二氧化硫预处理对心肌缺血再灌注损伤大鼠二氧化硫/天门冬氨酸氨基转移酶体系的影响

目的 探讨二氧化硫(SO2)预处理对心肌缺血再灌注损伤大鼠的保护作用及对心肌组织中SO2/天门冬氨酸氨基转移酶(AAT)体系的影响.方法　24只健康清洁级雄性Wistar大鼠随机分为假手术组、缺血再灌注组(I/R组)、SO2预处理组(I/R+S组).结扎大鼠左侧冠状动脉30 min,再灌注120 min,制备心肌缺血再灌注模型;I/R+S组大鼠在缺血前10 min用1 μmoL·kg-1SO2颈外静脉注射预处理.采用全自动生化检测仪检测大鼠血浆CK和LDH水平,用高效液相色谱法测定其心肌组织中SO2水平,采用蛋白免疫印迹法检测其心肌组织AAT1和AAT2蛋白表达水平.结果 缺血再灌注后,I/R组及IR+S组血浆CK、LDH水平均较假手术组明显增高(P＜0.01,0.05),I/R+S组血浆CK、LDH水平较I/R组均明显降低(Pa＜0.05).与假手术组比较,I/R组大鼠心肌组织匀浆中SO2水平显著降低(P＜0.05),I/R+S组无明显变化;I/R+S组SO2水平较I/R组显著增高(P＜0.01).I/R组大鼠心肌组织AAT1蛋白表达较假手术组显著降低(P＜0.01),I/R+S组与假手术组比较差异无统计学意义(P＞0.05),而I/R+S组AAT1蛋白表达则较I/R组显著增高(P＜0.01);AAT2蛋白表达在3组间的差异无统计学意义(P＞0.05).结论　SO2预处理可明显降低心肌缺血再灌注大鼠血浆中心肌酶活性,具有心肌保护作用,并对心肌组织中SO2/AAT体系具有上调作用.     

心肌缺血预适应家兔血浆内皮素及血清一氧化氮水平变化的意义

目的探讨心肌缺血预适应家兔血浆内皮素(ET)及血清一氧化氮(NO)水平的变化,探讨其在心肌缺血预适应过程中的作用。方法16只新西兰大耳白兔随机分为2组。缺血再灌注组(I/R组):结扎其冠状动脉左室支40min后再灌注120min;缺血预适应组(IP组):先予缺血预适应的过程,结扎冠状动脉左室支5min,放松冠脉血管后再灌注5min,反复操作3次,再按照I/R组进行操作。实验开始前取血测定血清CK、LDH、NO及血浆ET水平,2组动物均在结扎左室支40min、再灌注120min复测NO及ET水平,观察NO和ET变化。结果IP组阻断40min及再灌注120min血浆ET水平及LDH升高低于I/R组,二组比较差异有统计学意义(Pa<0.01),血清NO水平升高多于I/R组,二组比较差异有统计学意义(P<0.01)。IP组再灌注120min,CK水平升高于I/R组,心肌损伤程度小于I/R组。结论心肌缺血预适应家兔NO及ET水平发生明显变化,缺血预适应过程中NO水平升高增强了心肌对缺血的耐受性,ET水平降低减少了心肌缺血过程中其对心肌的损伤。     

钙敏感受体在大鼠心肌缺血/再灌注损伤中的作用

目的观察钙敏感受体在大鼠心肌缺血/再灌注损伤中的作用及其机制。方法30只Wistar大鼠随机分为3组(每组10只):假手术组(sham组)、缺血/再灌注组(I/R组)和钙敏感受体激动剂组(Gdcl3组),采用冠状动脉结扎和松结的方法,制备大鼠在体心肌缺血/再灌注损伤模型。分别测定血清一氧化氮(NO)、丙二醛(MDA)、超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)水平,光镜及透射电镜下观察心肌结构病理变化。结果I/R组血清LDH、MDA水平明显高于sham组(P<0.01),NO、SOD低于sham组(P<0..01);Gdcl3组血清LDH、MDA水平明显高于I/R组(P<0.01),而NO、SOD低于I/R组(P<0.01)。光镜及透射电镜下可观察到Gdcl3组心肌结构破坏,心肌细胞呈灶状或片状坏死;线粒体损伤,核皱缩,核染色质边集,其病理学改变程度较I/R组严重。结论钙敏感受体激活可使氧自由基产生增加,减少NO含量,降低SOD活性,加重心肌缺血/再灌注损伤。     

血栓通注射液对大鼠小肠缺血再灌注损伤的作用

目的采用肠系膜上动脉(SMA)缺血再灌注(I/R)模型,观察血栓通注射液对大鼠小肠I/R损伤的防治作用。方法将30只大鼠随机分为假手术组、I/R组、治疗组。治疗组于SMA再灌注前15分钟静脉注射血栓通注射液,I/R组按同样方式注射生理盐水,假手术组除不夹闭SMA外,其余操作同I/R组。分别观察平均动脉压(MABP)、血浆一氧化氮(NO)、小肠粘膜出血程度、肠组织湿/干重比值、丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性。结果与假手术组比较,I/R组再灌注后60分钟MABP、血浆NO含量显著下降,肠组织湿/干重比值、MDA浓度明显升高(P<0.01),而SOD活性无变化(P>0.05)。治疗组,则能明显减缓这种趋势,各项指标改善,小肠粘膜损伤程度明显减轻(P<0.01)。结论血栓通注射液对大鼠小肠I/R损伤有一定保护作用,其作用机制与抑制脂质过氧化和NO含量增加有关。     

山楂叶总黄酮对大鼠肾缺血/再灌注损伤的保护作用

目的探讨山楂叶总黄酮(TFHL)对大鼠肾缺血/再灌注(I/R)的作用。方法采用在体夹闭双侧肾动脉60min后恢复灌注的方法复制大鼠肾I/R损伤的模型,夹闭动脉前30min静脉注射TFHL30或60mg/kg。检测再灌注1、24h后血清BUN、血Scr及TNF-α和IL-1水平及再灌注24h后肾组织丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果TFHL能显著降低I/R导致的血清BUN和Scr升高,增加尿量,减少TNF-α和IL-1产生,提高肾组织SOD活性,减少MDA生成。结论TFHL能明显减轻肾I/R损伤,有效改善肾功能,其机制与TFHL减少脂质过氧化反应,减少细胞因子TNF-α和IL-1水平有关。     

氨力农对大鼠在体肺缺血再灌注损伤的保护作用

目的：探讨氨力农对在体肺缺血再灌注（I/R）损伤的保护作用。方法：夹闭大鼠左肺门1.5 h,再灌注2 h,建立在体缺血再灌注模型。将24只SD大鼠随机分成假手术组,缺血再灌注组（I/R组）和氨力农组（AMR组）,AMR组缺血前30 min给予颈静脉注射氨力农10 mg/kg,再灌注前5 min颈静脉注射氨力农10 mg/kg。再灌注2 h后采颈动脉血检测血气、白细胞介素-1β（IL-1β）、白细胞介素-8(IL-8)、肿瘤坏死因子-α（TNF-α）;摘取左肺测湿干比、超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量并行病理学检查。结果：再灌注2 h后,动脉血氧分压和二氧化碳分压3组间差异无显著性;I/R组肺湿干比和MDA（nmol/mg prot）含量分别为5.3±0.5和0.66±0.16,显著高于假手术组,AMR组上述指标降低至4.8±0.2和0.51±0.09;SOD（U/mg prot）在I/R组为39.3±3.0 ,AMR组为54.7±6.8,较I/R组升高;I/R组血清IL-1β（pg/mL）、IL-8 （pg/mL）、TNF-α(pg/mL)含量分别为22.08±3.85,21.92±5.56,30.50±3.77较假手术组显著升高, AMR组上述指标为16.66±3.02,14.73±2.75和 22.48±3.82,较I/R组低。病理学结果显示：三组动物肺组织结构基本正常,假手术组和AMR组无充血,I/R组充血明显且较其他两组炎症细胞明显增多。结论： 氨力农对肺缺血再灌注损伤具有保护作用,可能与其抗氧化和抑制炎症因子分泌有关。［中国当代儿科杂志,2007,9（3）：233-236］     

雌二醇对幼兔未成熟心肌缺血-再灌注损伤的保护作用

目的：探讨雌二醇对幼兔心肌缺血一再灌注损伤的保护作用。方法：采用离体心脏Langendorff灌注模型。根据停搏液的不同,将32只3～4周龄雌性日本大耳白兔随机分为4组(n =8) :①对照组 (C组 ) ,单用StThomasII停搏液 ;②雌二醇组(E2 组 ) ,StThomasII停搏液中加入10 -6mol/L 17 β雌二醇 ;③雌二醇受体阻断剂组 (B组) ,StThomasII停搏液中加入10 -6mol/L 17 β 雌二醇受体阻断剂4Hydroxy Tamoxifen ;④EB组 ,StThomasII停搏液中加入10 -6mol/L 17 β 雌二醇和 4 Hydroxy Tamoxifen。心脏停跳6 0min ,复灌后的不同时间点观察每组心功能各项指标的恢复率、心肌酶等生化指标及心肌超微结构的改变。结果：E2 组冠脉流出量的恢复率从复灌后6 0min起、左室发展压和左室压最大变化速率的恢复率从复灌后 4 0min起均高于其他 3组 (P <0 .0 1或 0 .0 5 ) ,心肌超微结构改变则较其他 3组轻 ,心肌含水量、MDA含量及冠脉流出液心肌酶含量均低于其他 3组(P <0 .0 5 ) ,E2 组心肌组织ATP含量高于C组和B组 (P <0 .0 5 )。结论：雌二醇对幼兔缺血一再灌注损伤心肌有较好的保护作用,其保护作用为心肌细胞雌二醇受体介导。     

雌二醇对幼兔未成熟心肌缺血-再灌注损伤的保护作用

目的　探讨雌二醇对幼兔心肌缺血一再灌注损伤的保护作用。方法　采用离体心脏Langendorff灌注模型。根据停搏液的不同 ,将 32只 3～ 4周龄雌性日本大耳白兔随机分为 4组 (n =8) :①对照组 (C组 ) ,单用StThomasII停搏液 ;②雌二醇组 (E2 组 ) ,StThomasII停搏液中加入 10 -6mol/L 17 β雌二醇 ;③雌二醇受体阻断剂组 (B组 ) ,StThomasII停搏液中加入 10 -6mol/L 17 β 雌二醇受体阻断剂 4 Hydroxy Tamoxifen ;④EB组 ,StThomasII停搏液中加入 10 -6mol/L 17 β 雌二醇和 4 Hydroxy Tamoxifen。心脏停跳 6 0min ,复灌后的不同时间点观察每组心功能各项指标的恢复率、心肌酶等生化指标及心肌超微结构的改变。结果　E2 组冠脉流出量的恢复率从复灌后 6 0min起、左室发展压和左室压最大变化速率的恢复率从复灌后 4 0min起均高于其他 3组 (P <0 .0 1或 0 .0 5 ) ,心肌超微结构改变则较其他 3组轻 ,心肌含水量、MDA含量及冠脉流出液心肌酶含量均低于其他 3组(P <0 .0 5 ) ,E2 组心肌组织ATP含量高于C组和B组 (P <0 .0 5 )。结论　雌二醇对幼兔缺血一再灌注损伤心肌有较好的保护作用 ,其保护作用为心肌细胞雌二醇受体介导。     

基质金属蛋白酶及其抑制物在容量过负荷致慢性心力衰竭大鼠血浆及心肌组织中的变化及意义

目的 观察容量过负荷致慢性心力衰竭大鼠血浆及心肌组织基质金属蛋白酶-8(MMP-8)及其抑制物-1(TIMP-1)的表达变化,探讨其在慢性心力衰竭发病中的病理生理作用.方法 雄性SD大鼠17只,随机分为分流组(n=9)和对照组(n=8).分流组通过腹主动脉下腔静脉穿刺术建立容量过负荷致慢性充血性心力衰竭动物模型,对照组大鼠除不做穿刺外,余操作过程同分流组.分别测定2组大鼠心功能及血流动力学指标,检测血浆MMP-8及TIMP-1水平,实时荧光定量PCR测定大鼠左心室、右心室MMP-8 mRNA、TIMP-1 mRNA的表达.结果 术后8周,分流组大鼠左心室收缩压、左心室舒张压、左心室内压差、左心室内压最大上升速率及最大下降速率较对照组明显降低(Pa＜0.05,0.01);左心室舒张末压较对照组明显升高(P＜0.05).分流组大鼠血浆MMP-8、TIMP-1水平均较对照组明显升高(Pa＜0.05).与对照组相比,分流组大鼠左心室心肌组织MMP-8 mRNA及左、右心室心肌组织TIMP-1 mRNA水平均有升高趋势,右心室MMP-8 mRNA水平有下降趋势,但2组比较差异均无统计学意义(Pa＞0.05);左心室和右心室心肌组织中MMP-8/TIMP-1明显降低,右心室较左心室下降更明显.结论 MMP-8与TIMP-1通过影响胶原代谢,参与容量过负荷致慢性充血性心力衰竭的病理生理过程.     

4-苯基乙酸对糖尿病大鼠胰岛β细胞凋亡的保护作用

目的 探讨4-苯基乙酸(4-PBA)对链脲佐菌素(STZ)诱导的1型糖尿病(T1DM)大鼠胰岛β细胞凋亡的保护作用.方法 STZ(60 mg/kg)一次性腹腔注射建立T1DM大鼠模型(n=22),并将成功制备的14只T1DM大鼠(血糖持续1周≥16.7 mmol/L)随机分为2组:T1DM组和4-PBA治疗组各7只.另外取对照组10只,腹腔注射等量柠檬酸-柠檬酸钠缓冲液.4-PBA治疗组大鼠自造模成功第10天开始以40 g/L 4-PBA[500 mg/(kg·d)]灌胃20 d,对照组和T1DM组大鼠予等量9 g/L盐水灌胃.观察各组大鼠体质量、血糖变化,处死后留取其血清和胰腺组织标本,测定血清胰岛素;光镜和脱氧核糖核苷酸末端转移酶介导的原位末端标记(TUNEL)法观察胰岛庀β细胞的形态学改变;反转录聚合酶链反应检测腺细胞基因Bax和Bcl-2 mRNA表达.结果 T1DM大鼠血糖在4-PBA治疗后渐下降,但仍未降到正常水平.T1DM大鼠血清胰岛素水平降低,4-PBA治疗后血清胰岛素水平有所增加.光镜和TUNEL显示T1DM大鼠4-PBA治疗后减少了由STZ引起的胰岛β细胞的凋亡(P<0.05).与对照组比较,T1DM组大鼠凋亡蛋白Bax mRNA显著上调(P<0.01),抗凋亡蛋白Bcl-2 mRNA显著下调(P<0.01).结论 4-PBA可减轻胰岛庀β细胞损害,使其不发生过敏度凋亡,从而降低血糖.     

The nitric oxide donor molsidomine prevents ischemia/reperfusion injury of the adult rat small intestine

It is suggested that gastrointestinal mucosal blood flow depends on a balanced release of vasoactive substances from the endothelium. The present study investigated the effects of molsidomine on the small intestine after ischemia-reperfusion (I/R) injury in four groups of 10 rats each composed: (1) SO, sham operation; (2) untreated I/R; (3) ML, I/R plus molsidomine pretreatment; (4) L-NAME, I/R plus N-omega-nitro-L-arginine methyl ester pretreatment. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileum specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histologic changes. Mean MDA levels in the SO, untreated I/R, ML, and L-NAME groups were 95.60 +/- 2.59, 136.90 +/- 4.35, 121.10 +/- 3.38, and 137.40 +/- 4.42 nmol/g wet tissue, respectively. Although the MDA level in the ML group was higher than in the SO group ( P < 0.0001), it was significantly lower compared to the untreated I/R and L-NAME groups ( P < 0.0001, P < 0.0001). Mucosal injury scores (MIS) in groups 1-4 were 0.2 +/- 0.42, 3.9 +/- 0.73, 1.5 +/- 0.70, and 4.1 +/- 0.56, respectively. In group 3 the MIS was significantly lower than in groups 2 and 4 ( P < 0.0001, P < 0.0001). Molsidomine plays a role in attenuating reperfusion injury of the small intestine by depression of tissue MDA levels and MIS and regulates post-ischemic intestinal perfusion while restoring the intestinal microcirculatory blood flow and histologic injury.     

二氧化硫对自发性高血压大鼠血管胶原重构的影响

目的 研究自发性高血压大鼠(spontaneously hypertensive rat,SHR)血管蕈构时二氧化硫(SO2)对Ⅰ、Ⅲ型胶原蛋白在主动脉管壁异常堆积的调节作用,进一步探讨SO2解SHR血管重构的作用机制.方法 4周龄雄性Wistar Kyoto(WKY)大鼠8只,同样周龄雄性SHR 16只随机分为SHR对照组(n=8)、SHR+Na2S03/NaHSO3(SO2供体)组(n=8).5周后测定大鼠血压,胸主动脉显微结构,血浆SO2含量以及主动脉Ⅰ、Ⅲ型胶原蛋白的表达.结果 (1)与WKY大鼠相比,SHR的血压升高53%,左室与全心重最比增加6%,血浆SO2含量下降44%(P＜0.01,P＜0.05);与SHR组相比,SHR+Na2SO3/NaHSO3组血压降低26%,血浆SO2含量升高28%(P均＜0.01).(2)各组大鼠胸主动脉壁厚与内径之比:SHR组较WKY大鼠增加28%(P＜0.01),SHR+Na2SO2/NaHSO3组较SHR组减少10%(P＜0.01).(3)各组大鼠胸主动脉中Ⅰ型胶原蛋白的表达:SHR较WKY大鼠增加10%(P＜0.01);SHR+Na2O3/NaHSO3组较SHR组减少5%(P＜0.01).(4)各组大鼠胸主动脉中Ⅲ型胶原蛋白的表达:SHR组较WKY组增加13%(P＜0.01);SHR+Na2SO3/NaHSO3组较SHR组减少8%(P＜0.01).结论 SO2能够抑制Ⅰ、Ⅲ型胶原蛋白在血管壁的表达,可能是其缓解高血压血管重构的作用机制之一.     

The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats

This study was designed to investigate the protective effect of trimetazidine [TMZ; 1-(2, 3, 4-trimethhoxibenzyl)-piperazine dihydrochloride], as an antioxidant agent, on torsion–detorsion-induced biochemical and histopathological changes in experimental testicular ischemia/reperfusion injury in rats. Twenty-seven male Wistar rats weighing 180–220 g were divided into five groups: control (C, n = 4), sham-operated (S, n = 4), ischemia (I, n = 6), ischemia–reperfusion (I/R, n = 6) and ischemia–reperfusion + trimetazidine (I/R + TMZ; n = 7). Control rats were used for basal normal values. In group I, 2 h torsion of the left testis was performed. In I/R and I/R + TMZ groups, following 2 h of torsion, 4 h detorsion of the testis was performed. In ischemia and I/R groups, physiologic saline was administered orally for 7 days, and the rats in I/R + TMZ group were pretreated orally with 5 mg/kg day TMZ for 7 days before inducing ischemia. At the end of each experiment, ipsilateral orchiectomies were performed for the tissue levels of malondialdehyde (MDA), glutathione peroxidase (GPx) enzyme activities and histopathological examinations in all groups. MDA levels were significantly reduced and GPx enzyme activities were significantly increased in testes in I/R+TMZ pretreated group compared to group I and I/R. The mean seminiferous tubular diameter (MSTD) and Johnsen’s score were significantly better in I/R+TMZ group than groups I and I/R. Pretreatment with TMZ decreased germ cell apoptosis and caspase-3 expression in the ischemic testis. The present results show that TMZ has a protective activity in the testicular injury caused by I/R, and provide the first evidence of the role of TMZ for the prevention of I/R-induced testicular injury.     

Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against intestinal ischemia and reperfusion injury in infant rats

Free radicals are important in development of intestinal ischemia-reperfusion (I/R) injury, leading to intestinal and pulmonary damage. We evaluated the effects of peroxynitrite decomposition catalyst FeTMPyP in infant intestinal I/R. Suckling rats underwent 40 min intestinal ischemia + 90 min reperfusion. At reperfusion, animals received saline or FeTMPyP. Groups were (n = 11 per group): 1) control+saline; 2) I/R+saline; 3) I/R+FeTMPyP. Increased histologic injury and ICAM-1 expression were observed in ileum of both I/R+saline and I/R+FeTMPyP rats, but P-selectin expression was increased in I/R+saline animals only versus controls. Myeloperoxidase (neutrophil infiltration marker) was increased in ileum and lungs of I/R+saline rats, but FeTMPyP prevented this in the ileum. I/R+saline animals showed higher malondialdehyde (lipid peroxidation marker) in ileum and lungs versus both control+saline and I/R+FeTMPyP rats. Glutathione was decreased in all I/R animals, but oxidized and total glutathione were higher in I/R+FeTMPyP than the I/R+saline group. Nitrate+nitrite concentration (systemic nitric oxide production) was elevated in I/R+saline but not in I/R+FeTMPyP animals. FeTMPyP provides limited protection against intestinal I/R in neonatal rats by reducing ileal P-selectin expression, systemic nitric oxide production, neutrophil infiltration in ileum and lipid peroxidation in both lungs and ileum; and preserving intestinal antioxidant capacity.     

Ⅰ型Bartter综合征患儿3例SLC12A1基因变异功能分析

目的:分析Ⅰ型Bartter综合征患儿SLC12A1基因变异的功能特性,探索分子伴侣类药物4-苯丁酸钠对SLC12A1基因变异体的纠正作用。方法:回顾性分析2017至2018年南京医科大学附属儿童医院收治的3例Ⅰ型Bartter综合征患儿的临床表现、生长发育情况、实验室检查结果及SLC12A1基因变异情况等,在人胚胎肾...     

二氧化硫对低氧性肺动脉高压大鼠肺动脉结构的影响

目的 探讨二氧化硫(sulfur dioxide,SO2)对于低氧性肺动脉高压大鼠肺动脉结构的影响.方法 将大鼠分为3组:对照组(n=8)、低氧组(n=8)和低氧+SO2组(n=10,给予Na2SO3/NaHSO3).对低氧组和低氧+SO2组大鼠进行低氧处理21 d.同时对照组置于常氧环境.检测各组大鼠肺动脉平均压.并通过光镜检测肌型小动脉相对中膜厚度(RMT),应用透射电镜观察各组大鼠肺小动脉超微结构的变化,检测血浆SO2含量.结果 低氧组大鼠肺动脉平均压[(5.12±0.51)kPa]较对照组[(2 25±0.50)Ida]高(t=5.091,P＜0.01),低氧组肺动脉RMT测定值(9.66±1.27)较对照组(6.83±1.57)高(t=3.392,P＜0.01),超微结构观察显示低氧组大鼠肺小动脉内皮细胞体积增大变性,内弹力层疏松厚薄不均.平滑肌细胞体积增大,细胞器丰富,细胞间见胶原原纤维增多,同时低氧组血浆SO2含量[(27.01±4.17)tunol/L]较对照组[(33.36±5.62)μmol/L]低(t=3.767,P＜0.05);低氧+SO2组大鼠的肺动脉平均压[(3.94±0.33)kPa]较低氧组[(5.12 ±0.51)kPa]低(t=2.712,P＜0.01),低氧+SO2组RMT测定值(6.97±1.83)较低氧组(9.66±1.27)低(t=3.009,P＜0.01),超微结构观察显示给予SO2干预后上述改变较低氧组明显改善,同时血浆SO2含量[(29.89±4.52)μml/L]较低氧组[(27.01±4.17)μmol/L]高(t=1.263,P＞0.05).结论 SO2对低氧性肺动脉高压大鼠肺小动脉结构具有重要的调节作用.     

Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver

Hepatic ischemia-reperfusion (I/R) injury may be developed in some conditions, such as trauma, major hepatic resection, hemorrhagic shock or liver transplantation. I/R injury of the liver causes hepatocellular damage that may lead to hepatic failure. A considerable body of evidence indicates that reactive oxygen species (ROS) and inflammation may contribute to hepatocellular injury in liver I/R. Leflunomide is an isoxazole derivative, and a unique immunomodulatory agent. In the present study, we examined the effects of leflunomide on the neutrophil activation with oxidative stress and some antioxidant enzymes in the reperfusion following I/R in the rat liver. Thirty-two rats divided into four groups: group 1 (control); was given leflunomide 10 mg/kg, i.g.; group 2 (SHAM), animals were only laparotomized; group 3 (liver I/R), and group 4 (liver I/R + Leflunomide). In group 4, rats were pretreated with leflunomide (10 mg/kg, i.g.) two doses prior to experiment. In groups 3 and 4, occluding the hepatic pedicel for 60 min induced ischemia and reperfusion was allowed thereafter for 60 min. At the end of the reperfusion period, rats were sacrificed. superoxide dismutase, catalase, nitric oxide, xanthine oxidase, malondialdehyde, protein carbonyl and myeloperoxidase levels were determined in hepatic tissue as well as histological examination with H and E staining. Group 3 animals demonstrated severe deterioration of liver morphology and a significant liver oxidative stress. Pretreatment of animals with leflunomide markedly attenuated morphological alterations and neutrophil activation, reduced elevated oxidative stress products levels and restored the depleted hepatic antioxidant enzyme. The findings imply that ROS play a causal role in I/R-induced hepatic injury, and leflunomide exerts hepatoprotective effects probably by the anti-inflammatory effect with radical scavenging and antioxidant activities.     

幼鼠慢性压力负荷性心力衰竭中心肌细胞凋亡的变化及卡维地洛的防治作用

目的　观察幼鼠心脏后负荷过高的慢性心力衰竭 (CHF)发展中心肌细胞凋亡变化及卡维地洛的防治作用。方法　采用腹主动脉缩窄术建立幼鼠CHF模型 ,术后 4周随机分 3组 :假手术对照组、CHF组、卡维地洛预防组。卡维地洛直接灌胃给药 ,8周后行血流动力学、心肌病理分析、心肌细胞凋亡及其相关基因Bcl 2、P53 蛋白表达水平。结果　与假手术组比较 ,CHF组左室收缩压 (LVSP)、左室舒张末压 (LVEDP)、左、右心室相对重量 (LVRW ,RVRW )、凋亡指数 (AI)、P53 基因蛋白表达水平显著升高 (P <0 .0 1) ,左室内压最大收缩率( +dp/dtmax)、左室内压最大舒张率 ( -dp/dtmax)、Bcl 2基因蛋白表达水平均显著降低 (P均 <0 .0 1)。与CHF组比较 ,卡维地洛组LVSP、LVEDP、LVRW、RVRW、AI、P53 基因蛋白表达水平下降 ,+dp/dtmax、-dp/dtmax、Bcl 2基因蛋白表达水平显著升高 (P <0 .0 1)。结论　心肌细胞凋亡在CHF发展过程中起重要作用。卡维地洛可降低心肌细胞凋亡发生及相关基因Bcl 2、P53 异常表达     

二氧化硫对低氧性肺动脉高压大鼠内源性硫化氢体系的调节作用

目的 研究二氧化硫( SO2)对低氧性肺动脉高压大鼠肺动脉内源性硫化氢(H2S)/胱硫醚-γ-裂解酶( CSE)以及H2S/巯基丙酮酸转硫酶(MPST)体系的调节作用.方法 将雄性Wistar大鼠(32只)随机分为对照组、低氧组、低氧+ SO2组和低氧+天冬氨酸异羟肟酸(hydroxamate,HDX)组,每组8只.低氧处理采用常压低氧的方法,氧浓度为10％,每天低氧6h,持续21 d.对照组大鼠在常氧环境中饲养.低氧处理结束后采用右心导管法测定肺动脉平均压,采用硫电极法测定肺组织H2S含量和H2S产率,采用免疫组化法检测各组大鼠肺小动脉内膜及中膜CSE和MPST的蛋白表达.结果 低氧组大鼠肺动脉平均压较对照组高[(33.38 ±6.32) mm Hg vs(16.74±3.81) mm Hg,1 mm Hg=0.133 kPa,P＜0.01];低氧+SO2组大鼠肺动脉平均压较低氧组低[(29.65±2.53)mm Hg vs(33.38±6.32) mm Hg,P＜0.01],低氧+HDX组大鼠肺动脉平均压较低氧组高[(39.44±6.26) mm Hg vs(33.38±6.32) mm Hg,P＜0.01].低氧组大鼠肺组织H2S含量[(2.02±0.43) μmol/g vs (3.11±0.42) μmol/g,P＜0.01]及H2S产率[(19.64±3.48) nmol/(g· min)vs(28.20±5.95) nmol/(g·min),P＜0.05]均较对照组低.给予SO2供体后,低氧+SO2组肺组织H2S含量[(2.73±0.20)μmol/g vs(2.02±0.43)μmol/g,P＜0.01]及H2S产率[(26.24±1.92) nmol/(g· min)vs(19.64±3.48) nmol/(g· min),P＜0.01]均较低氧组升高.当给予内源性SO2生成酶抑制剂HDX后,低氧+HDX组肺组织H2S含量[(1.64±0.23) μmol/g vs (2.02±0.43)μmol/g,P＜0.05]及肺组织H2S产率[(13.94±3.63) nmol/(g·min) vs (19.64±3.48) nmol/(g·min),P＜0.05]均较低氧组低.低氧组大鼠肺小动脉内膜[(0.31±0.02)vs(0.36±0.01),P＜0.01]及中膜[(0.27±0.01)vs (0.30±0.01),P＜0.01]中CSE蛋白表达均较对照组低.低氧+SO2组大鼠肺小动脉内膜CSE蛋白表达较低氧组高[(0.35±0.02) vs (0.31 ±0.02),P＜0.01].低氧+HDX组大鼠肺小动脉内膜CSE蛋白表达较低氧组低[(0.26±0.01) vs (0.31±0.02),P＜0.01].与对照组相比,低氧组大鼠肺小动脉内膜及中膜MPST的蛋白表达差异没有统计学意义.低氧+SO2组大鼠肺小动脉中膜MPST的蛋白表达较低氧组高[(0.32±0.02) vs (0.29±0.01),P＜0.01];而与低氧组相比,低氧+ HDX组大鼠肺小动脉内膜及中膜MPST的蛋白表达差异没有统计学意义.结论 外源性给予SO2供体可上调低氧性肺动脉高压大鼠肺小动脉内膜H2S生成酶CSE及肺小动脉中膜MPST蛋白表达,促进H2S生成增多,从而间接缓解低氧性肺动脉高压的形成.