中叶素对糖尿病大鼠缺血再灌注心肌细胞凋亡的影响

目的观察中叶素(IMD)对糖尿病大鼠缺血再灌注心肌细胞凋亡的影响,并探讨其可能的作用机制。方法健康雄性SD大鼠74只,给予适应性饲养一周后,随机分为糖尿病组(50只)和非糖尿病组(24只),非糖尿病组给予枸橼酸缓冲液腹腔注射,糖尿病组通过腹腔注射链脲佐菌素建立糖尿病模型。阻断大鼠左冠状动脉前降支制备心肌缺血再灌注损伤模型。非糖尿病组24只大鼠随机分为对照组和缺血再灌注组(NIR组),糖尿病组50只大鼠成功建立糖尿病模型为36只,随后随机分为糖尿病对照组、糖尿病缺血再灌注组(DIR组)、IMD组,每组12只。光镜观察心肌细胞的形态变化,电镜观察心脏超微结构,TUNEL法检测心肌细胞凋亡率,Western blot检测凋亡相关蛋白Caspase-3、Bcl-2和Bax的蛋白表达量。结果光镜下可观察到NIR组、DIR组心肌细胞损伤变化比相应对照组更趋于严重,IMD组心肌细胞变性坏死的程度较糖尿病缺血再灌注组明显减轻。电镜下NIR组和DIR组心肌细胞损伤较相应对照组严重,IMD组心肌组织的超微结构特别是线粒体损伤与DIR组比较明显减轻。NIR组和DIR组心肌细胞凋亡率明显高于相应的对照组(P0.05),IMD组心肌细胞凋亡率则较NIR组明显减少(P0.05)。NIR组和DIR组Caspase-3、Bax和Bcl-2的蛋白表达量均与相应对照组比较差异有统计学意义(P0.05),IMD组心肌组织Caspase-3、Bax和Bcl-2的蛋白表达量与DIR组相比差异也具有统计学意义(P0.05)。结论IMD对糖尿病大鼠心肌缺血再灌注损伤具有保护作用,其保护作用可能与IMD减少心肌细胞凋亡有关。     

胰腺血运阻断安全性的实验研究

目的探讨大鼠胰腺不同血运阻断时间的损伤程度,确定合适的没有明显缺血再灌注损伤的大鼠胰腺热缺血时间.方法将成年雄性SD大鼠60只随机分为5组:A组,正常对照组;B组,10 min缺血组;C组,20 min缺血组;D组,30 min缺血组;E组,60 min缺血组,每组各12只.通过钳闭大鼠腹腔干和肠系膜上动脉,建立大鼠胰腺的缺血再灌注损伤模型,对不同血运阻断时间的胰腺组织进行光、电镜检查和相关血清丙二酰二醛(MDA)、超氧化歧化酶(SOD)、一氧化氮(NO)、淀粉酶(AMS)等生化指标检测.结果不同热缺血时间的大鼠胰腺组织的病理变化及其MDA、SOD、NO、AMS等生化指标间均存在差异,B组无明显缺血再灌注损伤,C组出现缺血再灌注损伤,D组有显著的缺血再灌注损伤,E组有严重的缺血再灌注损伤.结论胰腺血运阻断时间不能超过20 min,最好不超过10 min.     

血管紧张素ⅡⅠ型受体阻断剂抑制大鼠缺血-再灌注模型心肌细胞凋亡

目的观察血管紧张素ⅡⅠ型受体阻断剂losartan对大鼠心肌缺血-再灌注模型心肌细胞凋亡及凋亡相关蛋白P53和Bcl-2表达的影响。方法Wistar大鼠随机分为三组(1)假手术组(5只);(2)缺血-再灌注组(6只)结扎左冠状动脉45min,再灌注4h;(3)losartan组(6只)缺血前15min和再灌注1h分别静脉注射losartan10mg/kg。采用TUNEL和DNA电泳方法检测心肌细胞凋亡,免疫组织化学方法检测心肌组织P     

大鼠心肌缺血-再灌注模型的心电图变化

目的 研究大鼠心肌缺血再灌注模型的心电图变化.方法 将23只雄性大鼠按电脑随机数字表法分为假手术组及缺血再灌注损伤组.缺血再灌注损伤组结扎左前降支35 min,再灌注120 min;而假手术组仅给予左前降支过线不结扎血管.采用氯化三苯基四氮唑(tetrazolium chloride,TTC)染色法检测大鼠缺血再灌注心...     

乌司他丁在肺缺血再灌注损伤中的保护作用

目的 :研究乌司他丁 (UTI)在肺缺血再灌注损伤中的保护作用。方法 :采用新西兰大白兔 32只肺缺血再灌注模型 ,均分为 4组 :对照组 (Ⅰ组 ) ,Ⅱ组缺血前 30min用UTI 0 .6万U/kg ,Ⅲ组 :缺血前 30min用UTI 1.2万U/kg ,Ⅳ组 :缺血前 30min及再灌注初分别给药UTI 1.2万U/kg。于夹闭左肺门前和开放左肺门 30min后 ,分别取左、右房血测白细胞计数 ,并于缺血前及再灌注后 2h取肺组织行病理学检查及测其湿干重比、丙二醛含量。结果 :再灌注后Ⅱ、Ⅲ组和Ⅳ组右房血白细胞 /左房血白细胞比值显著低于Ⅰ组 (P <0 .0 5 ) ;与Ⅰ组比较 ,再灌注后Ⅱ、Ⅲ、Ⅳ组肺组织的湿干重比及丙二醛含量均明显降低 (P <0 .0 5 ) ,肺组织病理改变减轻。结论 :UTI能减轻肺缺血再灌注损伤     

腺苷A2a受体/Krüppel样因子5对缺血再灌注损伤大鼠心肌的影响

目的：探讨腺苷A2a受体/Krüppel样因子5(KLF5)对缺血再灌注损伤大鼠心肌的影响。方法：42只250～300 g雄性SD大鼠随机分为4组：假手术组（Sham组,n=6）、缺血再灌注组（I/R组,n=12）、缺血再灌注+腺苷A2a受体特异性激动剂CGS21680组（I/R+CGS组,n=12）、缺血再灌注+腺苷A2a受体拮抗剂ZM241385组（I/R+ZM组,n=12）。采用结扎左冠状动脉前降支再灌注的方法制备大鼠心肌缺血再灌注损伤模型。I/R+CGS组于再灌注前5 min静脉注射CGS21680后持续泵注60 min,CGS+ZM组于再灌注前5 min静脉注射ZM241385。于造模前,缺血5 min,再灌注10 min、45 min及120 min时分别记录各组大鼠的心率（HR）、平均动脉压（MAP）以及心率与收缩压乘积（RPP）。再灌注结束后取血液,酶联免疫吸附测定法检测血清心肌钙蛋白I(c TnI)和成纤维细胞生长因子21(FGF21)水平。再灌注结束后再次结扎左冠状动脉前降支,采用TTC染色法确定心肌梗死面积。处死大鼠,采用Western blot法检测缺血区心肌组...     

外源性促红细胞生成素对大鼠肺缺血再灌注组织AQP1表达的影响

目的探讨促红细胞生成素(EPO)对大鼠肺缺血再灌注组织水通道蛋白1(AQP 1)表达的影响。方法将60只健康Wistar大鼠随机分为假手术组、缺血再灌注组和EPO实验组,检测各组肺组织AQP 1蛋白和mRNA的表达,镜下观察肺组织病理,并检测肺水含量。结果 EPO实验组中AQP 1蛋白及mRNA的表达与缺血再灌注组、假手术组相比增高,肺水含量与缺血再灌注组相比降低,差异均有统计学意义。镜下病理提示EPO实验组肺组织水肿程度较缺血再灌注组减轻。结论外源性EPO能增加大鼠肺缺血再灌注组织AQP 1的表达,减轻缺血再灌注肺组织的水肿程度。     

盐酸纳美芬缺血后处理通过Sirt1/Nrf2/HO-1轴抑制铁死亡途径减轻大鼠肺缺血-再灌注损伤

目的研究纳美芬缺血后处理通过激活Sirt1/Nrf2/HO-1轴抑制铁死亡途径减轻肺缺血-再灌注损伤的作用及其机制。方法将60只大鼠随机均分为假手术组、模型组(I/R)、纳美芬组、纳美芬+EX527 组、纳美芬+ML385 组、纳美芬+Fe-柠檬酸盐组共6组, 每组10只。假手术组大鼠不行缺血再灌注处理, 未予药物治疗。I/R组大鼠采用阻断左肺门法建立肺缺血-再灌注模型, 未给予药物治疗。纳美芬组大鼠于肺循环再灌注前5 min予尾静脉注射纳美芬(15 μg/kg)。纳美芬+EX527 组、纳美芬+ML385组、纳美芬+Fe-柠檬酸盐组分别于造模前2 h腹腔注射EX527(5 mg/kg)、ML385(30 mg/kg)、Fe-柠檬酸盐(15 mg/kg), 同时在肺循环再灌注前5 min时尾静脉注射纳美芬(15 μg/kg)。各组大鼠于再灌注3 h末留取处死后留取左肺上叶组织, 检测肺组织湿/干重比值, 评估各组大鼠肺组织损伤程度, 检测肺组织Fe2+、MDA和TNF-α、IL-6含量、GSH活性以及Sirt1、Nrf2、HO-1、ACSL4、GPX4表达水平。结果与假手术组比较, 模...     

免疫因素在大鼠肺缺血再灌注损伤中的作用

目的探讨免疫因素在大鼠肺缺血再灌注(I/R)损伤中的作用。方法选取90只健康雄性Wistar大鼠,随机分为3组,即为I/R组(左肺I/R组),Sham组(假手术组),C组(对照组),均于缺血30 min、再灌注60、120 min时采集标本,检测肺组织的湿/干重比(W/D),支气管肺泡灌洗液的蛋白总量(TP),白细胞数目(WBC),中性粒细胞(PMN)的百分比及肺组织匀浆肿瘤坏死因子(TNF)-α、IL-1、IL-6及IL-8含量。结果在各组的对应时间点,I/R组中再灌注60、120 min时,W/D比值、WBC、PMN比例及TP含量明显高于C组及Sham组(P<0.05);I/R组中再灌注120 min,W/D比值、WBC、PMN比例及TP含量明显高于I/R组中再灌注60 min(P<0.05);I/R组中缺血30 min,肺组织匀浆TNF-α含量明显高于C组及Sham组(P<0.05);I/R组中再灌注60 min及再灌注120 min时,肺组织匀浆TNF-α、IL-1、IL-6及IL-8含量明显高于C组及Sham组(P<0.05);I/R组中再灌注120 min时,肺组织匀浆TNF-α、IL-1、IL-6及IL-8含量明显高于I/R组再灌注60 min时(P<0.05)。结论免疫因素在大鼠肺I/R损伤发挥重要作用。     

缺血后处理对高血脂大鼠缺血再灌注心肌Bcl-2及Bax蛋白表达的影响

目的 观察缺血后处理对高血脂大鼠缺血再灌注心肌Bcl-2及Bax蛋白表达的影响.方法 选择高血脂SD大鼠36只,随机分为3组:假手术组、缺血再灌注组、缺血后处理组,每组12只.制备大鼠心肌缺血再灌注模型.缺血再灌注组:收紧结扎线缺血40 min,放松结扎线再灌注240 min;缺血后处理组:缺血40 min后,再灌注10 s,缺血10 s,连续3个循环,然后再灌注240 min;假手术组:开胸后穿线做套环,但不收紧结扎线.再灌注结束后自右颈动脉采血测定血清肌酸激酶(CK)活性,用TUNEL法检测再灌注心肌凋亡程度,采用免疫组织化学方法检测Bcl-2及Bax蛋白的表达情况.结果 ①血清中CK活性的测定:再灌注结束后缺血后处理组和缺血再灌注组CK活性明显高于假手术组[分别为(789.68±67.34),(932.86±84.17),(252.48±19.78)U/L,P<0.05],缺血后处理组明显低于缺血再灌注组(P<0.05).②心肌凋亡细胞计数:再灌注结束后假手术组未见明显细胞凋亡(<5%),缺血后处理组心肌细胞凋亡率明显低于缺血再灌注组[分别为(11.9±2.7)%,(21.2±3.5)%,P<0.05].③与缺血再灌注组相比,缺血后处理组Bcl-2蛋白表达增加(P<0.05),Bax蛋白表达减低(P<0.05).结论 缺血后处理可以增加高血脂大鼠缺血再灌注心肌Bcl-2蛋白表达、降低Bax蛋白表达,进而抑制凋亡.     

红花注射液对肺缺血再灌注损伤时细胞凋亡及Bcl-2和Bax基因的影响

目的探讨细胞凋亡与肺缺血再灌注损伤的关系以及红花注射液的干预及机制。方法健康日本大耳白兔84只,随机分为对照组、缺血再灌注1、3、5h组和红花干预1、3、5h组。复制在体肺缺血再灌注损伤模型。采用电镜和原位缺口末端标记法观测肺组织细胞凋亡情况,并计算凋亡指数;免疫组织化学和原位杂交技术检测各组肺组织Bcl-2和Bax基因表达的变化。结果缺血再灌注组肺组织细胞凋亡指数和Bcl-2、Bax蛋白及mRNA均显著高于对照组(P<0.01)。红花干预组肺组织凋亡指数、Bax蛋白及Bax mRNA低于缺血再灌注组,而Bcl-2蛋白、Bcl-2mRNA以及Bcl-2与Bax的比值较缺血再灌注组上调(P<0.01或P<0.05)。电镜观察发现,缺血再灌注组肺毛细血管内皮细胞和Ⅱ型肺泡上皮细胞超微结构损伤明显,红花干预组损伤明显减轻。肺组织凋亡指数与Bax蛋白、Bax mRNA呈显著正相关(r分别=0.926,0.913;均P<0.01),与Bcl-2/Bax蛋白、Bcl-2/Bax mRNA的比值呈负相关(r分别=-0.367,-0.375;均P<0.01)。结论肺组织细胞凋亡参与了肺缺血再灌注损伤的发生,红花注射液可能通过下调Bax基因的表达,提高Bcl-2/Bax的比值抑制肺组织细胞凋亡,从而减轻肺缺血再灌注损伤。     

Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study

OBJECTIVE:

To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion.

METHODS:

Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR) and ischemia-reperfusion + tramadol (IR+T). The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively). All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v.) immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p.), the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies.

RESULTS:

Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both). Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group.

CONCLUSIONS:

On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion.     

The influence of iloprost on acute lung injury induced by hind limb ischemia-reperfusion in rats

The local ischemia-reperfusion (I/R) process gains a systemic nature and affects distal organs. The remote effects of I/R are most frequently observed in the lungs and pulmonary damage may vary from acute lung injury with mild dysfunction to severe respiratory failure or the acute respiratory distress syndrome. In this hind limb I/R induced experimental lung injury model two groups of rats as IR and ILO were determined. Both groups underwent 60 min of ischemia and 120 min of reperfusion. While ILO group received iloprost in saline, IR group received only saline before reperfusion period intravenously. Serum myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels and total antioxidant capacity (TAC) and lung tissue MPO activity, MDA levels and Na+-K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The MPO activities in serum and lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01). The MDA levels in lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01), but the decreases were not significant in serum MDA levels (P=0.052). Serum TAC and lung tissue Na+-K+ ATPase activity levels were found to be increased in ILO group compared to IR group (P < or = 0.01). Lung histology showed marked improvement by iloprost compared to the IR group in this study. Iloprost has been found to be effective in attenuating ischemia reperfusion-induced remote organ damage, in this case, lung injury, in rats.     

脂联素对大鼠心肌缺血-再灌注损伤时心律失常的影响

目的：观察脂联素对大鼠心肌缺血再灌注损伤时心律失常的影响并探讨其可能机制。方法：32只8周龄雄性大鼠被随机分为假手术组、缺血一再灌注（IR）组、地尔硫卓组和脂联素（APN）组,每组8只。①假手术组：只穿线,旷置90min;②IR组：先阻断血流30min,再灌注60min;③地尔硫卓组和APN组：先阻断血流30min,于再灌注开始时,从鼠尾静脉分别注射地尔硫卓（3．5μg／g·min）、APN（60ng／g·min）．再灌注60min。以Medlab生物信号采集处理系统连续监测各组心电图的变化。各模型组于再灌注60min后处死大鼠。测定血清、心肌组织一氧化氮（NO）的含量。结果：（1）与假手术组比较,IR组再灌注60min时段里．8只大鼠均出现再灌注心律失常．再灌注过程中ST段抬高的幅度显著增高（P〈0．001）,心肌组织、血清中NO含量均明显降低（P〈0．001）;（2）与IR组比较．APN组再灌注60min时段里,没有出现再灌注心律失常,再灌注过程中ST段抬高幅度显著下降（P〈0．001）,心肌组织、血清中NO含量均明显升高（P〈0．001）,且优于地尔硫卓组（P〈0．001）。结论：脂联素对缺血一再灌注损伤造成的心律失常有一定的保护作用．其机制可能与脂联素增加心肌组织、血清中NO含量有关。     

Intermedin预处理对大鼠肾脏缺血再灌注损伤修复过程中细胞周期蛋白表达的影响

目的 观察Intermedin(IMD)预处理对大鼠肾脏缺血再灌注损伤(IRI)修复过程中细胞周期蛋白(cyclin)D1、cyclin E以及其依赖性激酶(CDKs)表达的影响,从而探讨IMD在这一过程中促进肾组织再生修复的作用机制.方法 健康雄性Wistar大鼠共144只,体质量180～220 g,随机分为对照组、IRI组、转空质粒组、转IMD组,每组36只.IRI组切除右肾后钝性分离左侧腹主动脉及肾动脉;转空质粒组、转IMD组大鼠切除右肾后,在六氟化硫微泡(声诺维)介导下将空质粒及IMD质粒转染入左肾;1周后分别制作肾脏IRI模型.每组于再灌注第1、2、3、4、7、14天时各取6只留取肾组织标本.检测各组肾组织中cyclin D1与CDK4,cyclinE与CDK2的表达.统计学处理采用单因素方差分析和t检验.结果 IRI组cyclin D1、cyclin E以及CDK4、CDK2于再灌注后第1、2、3、4、7天表达逐渐增高,第7天时到达最高峰,第14天时仍有少量表达,与对照组比较差异有统计学意义(F值=54.92,69.69,61.28,77.38,P均＜0.05).转IMD组上述指标在第1天即开始显著增高,第2、3、4、7天呈进行性下降,至第14天时恢复正常,与IRI组相比差异具有统计学意义(F值=54.92,69.60,61.28,77.38,P均＜0.05);转空质粒组与IRI组以上指标差异无统计学意义.结论 IMD预处理在大鼠肾脏缺血再灌注损伤后早期能使cyclinD1、cyclinE以及CDK4、CDK2的表达明显上调,这一机制可能促进细胞周期进展从而加快肾组织再生修复.     

Toll样受体4在大鼠心肌缺血再灌注损伤中表达的实验研究

目的 观察心肌缺血再灌注早期Toll样受体4 mRNA(TLR4 mRNA)及蛋白表达,探讨TLR4在心肌缺血再灌注损伤中的作用.方法 雄性SD大鼠随机分为2组:假手术组(Sham组)、缺血再灌注组(IR组),每组36只,建立大鼠心肌缺血再灌注模型,按照不同的再灌注时间(0、0.5、1、24和8 h)处死动物.光镜和电镜观察心肌组织形态及超微结构改变.免疫组化检测心肌TLR4蛋白表达情况.实时定量逆转录聚合酶链反应定量心肌TLR4 mRNA表达水平.酶联免疫吸附试验测定心肌中肿瘤坏死因子-α(TNF-α)含量.结果 (1)Sham组心肌组织形态及超微结构改变不明显;IR组心肌损伤较重,缺血心肌恢复血液灌注8 h内,其病理学变化未见显著改善.(2)Sham组与IR组TLR4蛋白都有阳性表达,IR组TLR4表达增加,且以再灌注1 h最为明显(19.62±3.84,P＜0.01).(3)与Sham组比较,IR组心肌,TLR4 mRNA表达水平均出现不同程度上调,以再灌注1 h达到峰值[(4.03±0.85)×10-2,P＜0.01],而Sham组各时间点未见明显改变.(4)IR组心肌TNF-α水平高于各对应时间点Sham组(P均＜0.05),且心肌TLR4 mRNA表达与TNF-α呈正相关(r=0.728,P＜0.01).结论 心肌缺血再灌注早期,心肌TLR4表达迅速上调,TLR4的激活可能通过促进TNF-α等炎性因子的产生分泌增多来介导心肌缺血再灌注损伤.     

Effect of sevoflurane on tissue permeability of lung ischemia-reperfusion injury in rats

Objective:To investigate the effect of sevoflurane on tissue permeability of lung ischemiareperfusion injury(LIRI)in rats.Methods:A total of 45 wistar rats were randomly divided into3 groupsⅠ,Ⅱ,Ⅲ.Modified Eppinger method was adopted to establish the rat lung ischemiareperfusion injury model.GroupⅠserved as the control group,groupⅡas ischemia reperfusion group,groupⅢas sevoflurane ischemia-reperfusion group.Blood gas index,lung permeability index(LPI)change,lung tissue pathology change and lung water content were observed and compared between groups of rats at different time points.Results:During ischemia reperfusion,all rats kept balance of the MAP during different time points,SPO_2 of groupⅡandⅢdecreased significantly thanⅠgroup(P0.05);after reperfusion lung permeability index in GroupⅡandⅢwas higher than the control group significantly(P0.05),120 min after reperfusion LPI change and iujury of groupⅢwas significantly lower thanⅡgroup(P0.05);interstitial and alveolar cavity effusion in of groupⅢwere lower than that of groupⅡ.Conclusions:Sevoflurane pretreatment can reduce the lung tissue permeability,and LIRI plays a protective role in LIRI.     

缺血后处理对大鼠急性心肌缺血再灌注损伤的影响

目的观察在体条件下缺血后处理对大鼠心肌缺血再灌注损伤的作用及可能的途径。方法建立大鼠在体缺血再灌注模型,将30只大鼠随机分为假手术组、缺血再灌注组、缺血后处理组、缺血预适应组。于再灌注末测定心肌酶,超氧化物歧化酶(SOD)及丙二醛(MDA)的含量,并测定心肌组织梗死面积。结果与缺血再灌注组相比,缺血后处理组与缺血预适应组心肌梗死面积明显减小,血浆肌钙蛋白I及MDA的含量均降低(P<0.05),血浆SOD活性升高(P<0.05)。结论缺血后处理可减轻心肌缺血再灌注损伤,具有心肌保护效应。     

Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression

AIM: To detect the effect of acid fibroblast growth factor (aFGF) on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion (I-R) injury in order to explore the protective mechanisms of aFGF. METHODS: Male rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group (R), aFGF treatment group (A), intestinal ischemia group (I), and sham-operated control group (C). In group I, the animals were killed after 45 min of superior mesenteric artery (SMA) occlusion. In groups R and A, the rats sustained for 45 min of SMA occlusion and were treated with normal saline (0.15 mL) and aFGF (20 μg/kg, 0.15 mL), then sustained at various times for up to 48 h after reperfusion. In group C, SMA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique (TUNEL). Intestinal tissue samples were taken not only for RT-PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS: In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were (41.17±3.49)%, (42.83±5.23)%, and (53.33±6.92)% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points (50.67±6.95)%, (54.17±7.86)%, and (64.33±6.47)%, respectively, (P<0.05)). The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group (P<0.05) at 2-12 h after reperfusion, while the mRNA levels of P53 and P21WAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion (P<0.05). CONCLUSION: P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.     

An angiotensin II type 1 receptor blocker, candesartan, increases myocardial apoptosis in rats with acute ischemia-reperfusion.

Angiotensin II (Ang II) and apoptosis contribute significantly to myocardial ischemia-reperfusion (I-R) injury. Evidence indicates that Ang II may activate apoptosis in myocytes. The present study was undertaken to investigate the effects of angiotensin receptor blockers (ARBs), candesartan, on the apoptosis of cardiac myocytes in rats after I-R. Rats were divided into a control group, a candesartan group I (0.015 mg/kg), and a candesartan group II (0.03 mg/kg). Candesartan was intravenously administered 30 min before ischemia. All rats were subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The data showed that left ventricular (LV) systolic pressure and LV +dp/dt was decreased after administration of candesartan, but increased after reperfusion in the candesartan group II, compared with those in the candesartan group I and control group. LV -dp/dt was decreased after candesartan administration in candesartan group II. The number of apoptotic cells in the candesartan groups (497+/-204 and 543+/-254, respectively) was higher than that in the control group (287+/-166; p<0.05). There was no significant difference in infarct size among the three groups. However, plasma CPK was lower in the candesartan groups than in the control group. Northern blot analysis showed that p53 mRNA was upregulated in the candesartan groups, in association with increased expression of bax mRNA. Immunohistochemical analysis showed that p53 and bax immunoreactivity were increased in both of the candesartan groups. In conclusion, candesartan increased apoptosis in the rat hearts after acute I-R, and this increase was possibly mediated by upregulation of p53 and bax gene expressions. In addition, candesartan was shown to improve LV function, in association with reduction of CPK release.