The role of cell adhesion molecules in ischemic epididymal injury

Objective The aim of this study was to investigate the role of adhesion molecules in epididymal injury induced by ischemia-reperfusion (I-R) in the rats. Study design About 20 male Sprague-Dawley rats were separated into two groups. A sham operation was performed in group 1 (control). In group 2 (I-R), following 6 h of unilateral spermatic cord torsion, 1-h detorsion of the testis was performed. Then, epididymides were removed to measure the tissue levels of malondialdehyde (MDA) and to make histological examination. Results Malondialdehyde values increased in group 2. In group 2, the rats demonstrated significant disorganization of the epithelium and loss of microvilli in the epididymal tissue. No abnormal microscopic findings of the epididymis of the rats in the control group. The tenascin expression in the interstitial area of the epididymis was intense in group 2. Intercellular adhesion molecule-1 (ICAM-1) expression by intense brown staining was seen along the basement membrane in epididymal tissue from I-R group rats. The microvillus sites of the epithelia in I-R group were stained mildly by lectin. Conclusion The increased expression of adhesion molecules found in epididymal injury induced during of postischemic reperfusion may implicate importance of inflammatory infiltration.     

The effects of nitric oxide on the expression of cell adhesion molecules (ICAM-1, UEA-1, and tenascin) in rats with unilateral testicular torsion

Background/Purpose:

The aim of this study was to determine the effects of nitric oxide (NO) on the expression of adhesion molecules in the early course of testicular I-R injury in rats.

Methods:

Forty male Sprague-Dawley rats were separated into 4 groups, each containing 10 rats. A sham operation was performed in group 1 (control). In group 2 (I-R), after 6 hours of unilateral testicular torsion, 1-hour detorsion of the testis was performed. In group 3 (I-R/l-NAME), after performing the same surgical procedures as in group II, l-NAME was given for 30 minutes. In group 4 (I-R/Mol), after performing the same surgical procedure (torsion and detorsion) as in group II, molsidomine, an NO donor, was infused for 30 minutes. Then, ipsilateral orchiectomies were performed to measure the tissue levels of malondialdehyde (MDA) and NO and to make histologic examination.

Results:

MDA values and the testicular injury score decreased and NO values increased in the I-R/Mol-treated group compared with other experimental groups. The tenascin expression in the interstitial space and basement membrane of the tubuli seminiferi were milder in the I-R/Mol group compared with that of the I-R and the I-R/l-NAME. The acrosomes of the spermatids in I-R and I-R/l-NAME groups were stained mildly by lectin. In the I-R and I-R/l-NAME groups, the interstitial spaces, basement membrane of the tubuli seminiferi, and sertoli and germinal cells in testicular tissue were stained intensely by ICAM-1.

Conclusions:

The expression of adhesion molecules such as tenascin, lectin, and ICAM-1 in the torted testicular tissue may be a pathophysiologic sign of inflammation. NO regulates adhesion molecules expression.     

Chronic stress affects tyrosine phosphorylated protein expression and secretion of male rat epididymis

Chronic stress (CS) is shown to decrease the semen quality with changed expression of tyrosine phosphorylated (TyrPho) proteins in testicular and seminal tissues. However, the alterations of such proteins and fluid contents in the epididymis, producing sperm maturation factors, have never been reported. Sixteen adult rats were randomly divided into 2 groups (n = 8). The control animals were not subjected to stressors whereas CS rats were immobilised within restraint cage (4 hr/day) before cold forced-water swimming (15 min/day) for 60 days. Corticosterone, testosterone, blood glucose level (BGL), malondialdehyde (MDA) and biochemical components in epididymal fluid were assayed. Expressions of heat shock protein 70 (HSP-70), androgen receptor (AR) and TyrPho protein were investigated in epididymal tissue and fluid. Significantly, CS increased the corticosterone and BGL but decreased testosterone and epididymal substance levels. MDA level in tail epididymal fluid and HSP-70 expression in both regions of epididymal tissues and fluids, except in head epididymal fluid of CS were increased. Epididymal tissues showed the decrease of AR expression. Presence and changes of many TyrPho proteins were observed in CS. In conclusion, CS could affect functional proteins particularly TyrPho in epididymis, resulted in low semen quality.     

Protective effects of pretreatment with Radix Paeoniae Rubra on acute lung injury induced by intestinal ischemia/reperfusion in rats

Objective： To investigate the effect of pretreatment with Radix Paeoniae Rubra （RPR） on acute lung injury induced by intestinal ischemia/reperfusion in rats and its protective mechanism.
Methods： Thirty-two Wistar rats were randomly divided into four groups： Sham-operation group, ischemla/ reperfusion group （I/R group ）, RPR-pretreatment group and hemin group. The model of intestinal ischemia/ reperfusion was established by clamping the superior mesenteric artery for 1 hour followed by 2-hour reperfusion. The effect of RPR on the expression of heme oxygenase-1 （HO-1） in lung tissues was detected by immunohistochemistry and morphometry computer image analysis. Arterial blood gas analysis, lung permeability index, malondialdehyde （MDA） and superoxide dismutase （SOD） contents in lungs were measured. The histological changes of lung tissue were observed under light microscope.
Resalts： The expression of HO-1 in RPR-pretreatment group and hemin group was obviously higher than that in sham-operation group and I/R group （ P 〈 0.01 ）. The level of MDA and lung permeability index in RPR-pretreatment and hemin group were significantly lower than those in I/R group （P〈0.01 or P〈0.05）, while the activity of SOD in RPR-pretreatment and hemin group was obviously higher than that in I/R group （P〈0.01）. Under light microscope, the pathologic changes induced by I/R were significantly attenuated by RPR.
Conclusion： Intestinal ischemia/reperfusion may result in acute lung injury and pretreatment with RPR injection can attenuate the injury. The protective effect of RPR on the acute lung injury is related to its property of inducing HO-1 expression and inhibiting lipid peroxidation.     

The effect of duration of compression on lipid peroxidation after experimental spinal cord injury

The present study was performed to evaluate the effect of duration of acute spinal cord compression on tissue lipid peroxidation in rats. A clip compression method (1) was used to produce acute spinal cord injury. Rats were divided into 3 groups, each consisting of 10. At 1 hour after trauma all rats were sacrificed, and MDA content of the injured spinal cord segment was measured. The tissue MDA contents were 3.922 μmolMDA/gww in group 1 (control), 10.192 μmol MDA/gww in group 2 (30 seconds compression), and 12.147 μmolMDA/gww in group 3 (60 seconds compression). These results demonstrate that the length of duration of compression significantly enhances lipid peroxidation. Our study supported the view that persisting compression may cause progression of secondary mechanisms which may irreversibly eliminate any potential for recovery.     

An angiotensin II type-I receptor blocker,olmesartan medoxomil,attenuates lipid peroxidation in renal injury induced by subtotal nephrectomy

Background Lipid-related oxidative stress, such as that caused by malondialdehyde (MDA), acrolein, and 4-hydroxynonenal (4-HNE), is involved in vascular injury in diabetes and hypertension. Olmesartan medoxomil, a blocker of angiotensin II type-I receptor, is an antihypertensive drug with antioxidant properties. In this study, we examined the involvement of oxidative lipids and the effect of olmesartan on lipid peroxidation in the progressive renal injury induced by renal mass reduction in rats. Methods Rats were treated with vehicle or olmesartan (0.5 mg/kg or 10 mg/kg) for up to 8 weeks after subtotal nephrectomy. The expression of oxidative lipids and the effect of olmesartan on lipid peroxidation were evaluated by Western blotting and immunostaining of renal tissue. Results Immunohistochemical examination revealed that MDA, acrolein, and 4-HNE were scarcely detected in renal cortex in sham-operated rats. On the contrary, these oxidative lipids were observed in injured glomeruli and dilated renal tubules in the ablated kidneys. Western blotting of renal cortical tissue revealed that MDA- or acrolein-bound proteins were mainly detected in the range of 30–90 kDa. Treatment with olmesartan attenuated lipid peroxidation and glomerulosclerosis. The renoprotective and antioxidative effect was higher in rats that received a high dose of olmesartan than in rats in the low-dose group. Conclusions These results indicate that oxidative lipids reflect the progression of renal injury induced by subtotal nephrectomy in rats. Olmesartan may have a renoprotective effect, with attenuation of lipid peroxidation.     

Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion

Ohiective: To observe the role and mechanism of Coreleasing molecule (CORM)-2 in lung injury induced by ischemia-reperfusion (IR) of hind limbs in rats.Methods: A rat model of lung injury induced by IR of hind limbs was established.A total of 40 Sprague Dawley (SD) rats were randomly divided into 5 groups (n=8):sham,shanl+CORM-2,IR,IR+CORM-2and IR+dimethyl sulfoxide (DMSO).Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours,rats in the sham group underwent sham surgery without infrarenal aorta occlusion.rats in the IR+CORM-2 group and in the sham+CORM-2 group were given CORM-2 (10 pmol/kg in travenous bolus) 5 minutes before reperfusion or at the corresponding time points.while rats in the IR+DMSO group was treated with the same dose of vehicle (DMSO) at the same time.The lung tissue structure,polymorphonuclear neutrophil (PMN) count,wet-to-dry weight ratio (W/D),malondialdehyde (MDA) content,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression,I κ Bo degradation and nuclear factor (NF)-κB activity in the lungs were assessed.Results: As compared with the sham group.lung PMNs number,W/D,MDA content,MPO activity,ICAM-1 expression and NF-κB activity significantly increased in the IR group,but the level of I κ Bo decresed (P＜0.01).Compared with the IR group,lung PMNs number,W/D,MDA content.MPO activity and ICAM-1 expression significantly decreased in the IR+COMR-2 group (P＜0.01),while the level of I κ Ba increased.Conclusions: These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression.NF-κ B pathway and the leukocytes sequestration in the lungs following limb IR in rats,suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.     

The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study

Abstract Objective: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock. Methods: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40–50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups. Results: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05). Conclusion: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury.     

缺血后处理对骨骼肌缺血再灌注后肺损伤保护作用的机制

目的：探讨缺血后处理（I-postC）对大鼠双侧后肢骨骼肌缺血再灌注（I/R）后肺损伤的保护作用及机制。方法：阻断肾下腹主动脉建立大鼠双侧后肢骨骼肌I/R损伤模型。48只大鼠随机分为3组：I/R组、缺血预处理（IPC）组及I-postC组,每组16只。分别于再灌注后12、24h各处死8只,取肺组织标本,观察肺组织形态学、湿/干重比、丙二醛（MDA）及髓过氧化物酶（MPO）的变化。原位杂交和RT-PCR方法检测肺组织中细胞间黏附分子（ICAM）-1mRNA的表达,Western blot检测ICAM-1蛋白表达。结果：再灌注12或24h后I/R组有明显的弥散功能障碍,表现为间质浸润细胞增多并伴有明显水肿。IPC组和I-postC组的各项指标均较I/R组明显降低,差异有统计学意义（P〈0.01）,但2组之间差异无统计学意义（P〉0.05）。结论：I-postC可以减轻大鼠双侧后肢骨骼肌I/R后肺损伤,与IPC可能存在共同的作用机制。     

Effect of lindane on antioxidant enzymes in epididymis and epididymal sperm of adult rats

Aim: To find out the changes induced by lindane on the antioxidant enzymes in epididymis and epididymal sperm of adult rats. Methods: Adult male rats were orally administered lindane at a dose of 5.0 mg/kg body weight per day for 30 days. At the end of the treatment, the rats were sacrificed. The epididymis was removed and weighed and sperm were collected for sperm count, motility and biochemical studies. A 1% homogenate of epididymis was prepared and used for biochemical estimations. Results: In lindane-treated rats, there were significant reductions in the epididymal weight, epididymal sperm count and motility compared with the controls. Significant decreases in the superoxide dismutase (SOD), catalase, glutathione reductase and glutathione peroxidase activities and significant increases in the H2O2 generation and lipid peroxidation were also observed in the epididymis and epididymal sperm of lindane-treated rats. Conclusion: Lindane decreases the levels of antioxidant enzymes in the epididymis and epididymal sperm of adult rats thereby inducing oxidative stress.     

异丙苯过氧化氢体内致大鼠睾丸和附睾过氧化的初步研究

目的:建立异丙苯过氧化氢(cHP)体内过氧化模型,探讨cHP体内过氧化对大鼠睾丸组织和附睾精子的影响,及对精子核DNA断裂的影响。方法:90日龄雄性W istar大鼠52只,设cHP 1/10 LD50、1/6 LD50、1/4 LD503个剂量组和对照组,cHP 1/10 LD50、1/6 LD50组和对照组每组大鼠12只,1/4 LD50组大鼠16只。用无菌生理盐水稀释70%cHP水剂配制,按2 m l/kg经腹腔每日1次注射,对照组给同体积生理盐水,观察一般中毒症状和体征。连续1周,最后1次给药24 h后处死动物。分光光度法测定睾丸组织匀浆、附睾头部和尾部精子丙二醛含量,用单细胞凝胶电泳检测睾丸生精上皮细胞、附睾头部和尾部精子核DNA断裂发生率,计数附睾尾部精子活动率,睾丸和附睾常规石蜡切片,苏木精-伊红染色观察病理变化。结果:给予cHP大鼠活动稍差,无死亡,1/6 LD50、1/4 LD50 cHP组体重降低明显(P<0.001)。1/6 LD50、1/4 LD50 cHP组大鼠睾丸和附睾精子丙二醛浓度均明显高于对照组,附睾尾部精子活动率均明显降低,睾丸生精上皮细胞和附睾头部精子核DNA断裂发生率明显高于对照组,附睾尾部精子核DNA断裂的发生率与对照组差异无显著性(P>0.05)。1/10 LD50 cHP组大鼠体重变化、睾丸丙二醛浓度、附睾尾部精子活动率、睾丸生精上皮细胞和附睾精子核DNA断裂与对照组比较,差异均无显著性(P>0.05)。结论:1/6 LD50、1/4 LD50 cHP能在体内使大鼠睾丸和附睾精子发生过氧化,并使细胞核DNA发生断裂,核DNA断裂的主要部位可能在睾丸组织,对附睾尾部精子核DNA断裂无明显影响。     

【原创论文】同侧和对侧大鼠睾丸缺血再灌注损伤的生化效应和褪黑激素对此的保护作用

睾丸扭转（TT）,是一个多发于青春期男性的泌尿急症,如果不及时治疗,可致不孕不育。睾丸扭转所致缺血再灌注（I／R）损伤在睾丸损伤的病理生理过程中起一定作用。我们研究了褪黑激素在单侧睾丸扭转大鼠中同侧和对侧睾丸的氧化损伤效应：将21只青春期雄性Wistar大鼠分成三组,每组七只,处理如下：第1组（假手术组）：行左睾丸和双边睾丸假切除术;第2组（I/R组）：通过以下方式诱发缺血再灌注损伤（顺时针720°旋转左侧睾丸2小时,2小时后复位）：第3组（I／R＋MEL组）：大鼠经诱导缺血再灌注损伤和一次性褪黑激素注射（50mgkg-1,i．p）。处理后离体分离各组大鼠双侧睾丸,用于检测睾丸组织中抗氧化过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性,丙二醛、蛋白质羰基和一氧化氮的组织水平。较对照组,褪黑激素注射组同侧睾丸的脂质过氧化水平,相关酶活性降低,具有显著性（P〈0．05）,而在对侧的睾丸中相关酶活性变化无统计学意义（P〉0．05）。在对侧睾丸中,丙二醛水平改变具有明显统计学意义（P=0．009）。应用褪黑素能减轻老鼠同侧睾丸扭转所致缺血再灌注损伤的不利影响,而对于对侧睾丸,睾丸扭转影响不大。     

Contributions of heme oxygenase-1 in postconditioning-protected ischemia-reperfusion injury in rat liver transplantation

Background

Heme oxygenase-1 (HO-1), an oxidative stress-response gene up-regulated by various physiological and exogenous stimuli, has cytoprotective activities. Ischemic postconditioning (Postcon) can protect an organ from ischemia-reperfusion (I/R) injury. In the present study, we investigated the potential contributions of HO-1 to Postcon-dependent protection against I/R injury in rat liver transplantation models.

Materials and methods

Adult male Sprague-Dawley rats were randomly divided into four groups: sham group with laparotomy for liver exposure; I/R group with 24-hour cold ischemia of the donor liver; Postcon group with the same treatment as the I/R group plus ischemic Postcon; and zinc protoporphyrin (ZnPP HO-1 inhibitor) + Postcon group treated the same as the Postcon cohort with donors pretreated using ZnPP 24 hours before the I/R injury. We measured liver tissue and peripheral blood samples collected at 6 hours after reperfusion and serum transaminase levels, histopathology, liver tissue malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and HO-1 expression in the liver.

Results

Postcon significantly diminished the elevation of serum transaminases levels after I/R injury when compared with I/R and ZnPP+Postcon groups. Postcon treated rats showed significantly lower MDA production and higher SOD activity. HO-1 was induced in rat livers exposed to Postcon; its levels were obviously overexpressed after 6 hours in Postcon rats. Inhibiting the expression of HO-1, negated the protective effects of Postcon.

Conclusions

Induction of HO-1 in the Postcon condition played a protective role against hepatic I/R injury and enhanced the early antioxidative activity. The protective effects of Postcon were significantly associated with greater intrahepatic HO-1 expression.     

Tyrosine phosphorylation of insulin receptor substrates during ischemia/reperfusion-induced apoptosis in rat liver

Background  Phosphoregulation of signal transduction pathways is a complex series of reactions that may modulate the cellular response to ischemia–reperfusion (I–R). The aim of this study was to evaluate the effect of normothermic liver I/R-induced apoptosis on phosphorylation and activation of signal proteins in tyrosine kinase pathways. Materials and methods  In rats, a segmental normothermic ischemia of the liver was induced for 120 min. Liver apoptosis was determined using terminal deoxynucleotide-transferase-mediated deoxyuridine triphosphate nick end labeling assay, and activity of caspases-3 and -7 was determined by fluorescence. Liver tyrosine phosphorylation of proteins was examined by Western blot analysis. Results  Normothermic I–R resulted in increased in vivo caspases-3 and -7 activity and in liver apoptosis. Shc tyrosine phosphorylation and activation of ERK1/2 were increased after reperfusion, while tyrosine phosphorylation of IRS-1 and activation of PKB/Akt were decreased. Conclusions  Normothermic liver I–R leads to increased apoptosis and to modifications in protein tyrosine phosphorylation pathways. Scientific meetings: Presented to the World Transplant Congress, Boston, USA, July 22–27, 2006, the 7th World Congress of the International Hepato-Pancreato-Biliary Association, Edinburg, UK, September 3–7, 2006, and the 31st Congress of the Società Italiana Trapianti d’Organo, Modena, Italy, November 28–38, 2007. Raffaele Cursio and Claudia Miele have contributed equally to this work     

普罗布考防治大鼠顺铂急性肾损伤的实验研究

目的：复制大鼠顺铂急性肾损伤模型,研究氧化应激与核转录因子Sp1及凋亡的关系;探讨普罗布考对顺铂急性肾损伤的保护作用及作用机制。方法：24只SD雄性大鼠被随机分为生理盐水对照组、顺铂模型组、普罗布考干预组、普罗布考对照组,每组6只;检测尿N-乙酰-β-D-氨基葡萄糖甘酶（NAG）、血清肌酐（Scr）、血尿素氮（BUN）、肾组织匀浆液丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）,光镜观察肾脏病理改变;采用免疫组化染色检测肾组织Sp1蛋白表达;采用TUNEL染色检测肾小管上皮细胞凋亡。结果：与生理盐水对照组和普罗布考对照组相比,顺铂模型组大鼠血清BUN和Scr,尿NAG酶,肾脏组织匀浆MDA含量显著升高,肾组织匀浆GSH-Px活力显著下降（P〈0.01）;肾脏指数、肾小管损伤分数和肾小管上皮细胞凋亡百分比均明显增加（P〈0.01）;肾组织Sp1蛋白的表达上调。采用普罗布考干预后血清BUN和Scr,尿NAG酶,肾脏组织匀浆MDA含量显著下降（P〈0.05）;肾组织匀浆GSH-Px活力显著升高;肾脏指数、肾小管损伤分数和肾小管上皮细胞凋亡百分比均明显降低（P〈0.01）;肾组织Sp1蛋白的表达下调。结论：氧化应激和核转录因子Sp1在顺铂所致大鼠肾毒性中起一定作用;普罗布考对顺铂所致大鼠肾毒性有保护作用,其机制可能与抗氧化、抑制肾小管上皮细胞凋亡、下调肾组织Sp1蛋白表达有关。     

雌激素对大鼠肝切除肝缺血再灌注损伤中核因子-κB/IκB传导通路的影响及保护作用

目的 观察雌激素对大鼠肝切除肝缺血再灌注损伤中核因子-κB(NF-κB)/抑制蛋白(IκB)传导通路影响.方法 制作肝切除肝缺血再灌注损伤动物模型,雄性SD大鼠随机分为3组:假手术组(Sham组);肝切除肝缺血再灌注组(I/R组);肝切除肝缺血再灌注+雌激素组(I/R+ E2 组).分别在缺血再灌注后1、3、6h光镜下观察肝组织病理学改变,检测血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的水平和肝组织丙二醛(MDA)的含量及超氧化物岐化酶(SOD)的活性,免疫组织化学法测定肝组织NF-κB的表达,Western blot检测NF-κB抑制蛋白(IκB-α)和细胞间黏附分子-1(ICAM-1)表达,流式细胞仪检测细胞凋亡率.结果 再灌注后I/R组在各时相血清ALT、AST均显著高于I/R +E2组,并于6h达到峰值(P＜0.05).与I/R+E2组和Sham比较,I/R组肝细胞凋亡率显著升高(P＜0.01);肝组织中IκB-α表达降低,而NF-κB表达增高(P＜0.05);ICAM-1 和MDA的结果变化和NF-κB表达水平变化类似,SOD呈相反变化.在光镜下观察,I/R组肝小叶结构紊乱,肝窦淤血,肝细胞水肿变性,肝细胞片状坏死,在Sham组和I/R +E2组上述病理学变化明显改善.结论 雌激素对肝切除肝脏缺血再灌注损伤有显著保护作用,其作用机制可能与雌激素影响NF-κB/IκB传导通路、减轻脂质过氧化反应、减少炎症介质释放及抑制细胞凋亡有关.     

Mycophenolate mofetil attenuates liver ischemia/reperfusion injury in rats

Mycophenolate mofetil (MMF) has been gradually introduced into clinical liver transplantation in recent years. However, the effects of MMF on hepatic ischemia/reperfusion (I/R) injury and the potential mechanisms involved are not totally understood. We aimed to evaluate whether MMF could attenuate hepatic I/R injury. MMF (20 mg/kg) or vehicle was administered to Wistar rats by gavage. The rats were then subjected to hepatic ischemia. Liver cell apoptosis and the levels of aspartate aminotransferase, myeloperoxidase (MPO), xanthine oxidase (XOD) and malondialdehyde (MDA) were determined. Expression of vascular cell adhesion molecule-1 (VCAM-1) and activation of mitogen-activated protein kinases (MAPKs) were also investigated. Furthermore, the hepatic microcirculation was observed by intravital fluorescence microscopy. Rats pretreated with MMF exhibited significant alleviation of their postischemic liver function. Liver cell apoptosis and the tissue MPO, XOD and MDA levels were decreased by MMF pretreatment. MMF also improved I/R-induced hemodynamic turbulence, as evidenced by reduced hepatic perfusion failure and decreased numbers of rolling and adherent leukocytes. I/R injury induced activation of the MAPKs pathway while expression of VCAM-1 was downregulated by MMF pretreatment. In summary, MMF attenuates hepatic I/R injury through suppression of the production of reactive oxygen species and amelioration of postischemic microcirculatory disturbances.     

α-Lipoic acid and ebselen prevent ischemia/reperfusion injury in the rat intestine

Purpose  Reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study to evaluate the protective effect of α-lipoic acid (α-LA) and ebselen against intestinal I/R injury. Methods  Forty Sprague-Dawley rats were divided into five groups: a sham-operated group; an I/R group, subjected to intestinal ischemia for 45 min and reperfusion for 3 days; an I/R+α-LA group; an I/R+ebselen group; and an I/R+α-LA+ebselen group. We collected ileal specimens, to measure the tissue levels of malondialdehyde (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and to evaluate the histologic changes. Results  There was a significant decrease in SOD and GPx levels, with an increase in MDA and PCC levels and intestinal mucosal injury in the intestinal I/R group (P < 0.05). Superoxide dismutase and GPx levels were significantly higher, MDA and PCC levels were significantly lower, and intestinal injury was significantly less severe in the I/R+α-LA+ebselen group than in the I/R group (P < 0.05). Although shortened villi and epithelial lifting were seen in the I/R group, only slight mucosal injury was seen in the treatment groups. Conclusion  α-Lipoic acid and ebselen played an important role in attenuating I/R injury of the intestine by scavenging ROS and RNS.     

Effect of bisphenol A and co-administration of bisphenol A and vitamin C on epididymis of adult rats： A histological and biochemical study

Aim: To study the effect of bisphenol A on the epididymis and epididymal sperm of rats and the possible amelioration action of co-administration with vitamin C. Methods: Male Wistar rats were orally administered bisphenol A (0.2 μg·kg-1·day-1, 2 μg·kg-1·day-1 and 20 μg·kg-1·day-1) and 0.2 μg, 2μg and 20 μg bisphenol A + 40 mg vitamin C·kg-1·day-1 for 60 days. On day 61, rats were killed with anesthetic ether and sperm collected from epididymis were used for assessment of sperm count, motility and viability and biochemical studies. A 1 % homogenate of epididymis was prepared and used for biochemical estimations. Caput, corpus and cauda epididymis were fixed in Bouin's fixative for histological studies. Results: Administration of bisphenol A caused a reduction in the epididymal sperm motility and count and the sperm viability remained unchanged. The activities of superoxide dismutase and glu-tathione peroxidase decreased, while the levels of lipid peroxidation increased in epididymal sperm an