen (HBO) therapy has been shown to attenuate renal ischemia/reperfusion (I/R) injury in rats, when applied in the early reperfusion period. The aim of this study was to elucidate possible beneficial effects of HBO therapy on renal I/R injury, when applied 24 h after ischemia. Rats were randomized into three groups: (1) control group (n = 20), (2) I/R group (n = 20), and (3) I/R + HBO group (n = 20). Renal I/R injury was created by interrupting renal blood flow for 30 min with a non-traumatic vascular clamp. HBO therapy was administered 24 h after I/R injury and continued for 5 days. At the end of the study, rats were sacrificed under anesthesia, blood was drawn, and right kidneys were harvested for analysis. Renal I/R injury increased serum and tissue malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. HBO therapy attenuated MDA levels by increasing SOD and GPx activities. HBO therapy also prevented neutrophil infiltration and tissue injury in kidneys. Taken together, HBO therapy has been found to be effective in the delayed period of I/R injury.     

Effect of ligustrazine on chronic allograft nephropathy in rats

OBJECTIVES: Our previous study demonstrated that Ligustrazine reduced renal dysfunction associated with ischemia-reperfusion injury in mice. In this study, we investigated whether Ligustrazine herbal injection had any preventive and therapeutic effectiveness against chronic allograft nephropathy in rats. METHODS: Male Lewis rats that received left renal grafts from male Fisher 344 rats were randomly divided into five groups: group A only received cyclosporine (CsA; 10 mg.kg(-1).d(-1)) every day. Groups B, C, and D received low-dose Ligustrazine (50 mg.kg(-1).d(-1))+CsA (10 mg.kg(-1).d(-1)); high-dose Ligustrazine (100 mg.kg(-1).d(-1))+CsA (10 mg.kg(-1).d(-1)); and CsA (10 mg.kg(-1))+mycophanolate mofetil (10 mg.kg(-1).d(-1)), respectively. Group E was an isografted group (Fisher 344 to Fisher 344). Grafts were preserved in 4 degrees C University of wisconsin solution for 1 hour prolonged cold ischemia. All recipient animals were unilaterally right nephrectomized. Serum creatinine (Scr), blood urea nitrogen (BUN), urinary protein, kidney malondialdehyde (MDA) level, and superoxide dismutase (SOD) were determined, as well as examining kidney histology with immunohistochemistry for Bcl-2, and ICAM-1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested to show whether Ligustrazine has side effects. RESULTS: Compared with group E, ischemia and rejection produced a ninefold increase in GSR and Banff score, as well as significant increases of Scr, BUN, and urinary protein levels in group A. High doses of Ligustrazine significantly slowed the increase (P<.01). Ligustrazine also decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated posttransplantation, especially in the Ligustrazine-treated group (P<.01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P<.01). Furthermore, there was little difference in ALT/AST between the Ligustrazine-treated and the isograft group. CONCLUSION: These findings suggested that Ligustrazine could postpone chronic renal allograft dysfunction associated with cold ischemia injury and chronic allograft rejection but had no evident hepatic side effects.