黄芪注射液对阿霉素性心肌细胞凋亡、内质网应激与缝隙连接蛋白表达的影响

目的：研究黄芪注射液对阿霉素（ADR）所致心肌病大鼠心肌细胞凋亡、内质网应激与缝隙连接蛋白表达的影响。方法：36只Wistar雄性大鼠随机分为3组（n=12）：对照组、ADR组及黄芪注射液组。对照组腹腔注射0.9% Nacl （10 ml/kg体重）;ADR组腹腔注射ADR 2 mg/kg体重;黄芪注射液组在每次腹腔注射ADR 2 mg/kg体重的同时,注射黄芪注射液10 g/kg体重,每周注射1次,共注射3次。实验第7周末,3组大鼠行心脏彩超检测左室舒张末期内径、左室收缩末期内径及左室射血分数;处死大鼠后取左心室组织行HE、Masson、醋酸铀及柠檬酸铅染色,于光镜及透射电镜下观察心肌病理及超微结构改变;采用TUNEL法检测大鼠心肌细胞凋亡,用免疫组化技术检测大鼠心肌细胞缝隙连接蛋白Cx43及p-Cx43表达,采用real time PCR检测大鼠心肌细胞内质网应激伴侣蛋白Grp78,ATF-4及CHOP表达。结果：与对照组比较,ADR组大鼠LVEDD、LVESD增大,LVEF减少;心肌纤维排列紊乱,心肌纤维间质水肿,大量淋巴细胞浸润;线粒体肿胀、破坏,呈空泡样;心肌细胞凋亡数明显增多（P<0.01）;内质网应激相关蛋白Grp78、ATF-4及CHOP表达明显增高（P<0.01）;缝隙连接蛋白Cx43表达减少,而p-Cx43表达增多。与ADR组比较,黄芪注射液组大鼠LVEDD、LVESD减少,LVEF增加;心肌病理及超微结构明显改善,同时心肌细胞凋亡数明显减少（P<0.01）;内质网应激伴侣蛋白Grp78、ATF-4及CHOP表达明显减少（P<0.01）;缝隙连接蛋白Cx43表达增多,而p-Cx43减少。结论：黄芪注射液可有效改善阿霉素导致的心肌损伤,其机制可能与黄芪注射液抑制ADR诱导的内质网应激及缝隙连接蛋白磷酸化有关。     

不同剂量阿霉素致大鼠局灶节段硬化肾病模型的建立比较

目的探讨不同剂量阿霉素对大鼠局灶节段硬化肾病模型的影响。方法左侧肾切除加尾静脉注射不同剂量阿霉素致大鼠肾脏局灶节段性硬化,观察不同剂量阿霉素对模型大鼠成活率、24 h尿蛋白定量、血清肌酐、尿素氮、肾脏病理的影响。结果不同阿霉素注射剂量组大鼠4周、8周成活率随着注射剂量的升高呈逐渐下降趋势,且4周、8周时阿霉素注射剂量4.5～6 mg/kg组模型大鼠成活率均低于50%;8周时成活率与注射剂量呈高度显著性负相关（r=0.9045,P〈0.01）。各阿霉素注射剂量组于1周出现尿蛋白明显升高（P〈0.01）、2周出现血清肌酐明显升高（P〈0.01）、4周出现血清尿素氮明显升高（P〈0.01）,并均呈进行性增高,2周时除3 mg/kg组外,其余各组血清尿素氮较正常组高（P〈0.01,P〈0.05）;8周时各注射剂量组大鼠24 h尿蛋白定量、血清肌酐、血清尿素氮与阿霉素注射剂量呈高度显著性正相关（r=0.942 9,P〈0.01;r=0.938 4,P〈0.01;r=0.956 8,P〈0.01）。各组大鼠肾脏病理均提示肾小球出现局灶节段硬化表现,且硬化程度随注射剂量的增加而呈加重趋势。结论阿霉素尾静脉注射剂量3 mg/kg模型组大鼠死亡率低,同时大鼠肾脏病理又能表现出符合人类肾小球局灶节段硬化的改变,是较为理想的造模剂量。     

不同剂量链脲佐菌素腹腔注射制备大鼠糖尿病心肌病模型的病理学观察

建立糖尿病性心肌病（DCM）大鼠模型,观察不同剂量链脲佐菌素（STZ）单次腹腔注射后大鼠心肌和胰腺的病理学变化。用STZ 50 mg/kg、55 mg/kg、60 mg/kg 3种剂量单次腹腔注射,制备糖尿病大鼠模型;以柠檬酸三钠-柠檬酸缓冲液腹腔注射,作为对照。72 h后,测空腹血糖及做口服葡萄糖耐量实验（OGTT）;3周后,HE染色观察各组大鼠胰腺和心肌形态学变化,Masson三色染色观察心肌纤维化改变。OGTT和空腹血糖显示3组存活大鼠糖尿病均成模;3周末,50 mg/kg和55 mg/kg剂量死亡率为25%;60 mg/kg剂量高,达到75%;HE染色显示55 mg/kg剂量组大鼠胰岛明显萎缩,轮廓不清晰,胰岛细胞数量少,心肌细胞肥大、排列紊乱,细胞间隙增大,并有炎症细胞浸润;50 mg/kg组胰岛和心肌也有变化,但无55 mg/kg组明显。心肌Masson染色显示55 mg/kg组心肌内胶原组织明显增多,排列紊乱,分布不均。55 mg/kg剂量的STZ单次注射大鼠腹腔,造模3周可以建立较明显的DCM模型,可为DCM的组织病理学和实验研究提供一个较好的动物模型。     

蒙药新Ⅱ号对扩张型心肌病大鼠心功能、心肌细胞内质网应激及凋亡的作用

目的：探讨蒙药新Ⅱ号对阿霉素性扩张型心肌病大鼠心功能、心肌病理、心肌细胞内质网应激及凋亡作用。方法：30 只SD 雄性大鼠分为3组（n=10）： 正常对照组、模型组（腹腔注射阿霉素2 mg/kg体重,1次/周,用药4周后观察4周）和蒙药新Ⅱ号组（腹腔注射阿霉素2 mg/kg体重,1次/周,用药4周后,给予蒙药新Ⅱ号30 mg/kg·d灌胃,共4周）。观察大鼠的一般情况,8 周后行高频超声心动图检查,测定各项心功能指标,检查结束后处死大鼠,取心脏,行HE 染色、VG染色及电镜观察。用TUNEL 法检测各组大鼠心肌细胞凋亡, Western blot 检测各组大鼠心肌细胞内质网伴侣蛋白GRP78、GRP94及促凋亡因子CHOP、caspase-3表达。结果：与模型组相比较,①蒙药新Ⅱ号组大鼠心脏左室结构及血流动力学各项指标均有明显改善（P<0.05）。②蒙药新Ⅱ号组大鼠心肌病理积分明显下降（P<0.01）。③蒙药新Ⅱ号组大鼠心肌细胞内质网应激伴侣蛋白GRP78、GRP94、CHOP、caspase-3表达及细胞凋亡明显减少 （P<0.01）。结论：蒙药新Ⅱ号可改善扩张型心肌病大鼠心脏功能,减轻心肌病理变化,缓解内质网应激,减少心肌细胞凋亡。这一实验结果可能是蒙药新Ⅱ号治疗扩张型心肌病作用机制之一。     

敦煌疗风虚瘦弱方对大鼠慢性心衰的治疗作用及其机制

目的：观察敦煌疗风虚瘦弱方（LXD）对慢性心衰大鼠的治疗作用及机制。方法：48只Wistar雄性大鼠随机分为6组（n=8）：正常组、模型组、卡托普利组和LXD高、中、低剂量组。除正常组外,其余各组大鼠尾静脉注射阿霉素（2.5 mg/kg）,每周1次,连续6周复制慢性心衰模型,末次注射阿霉素60 min后,卡托普利组灌胃卡托普利,LXD高、中、低剂量组分别以灌胃LXD水煎液80、40、20 g/kg （生药/体重）,正常组和模型组灌胃等容量生理盐水,每天1次,连续6周,同时每周腹腔注射15 mg/kg异丙肾上腺素1次。记录各组大鼠的呼吸、皮毛颜色、活动、体重、力竭游泳时间、心率（HR）、平均动脉压（MAP）、左室收缩压（LVSP）、左室舒张末压（LVEDP）、左室内压最大上升速率（+dp/dtmax）,左室内压最大下降速率（-dp/dtmax）,检测血清白介素-6（IL-6）及肿瘤坏死因子-α（TNF-α）水平,评价抗氧化活性和心室质量指数,光镜下观察心肌组织形态变化。结果：与正常组比较,模型大鼠体重增长减慢,力竭游泳时间明显缩短,心脏功能减弱,出现细胞因子激活、自由基损伤、心肌酶释放增多,HE染色显示心肌组织形态出现损伤,心肌纤维断裂等。与模型组比较,各剂量LXD对模型大鼠有不同程度的治疗作用,给药第42天,LXD各剂量组体重明显增长;LXD高、中剂量组力竭游泳时间明显延长（P<0.05）,MAP、血清IL-6、TNF-α、MDA、LVMI和RVMI显著降低（P<0.05,P<0.01）,LVSP、+dp/dtmax及-dp/dtmax均显著升高（P<0.05,P<0.01）,LXD高剂量组LVEDP显著降低（P<0.01）,LXD中、低剂量组CK和AST显著降低（P<0.05,P<0.01）;LXD各剂量组血清SOD升高。结论：敦煌疗风虚瘦弱方对阿霉素诱导的慢性心衰模型大鼠具有一定的治疗作用,作用机制与改善血流动力学,降低心肌组织损伤有关。     

脂肪干细胞移植对野百合碱诱发的肺动脉高压大鼠肺动脉压的量效和时效作用

目的探索脂肪干细胞（ADSC）移植治疗野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠的适宜细胞数和干预时间。 方法（1）MCT的建模时效和量效：雄性SD大鼠48只分为正常对照组,20 mg/kg、30 mg/kg、40 mg/kg MCT组分别予腹腔注射生理盐水、MCT 20 mg/kg、30 mg/kg、40 mg/kg,4和8周后,右心室插管法检测平均肺动脉压（mPAP）,称重法计算右心室肥厚指数（RVHI）。（2）ADSC的治疗量效作用：雄性SD大鼠分别予腹腔注射MCT（30只）和生理盐水（30只）,1周后通过颈静脉注射分别移植0.5×10⁶、1.0×10⁶、3.0×10⁶、5.0×10⁶ADSC,其他组予等量生理盐水。移植3周后检测mPAP和RVHI。（3）ADSC的治疗时效作用：雄性SD大鼠30只,分别注射40 mg/kg MCT（24只）和生理盐水（6只）。MCT腹腔注射1 d,1、2周后分别移植1.0×10⁶个ADSC。MCT注射4周后检测mPAP和RVHI。多组间比较采用单因素或双因素方差分析,两两比较采用LSD检验。 结果（1）腹腔注射4周后,30 mg/ kg或40 mg/kg MCT组mPAP和RVHI均升高[mPAP值（24.89±3.31）mmHg,（27.19±2.11）mmHg比（15.80±0.42）mmHg,差异有统计学意义（P均< 0.05）;RVHI值0.42±0.06,0.47±0.04比0.25±0.02,差异有统计学意义（P均< 0.05）]。8周后,20 mg/kg或30 mg/ kg MCT组mPAP和RVHI均恢复正常,而40 mg/kg MCT组大鼠全部死亡。（2）40 mg/ kg MCT诱导的PAH大鼠mPAP和RVHI均升高。移植1.0×10⁶个ADSC可降低PAH大鼠的mPAP[（17.24±0.66）mmHg比（27.19±1.73）mmHg,P < 0.05]。移植0.5×10⁶、3.0×10⁶、5.0× 10⁶个ADSC不能降低PAH大鼠的mPAP和RVHI。（3）MCT腹腔注射1周和2周后,移植1.0×10⁶个ADSC可降低PAH大鼠的mPAP。 结论40 mg/kg MCT造模4周可建立稳定的PAH大鼠模型;造模1或2周后移植1.0×10⁶个ADSC能有效降低PAH大鼠的mPAP。     

葛根素对糖尿病心肌细胞的保护及其机制研究

观察葛根素（Puerarin）对链脲佐菌素（streptozotocin,STZ）诱导的糖尿病大鼠心肌细胞的保护作用,并探讨血小板反应素1（Thrombospondin-1,TSP-1）的表达改变及其作用。雄性SD大鼠45只随机分为三组（n=15）：糖尿病组和葛根素治疗组采用一次腹腔注射链脲佐菌素（STZ）65mg／kg制备糖尿病模型,其中葛根素治疗组于造模后葛根素腹腔注射4周（100mg/kg/day）,正常对照组仅腹腔注射等量生理盐水（6ml／kg）,同样喂养4周。四周后各组大鼠处死。H—E染色及透射电子显微镜观察三组大鼠心肌细胞纤维显微结构和超微结构的病理改变．免疫组化和实时荧光定量PCR法观察大鼠心肌细胞中TSP-1蛋白和mRNA表达的变化．同时利用Langendorff离体心脏灌流法测定各组大鼠心室肌细胞功能。结果发现葛根素治疗组较糖尿病组大鼠的体重增加明显,同时血糖下降,有显著性差异（P〈0．01）。H—E染色显示糖尿病大鼠多处心肌肌丝紊乱伴少量炎症细胞浸润,电镜下发现有线粒体嵴消失溶解,肌丝排列紊乱等病理改变,而葛根素治疗组大鼠偶见上述病理变化。免疫组化显示葛根素治疗组心肌内TSP-1阳性细胞密度小于糖尿病大鼠,TSP-1 mRNA表达也比糖尿病大鼠要低。此外葛根素治疗组大鼠的左室收缩末压（LVSEP）、左心室舒张末期压（LVEDP）等心功能指标均明显低于正常组（P〈0．01）,但较糖尿病组有显著改善（P〈0．01）。上述结果显示葛根素能保护糖尿病大鼠心肌细胞的高糖损伤和维持心室肌细胞的功能,而该机制可能与抑制心肌细胞TSP-1表达的水平有关。     

实验性2型糖尿病心肌病大鼠模型的建立与评价

目的建立和评价2型糖尿病心肌病（DC）大鼠模型,探究高糖脂饮食在模型建立中的作用。方法将雄性Wistar大鼠随机分成正常对照组、高糖脂饮食组和高糖脂负荷小剂量STZ组。高糖高脂膳食诱导11周负荷小剂量链脲佐菌素（STZ）（30 mg/kg）腹腔注射建立DC模型,并观察糖代谢、脂代谢和心功能的变化。结果①大鼠经高糖高脂饲料诱导4周后,与正常对照组相比,胆固醇（TCH）和甘油三酯（TG）均显著增高（P〈0.05）,血糖值没有明显变化（P〉0.05）。②大鼠注射30 mg/kg STZ后72 h,血糖水平开始升高,继续以高糖高脂饲料喂养6周后,与正常对照组比较,高糖脂饮食组和高糖脂负荷小剂量STZ组大鼠TG、TCH维持高水平,差异有显著性（P〈0.05）;高糖脂负荷小剂量STZ组大鼠血糖值持续高水平,与正常对照组差异有显著性（P〈0.001）。③心功能测量结果显示,高糖脂饮食组大鼠出现温和的心脏功能异常（左心室收缩压降低,左心室舒张末压升高）;高糖脂负荷小剂量STZ组大鼠左心室收缩和舒张功能均出现异常（LVSP、每搏输出量、心排量降低,LVEDP、左心室最大舒张速率升高）,但以舒张功能异常为主。结论大鼠高糖脂饮食诱导负荷小剂量STZ可建立类似临床症状的2型DC模型,高糖脂饮食在糖脂代谢紊乱和心脏功能损伤过程中有重要作用,结合糖、脂代谢指标和心脏功能指标可以有效简便评价糖尿病心肌病模型。     

间歇性低压低氧与连续性低压低氧对大鼠血液动力学作用的比较(英文)

本研究旨在探讨并比较慢性间歇性低压低氧（intermitten thypobaric hypoxia,IHH）和慢性连续性低压低氧（continuous hypobaric hypoxia,CHH）对大鼠血液动力学作用的影响。40只成年Sprague—Dawley大鼠随机分为5组：对照组（CON）,28天IHH处理组（IHH28）,42天IHH处理组（IHH42）,28天CHH组（CHH28）和42天CHH组（CHH42）。IHH火鼠于低压氧舱分别接受28或42天模拟5000m海拔高度低氧（11．1％O2）处理、每天6h。CHH处理大鼠生活在低压氧舱环境中,除每天半小时常氧供食、供水和清洁外,其余时间均分别接受时程为28或42天的模拟5000m海拔高度低氧（11．1％O2）处理。每周定时测定大鼠体重。通过导管法测定基础常氧和急性低氧状态下的血液动力学,包括半均动脉压（meanartery blood pressure,MAP）、心率（heartrate,HR）、左审收缩峰压（1eft ventricular systolic pressure,LVSP）、正负左率最人压力变化速率（maximum change rate of left ventricular pressure,&#177;LVdP／dtmax）。通过生物化学方法测定大鼠心肌超氧化物岐化酶活性和丙二醛含量。并分别测定全心、左心室和右心室重量。结果显示：（1）CHH42大鼠基础HR和MAP低于CON,IHH和CHH28大鼠（P〈0．05）。（2）IHH大鼠表现出明显的抗心肌缺氧／复氧损伤作用,表现为急性低氧状态下的HR、MAP、LVSP和＋LVdP/dtmax,改变明显低于CON大鼠（P〈0．05）;CHH大鼠表现出更为明显的抗急性低氧心脏保护作用,表现为急性低氧的HR、MAP、LVSP和&#177;LVdP/dtmax;改变明显低于CON和IHH火鼠（P〈0．05）,但出现复氧损伤作用,表现为复氧过程中血液动力学的恢复明显低于CON和IHH大鼠（P〈0．05）。（3）与CON大鼠相比较,IHH和CHH大鼠心肌抗氧化能力明显增强（P〈0．05,P〈0．01）。（4）与IHH和CON大鼠相比较,CHH大鼠表现明显的右心室肥厚（P〈0．01）。结果表明,IHH可诱导有效的心脏保护作用,而无明显的不良反应,因而具有潜在的实际应用价值。     

卡托普利对实验性2型糖尿病心肌病大鼠模型心脏保护作用

目的研究卡托普利对实验性2型糖尿病心肌病（T2DC）模型动物心脏保护作用和可能机制。方法以高糖脂饲料负荷30mg／kg剂量链脲佐菌素一次性腹腔注射建立T2DC大鼠模型,观察卡托普利45mg／kg灌胃给药6周对模型动物血糖和血脂水平,心脏功能和结构变化,心肌脂肪酸含量以及心肌组织过氧化物增殖体激活受体α（PPAR）和葡萄糖转运体4（GLUT4）基因表达等指标的影响。结果与T2DC大鼠模型比较,卡托普利给药后,左心室收缩压、左心室最大收缩速率、左心室最大舒张速率的绝对值和心输出量分别显著增加15％、77％、52％和54％（P〈0．05或P〈0．01）;室间隔厚度降低40％（P〈0．001）;血浆糖化血红蛋白和心肌组织游离脂肪酸含量分别降低31％和24％（P〈0．01,P〈0．05）;心肌组织PPARα基因表达显著降低（P〈0．05）,GLUT4基因表达显著增加（P〈0．05）。结论卡托普利可以显著改善T2DC模型动物心脏功能、抑制心室重构,其作用机制可能同调节与能量代谢相关基因表达、减轻心脏内脂肪积聚有关。     

氧化苦参碱对大鼠缺血再灌注心肌损伤的保护机制研究

目的:探讨氧化苦参碱(OMT)对大鼠缺血再灌注心肌损伤(MIRI)的保护机制。方法:随机将60只成年Wistar大鼠分成对照组、MIRI组和OMT组,每组20只,除对照组外,其他两组结扎30 min后松解结扎线灌注60 min。结扎前10 min,OMT组股静脉输入苦参注射液120 mg/kg,对照组、MIRI组则输入等容量生理盐水。造模后,记录两组心率(HR)、左心室收缩压(LVSP)、左室内压最大上升或下降速率(+dp/dt_(max)或-dp/dt_(min))及血清乳酸脱氢酶(LDH),检测两组心肌组织中一氧化氮(NO)、丙二醛(MDA)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)水平。结果:与MIRI组相比,OMT组HR、LVSP和+dp/dt_(max)、-dp/dt_(min)均显著升高(P0.05),且OMT组上述指标与对照组比较,差异均无统计学意义(均P0.05)。与MIRI组相比,OMT组的NO、NOS、SOD、GSH-PX水平均显著升高,而MDA、血清LDH水平显著降低,比较差异均有统计学意义(均P0.05),且OMT组上述指标与对照组比较,差异均无统计学意义(均P0.05)。结论:OMT对MIRI大鼠具有心肌保护作用,其机制可能与提高抗氧自由基活性、改善微循环及舒张冠脉血管有关。     

Oxysophoridine Protects Against Focal Cerebral Ischemic Injury by Inhibiting Oxidative Stress and Apoptosis in Mice

Our previous studies have demonstrated that oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation. In this study, we further investigated whether OSR could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. After reperfusion, neurological scores and infarct volume were estimated. Morphological examination of tissues was performed. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Oxidative stress levels were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and Western-blot analysis. OSR pretreatment groups significantly reduced infract volume and neurological deficit scores. OSR decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression. These findings indicate that OSR has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.     

Dantrolene protects erythrocytes against oxidative stress during whole-body irradiation in rats

In our study, we examined the radioprotective effects of dantrolene against gamma irradiation-induced damage of blood cells after total body irradiation of rats. Rats were divided into three groups of eight rats each. The first group was the control group receiving no dantrolene or irradiation, the second group received total body irradiation (RT) with 5 Gy of gamma irradiation only, and the third group received dantrolene at a dose of 5 mg x kg(-1) plus RT. Dantrolene was given intraperitoneally 30 min before RT. All groups were sacrificed 2 h after RT, and blood samples were taken. Leukocyte, and thrombocyte counts and hemoglobin levels were measured. Furthermore, malondialdehyde (MDA) levels in plasma and erythrocytes and superoxide dismutase (SOD) and glutathione peroxidase activities (GSH-Px) in erythrocytes were determined. It was found that pretreatment with dantrolene at a dose of 5 mg x kg(-1) significantly reduced the MDA levels and increased the antioxidant SOD and GSH-Px activities, and prevented the decrease in leukocyte and thrombocyte counts. We conclude that dantrolene has clear antioxidant properties when given prior to radiation exposure and the protective effect of dantrolene against damage inflicted by radiation, depends, at least in part, on the decrease in lipid peroxidation and increase in the activity of antioxidant enzymes SOD and GSH-Px.     

Antagonistic effect of scutellarin on the toxicity of selenium in rat livers

Selenium has both nutritional function and toxicity according to its concentration and species. To counteract the toxicity of selenium, scutellarin was investigated. Wistar rats were supplemented with 40 μg Se/kg/d as sodium selenite, 40 μg Se/kg/d with 20 mg/kg/d scutellarin, and 20 mg/kg/d scutellarin, respectively, for 15 d. The mRNA levels and activities of glutathione peroxidase (GSH-Px) and thioredoxin reductase (TR), and the malondialdehyde (MDA) contents were measured. Reactive oxygen species (ROS) were detected by chemiluminescence assay, and tissue conformation was investigated by histological study. The results showed significant decreases of mRNA levels and activities of GSH-Px and TR and a significant increase of MDA content in livers of the Se-treated rats (p<0.05, compared with the control). Supplementation of scutellarin to the Se-treated group significantly inhibited the decreases of mRNA levels and activities, and the increase of MDA content (p<0.05, compared with the Setreated group). Meanwhile, scutellarin-scavenged ROS generated in the mixture of sodium selenite, reduced glutathione, and oxygen. Liver injury was displayed in slices exposed to selenium at the present dose. The groups treated with both selenium and scutellarin or only scutellarin did not show significant tissue damage. Thus, scutellarin had an antagonistic effect against the toxicity of selenium.     

白芍总苷对心肌缺血再灌注大鼠内质网应激因子CHOP、GRP78、GRP94的表达及凋亡的影响

目的:研究白芍总苷(TGP)对心肌缺血再灌注(I/R)大鼠内质网应激因子CCAAT/增强子结合蛋白的同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)、葡萄糖调节蛋白94(GRP94)表达及凋亡的影响。方法:选择健康清洁级SD大鼠75只,根据随机数字表法分成5组,每组15只,分别记为假手术组、I/R组、50 mg/kg TGP组、100 mg/kg TGP组以及200 mg/kg TGP组。检测并对比各组大鼠CHOP、GRP78、GRP94水平,对比分析各组大鼠心肌I/R指标、梗死面积率以及心肌细胞的凋亡率。结果:I/R组和TGP各组的CHOP、GRP78及GRP94水平均明显高于假手术组,且TGP各组较I/R组明显更低(均P0.05)。100 mg/kg和200 mg/kg TGP组的CHOP、GRP78及GRP94水平均明显低于50 mg/kg TGP组,且200 mg/kg TGP组较100 mg/kg TGP组明显更低(均P0.05)。I/R组和TGP各组缺血30 min的T波改变、再灌注120 min的T波改变及LVEDP水平均明显高于假手术组,LVSP、+dp/dtmax及-dp/dtmax水平均明显低于假手术组(均P0.05)。与I/R组相比,TGP组缺血30 min的T波改变、再灌注120 min的T波改变及LVEDP水平呈剂量依赖型下降,而LVSP、+dp/dtmax及-dp/dtmax水平呈剂量依赖型上升(均P0.05)。I/R组和TGP各组的梗死面积率和心肌细胞的凋亡率均明显高于假手术组(均P0.05)。与I/R组相比,TGP组的梗死面积率和心肌细胞的凋亡率水平呈剂量依赖型下降(均P0.05)。结论:应用TGP能够明显降低MIRI大鼠内质网应激因子CHOP、GRP78、GRP94的表达,调节心肌缺血和再灌注相关标志物或临床参数的水平,显著减少心肌缺血和再灌注所致的心肌梗死面积率及细胞凋亡率。     

Heart protective effects and mechanism of quercetin preconditioning on anti-myocardial ischemia reperfusion (IR) injuries in rats

In this study, we investigated the effects and mechanism of quercetin preconditioning on anti-myocardial ischemia reperfusion (IR) injuries in vivo. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. SD rats were orally given quercetin 250 mg/kg. Myocardium apoptosis was determined with TUNEL staining. The biomarkers related to myocardial ischemia injury were determined. Simultaneously, hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), LV end-diastolic pressure (LVEDP) and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax). The oxidative stress indicators and inflammatory factors were also evaluated. Western blot method was used for analysis of PI3K, Akt, p-Akt, Bax and Bcl-2 protein expressions. The results showed that quercetin significantly reduced apoptosis rate, improved cardiac function, decreased levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Quercetin also restrained the oxidative stress related to myocardial ischemia injury as evidenced by decreased malondialdehyde (MDA), and elevated GSH, superoxide dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px), glutathione reductase (GR) activity. Meanwhile, the inflammatory cascade was inhibited as evidenced by decreased cytokines such as tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin-1β (IL-1β). Our results still showed that quercetin pretreatment significantly inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing the level of cleaved Bax, and increasing the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, quercetin pretreatment markedly increased the phosphorylation of Akt. Blockade of PI3K activity by LY294002, dramatically abolished its anti-apoptotic effect and lowered Akt phosphorylation level. It can be concluded that quercetin pretreatment was protected against myocardium IR injury by decreasing oxidative stress, repressing inflammatory cascade, inhibiting apoptosis in vivo and PI3K/Akt pathway involved in the anti-apoptotic effect.     

Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats

The purpose of this study is to examine the antiarrhythmic and antioxidant effects of tamoxifen, one of the selective estrogen modulators, in ovariectomized rats subjected to myocardial ischemia-reperfusion (I/R) injury. A month after ovariectomy, rats were divided into four groups: (I) ovariectomized controls without any treatment, (II) ovariectomized rats treated with vehicle dimethylsulfoxide (DMSO), (III)–(IV) ovariectomized rats treated with tamoxifen 1 or 10 mg/kg,sc daily for 14 days. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. The blood pressure (BP), heart rate (HR), electrocardiography (ECG) was recorded before and during the ischemia-reperfusion period. The blood levels of malondialdehyde (MDA), creatine kinase (CK), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and catalase (CAT) were measured after the rats were killed. Tamoxifen reduced the incidence of ventricular tachycardia (VT) on ischemia and reperfusion as well as the incidence and duration of reversible ventricular fibrillation (VF) on reperfusion. I/R injury caused a significant fall in GSH, GSH-Px as well as an increase in MDA and CK levels in the control group when compared to tamoxifen treated groups. The changes in levels of CAT and GR were however, not significant. In conclusion, our findings suggest that tamoxifen has cardioprotective effects against I/R injury in rats, likely its antioxidant properties.     

Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.     

Protection Against Adriamycin-Induced Cardiomyopathy by Carnosine in Rats: Role of Endogenous Antioxidants

The aim of this study was to investigate the effects of carnosine, a biological antioxidant, on the acute cardiac damage induced by a single dose of adriamycin in rats. The experimental design consisted of four groups: Control (saline, i.p.); carnosine (CAR; 10 mg/kg/day, i.p.); adriamycin (ADR; 16 mg/kg on the 14th day, i.p.); carnosine with adriamycin. Carnosine was given 2 weeks before and following adriamycin treatment. Blood samples were collected for analysis of plasma creatine kinase (CK) and plasma antioxidant enzymes, glutathione peroxidase (GSH-Px), Cu, Zn-superoxide dismutase (SOD), and catalase (CAT). The rats were then sacrificed, and the hearts were autopsied for hemodynamic study, ECG, and histopathological examination. Results showed that adriamycin produced evident cardiac damage revealed by hemodynamic change, histological alterations, decreased plasma antioxidant enzymes activities, and increased lipid peroxidation to the control value. Carnosine treatment led to significant attenuation of adriamycin-induced cardiomyopathy revealed by normalization of the LVDP, ST interval, CK, SOD, GSH-Px, CAT, and lipid peroxidation. An increase in oxidative stress and inactivation of SOD, GSH-Px, CAT by a single dose of adriamycin were prevented when carnosine was given 2 weeks before and on the same day adriamycin treatment was administered.