钙敏感受体对大鼠糖尿病性心肌病的影响

目的:观察钙敏感受体(Ca SR)在大鼠糖尿病性心肌病中的作用。方法:30只雄性Wistar大鼠随机分为对照组、糖尿病4周组和糖尿病8周组(n=10)。高糖高脂饮食4周后腹腔注射STZ(30 mg/kg)建立糖尿病模型。通过透射电镜观察心肌超微结构的变化,通过Western blot检测心肌组织Ca SR、肌浆网Ca2+-ATPase(SERCA)和受磷蛋白(PLN)的蛋白表达。结果:与对照组相比,随着病程的延长糖尿病组大鼠心肌Ca SR、SERCA蛋白表达降低,PLN表达增加,心肌结构损伤逐渐加重。结论:在大鼠糖尿病性心肌病进展过程中Ca SR的表达逐渐降低,并可能导致钙稳态紊乱参与糖尿病心肌病的发生。     

慢性癫痫大鼠心肌中钙敏感受体及丝裂原活性蛋白激酶表达的改变

目的：观察钙敏感受体在癫痫大鼠心肌细胞中的表达和丝裂原活化蛋白激酶途径的变化。方法：戊四氮成功点燃慢性癫痫模型;Wistar健康雄性大鼠随机分为5组：对照组;癫痫组;癫痫+精胺组;癫痫+精胺+Chalhex231组;癫痫+Chalhex231组,每组各12只。模型组用PTZ亚惊厥剂量（35 mg/kg）持续腹腔注射28 d后停药1周,再用相同剂量的PTZ测试,对照组以等容生理盐水代替PTZ 腹腔注射,依据Racine行为学分级标准出现连续5次出现Ⅱ级以上发作者视为成功点燃慢性癫痫模型;以钙敏感受体激动剂精胺,钙敏感受体抑制剂Chalhex231做为干预因素,（精胺3 μmol/L和Chalhex231 2 μmol/L）;检测血清肌酸激酶、肌酸激酶同工酶;检测心肌功能、大鼠心肌组织形态学变化、心肌细胞的超微结构、心肌中钙敏感受体以及细胞外调节蛋白激酶 ERK、 p-ERK、p-JNK表达情况。结果：与正常组比较,癫痫组CK、CK-MB含量明显升高,心脏超声显示心脏顺应性下降,左室功能降低,E/A<1。心肌细胞超微结构显示损伤严重。CaSR表达进一步增加,p-JNK蛋白表达增加,p-ERK蛋白表达减少。精胺能够促进癫痫所诱发的CaSR蛋白表达增多、p-JNK蛋白表达增加,p-ERK蛋白表达减少;Chalhex231的作用相反。结论：慢性癫痫可诱发心肌改变,CaSR表达增多可能参与癫痫慢性发作时心肌损伤,MAPK信号通路可能参与慢性癫痫心肌损伤过程。     

钙敏感受体通过JNK途径参与内毒素心肌损伤*

目的: 观察内毒素所致的心肌损伤中,钙敏感受体(CaSR)对c-Jun氨基末端激酶 (JNK)途径的影响。方法: 腹腔注射内毒素(5 mg/kg)制作新生大鼠内毒素心肌损伤模型,Wistar新生大鼠随机分为6组:对照组、内毒素组、CaSR激动剂组、CaSR抑制剂组、JNK抑制剂组、CaSR抑制剂+JNK抑制剂组。HE染色观察心肌形态, 测定血清乳酸脱氢酶(LDH)含量,PCR检测IL-6的mRNA表达,Western blot检测CaSR及JNK的蛋白表达。结果: 与对照组相比,内毒素组心肌损伤加重,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达均明显增加(P＜0.05)。与内毒素组比较,CaSR激动剂组心肌损伤加重,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达增加(P＜0.05); CaSR抑制剂组心肌损伤减轻,LDH含量、CaSR和JNK的蛋白表达减少(P＜0.05);JNK抑制剂组心肌损伤进一步减轻,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达均减少(P＜0.05);CaSR抑制剂+JNK抑制剂组心肌损伤明显减轻,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达进一步减少(P＜0.05)。结论: CaSR可能通过JNK途径参与内毒素所致的心肌损伤。     

黄酒多酚对糖尿病心肌病大鼠心肌细胞凋亡的影响

目的:探究黄酒多酚对糖尿病心肌病大鼠心肌细胞凋亡的影响。方法:将30只雄性SD大鼠随机分为空白对照组(Control组)、糖尿病心肌病组(DCM组)、糖尿病心肌病+黄酒多酚组(DCM+YWP组)(n=10)。采用单次腹腔注射65 mg/kg链脲佐菌素(STZ)构建糖尿病心肌病大鼠模型,对照组采用相同剂量的枸橼酸缓冲液进行单次腹腔注射,DCM+YWP组建模后用18 mg/kg黄酒多酚灌胃。12周后观察大鼠一般情况,用多普勒心超评价心脏结构和功能,用电镜观察心肌组织超微结构,用ELISA法检测心肌组织炎症指标,用氧化应激指标检测试剂盒检测心肌组织氧化应激水平,用Westen blot检测心肌组织凋亡相关蛋白Bax、Bcl-2和Caspase-3(cleaved)的表达水平。结果:与DCM组相比,DCM+YWP组大鼠血糖水平及体重未出现明显变化;心脏超声显示左室舒张末期直径,左室收缩末期直径降低(P0.05),而左室缩短率、左心室射血分数、E/A比值以及Ea/Aa比值均升高(P0.05);心肌组织肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)以及白介素6(IL-6)水平下降(P0.05);心肌组织氧化应激指标丙二醛(MDA)水平下降、超氧化物歧化酶(SOD)以及谷胱甘肽过氧化物酶(GSH-Px)水平上升(P0.05);心肌组织Bax、Caspase-3(cleaved)蛋白的表达水平降低(P0.05),Bcl-2蛋白的表达水平升高(P0.05)。结论:黄酒多酚能改善糖尿病心肌病大鼠的心脏功能,降低心肌组织炎症因子和氧化应激水平,抑制糖尿病心肌病大鼠心肌细胞凋亡。     

心肌梗死大鼠钙敏感受体表达与心肌细胞凋亡的变化

目的:观察大鼠急性心肌梗死后不同时间心肌钙敏感受体(CaSR)的表达和心肌细胞凋亡的变化情况。方法:健康Wistar大鼠随机分为假手术组(Sham)和心肌梗死(AMI)组,通过结扎左侧冠状动脉前降支的方法,建立大鼠心肌梗死模型,分别在手术后1、2、4周(每组成功存活n=5)检测心脏形态学和血流动力学的改变,检测心肌组织中CaSRmRNA和蛋白的表达,以及Bax、Bcl-2、caspase-3和caspase-9蛋白的表达,检测血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)活性和肌钙蛋白(cTnT)水平,观察心肌细胞凋亡情况。结果:和Sham组相比,随着心肌梗死的发展,AMI组大鼠心肌组织CaSR的mRNA和蛋白的表达、细胞凋亡指数均明显增加(P<0.05),心肌细胞超微结构损伤严重;左心室收缩压(LVSP)、左心室内压最大上升速率(+dp/dtmax)(mmHg/s)和最大下降速率(-dp/dtmax)(mmHg/s)减少,左心室舒张末期压(LVEDP)明显增大(P<0.05);AMI组血清cTnT水平、CK和LDH活性均升高(P<0.05),随着心肌梗死的发展,cTnT水平和CK活性逐渐降低,LDH变化不明显。心肌组织中促凋亡相关蛋白Bax、caspase-3、caspase-9表达增多,抑制凋亡的相关蛋白(或因子)Bcl-2表达减少(P<0.05)。结论:随着AMI的发展,AMI组大鼠心肌组织中CaSR的mRNA和蛋白的表达增多,细胞凋亡数增加,表明CaSR参与了心肌梗死的发展,其机制可能与促进细胞凋亡有关。     

厄贝沙坦对糖尿病大鼠心肌损伤中Notch1信号通路的影响

目的：观察厄贝沙坦对糖尿病大鼠心肌损伤的作用,分析Notch1信号通路在其中的变化。方法：实验分4组：正常对照组（CON）、高糖高脂组（HC）、糖尿病组（DM）和厄贝沙坦+糖尿病组（Ir+DM）。制作2型糖尿病（T2DM）大鼠模型成功后,第8周开始检测大鼠空腹血糖水平（FBG）、全心质量及左心室重量,计算心脏指数（H/B）及左室重量指数（LVWI）,检测大鼠血浆甘油三酯（TG）、胆固醇（TC）水平,检测心肌组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量变化,免疫组化检测Bcl-2、Bax表达变化,Western blot检测大鼠心肌组织Notch1、Hes-1及Jagged-1的蛋白表达。结果：与CON组相比,HC组H/B、LVWI、FBG无明显变化,血脂、MDA含量明显升高,SOD活性、Bcl-2/Bax及Notch1、Hes-1、Jagged-1蛋白表达降低;与HC组相比,DM组H/B、LVWI、FBG、MDA含量增加明显,血脂水平无明显变化,SOD活性、Bcl-2/Bax及Notch1信号通路蛋白表达进一步降低;与DM组相比,厄贝沙坦干预组H/B、LVWI明显降低,血脂、血糖水平无明显变化,但SOD活性、Bcl-2/Bax增加,MDA含量降低,同时Notch1信号通路相关蛋白表达增加。结论：糖尿病可导致大鼠发生心肌损伤,厄贝沙坦可能通过增强Notch1信号通路的表达发挥心肌保护作用。     

血糖波动对2 型糖尿病大鼠心肌组织形态的影响及机制研究

目的:观察血糖波动对2型糖尿病大鼠心肌组织形态的影响并探讨其可能机制。方法:选取45只雄性Sprague-Dawley(SD)大鼠,按随机数字法分成正常对照组(CON组)和糖尿病组(DM组)。DM组给予4周高糖高脂饲料喂养后,予小剂量链脲佐菌素35 mg/Kg腹腔注射建立2型糖尿病大鼠模型。将成模大鼠按随机数字法分成糖尿病对照组(CDM组)和波动血糖组(FDM组)。FDM组大鼠每天定时皮下注射短效胰岛素并错时给予葡萄糖,建立糖尿病血糖波动模型,CON组、CDM组予等量生理盐水皮下注射。每周测血糖值2天,4次/天,动态观测各组大鼠外形、进食量、饮水量等变化。造模成功12周后取腹主动脉血测定糖化血红蛋白(Hb Alc),取大鼠心脏组织行Masson染色观察心肌纤维化水平,免疫印记法分别检测心肌组织AKT、p-AKT蛋白的表达,免疫组织化学法分析各组大鼠心肌细胞中Caspase-3蛋白的表达。结果:(1)与CON组相比,FDM组、CDM组大鼠Hb A1c、血糖变异系数(CV)水平升高,差异具有统计学意义(P0.05);与CDM组相比,FDM组Hb A1c水平差异无统计学意义(P0.05),CV值进一步升高,差异具有统计学意义(P0.05)。(2)与CON组相比,CDM组、FDM组大鼠心肌组织形心肌纤维化水平升高,差异具有统计学意义(P0.05);与CDM组相比,FDM组心肌组织心肌纤维化水平进一步升高,差异具有统计学意义(P0.05)。(3)与CON组相比,FDM组、CDM组大鼠心肌p-AKT蛋白表达水平均减少,差异具有统计学意义(P0.05);与CDM组相比,FDM组p-AKT蛋白表达水平均进一步减少,差异具有统计学意义(P0.05)。而三组大鼠心肌组织AKT蛋白表达水平差异无统计学意义(P0.05)。(4)与CON组相比,FDM组、CDM组大鼠心肌Caspase-3蛋白表达水平均升高,差异具有统计学意义(P0.05);与CDM组相比,FDM组Caspase-3蛋白表达水平进一步升高,差异具有统计学意义(P0.05)。结论:血糖波动可加重2型糖尿病大鼠的心肌纤维化,其机制可能与抑制AKT活化有关。     

CaSR表达在大鼠糖尿病性肝硬化损伤和纤维化发生中的作用

目的:观察钙敏感受体(CaSR)在糖尿病性肝损伤发生中的作用。方法:本实验分别制备糖尿病大鼠和高糖处理HSC系大鼠肝星形细胞模型。40只Wistar大鼠随机分为正常对照组(Control,n=10),糖尿病组(T1D,STZ 60 mg/kg 一次性腹腔注射,n=30),造模成功后分别在2、4、8周检测大鼠的体重、血糖、血清中谷草转氨酶(AST)和谷丙转氨酶(ALT)活性,观察形态学和超微结构改变,以及Western blot检测CaSR和肝纤维化相关指标表达的变化。HSC系大鼠肝星形细胞随机分为正常对照组(Control,10% FBS-DMEM + 5.6 mmol/L葡萄糖),高糖组(HG,10% FBS-DMEM + 40 mmol/L葡萄糖下培养48 h)和CaSR抑制剂组(HG+Calhex₂₃₁,10% FBS-DMEM + 40 mmol/L葡萄糖 + 2.5μmol/L CaSR抑制剂(Calhex₂₃₁)下培养48 h,每组n=5)。结果:动物模型中,与正常组相比,糖尿病大鼠体重减轻,血糖、AST和ALT显著升高,CaSR和胶原Ⅰ(COⅠ)、胶原Ⅲ(COⅢ)、基质金属蛋白酶1(MMP1)、基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)蛋白表达上调;细胞模型结果与大体基本一致,与正常组相比,高糖组细胞分化标志性蛋白α-平滑肌肌动蛋白(α-SMA)表达增加,表明HSC分化成肌成纤维细胞,细胞外间质(ECM)主要成分COⅠ和COⅢ表达增加,降解ECM的关键酶MMP9同样增加,Calhex₂₃₁可减轻上述变化。结论:CaSR表达上调参与大鼠糖尿病性肝损伤和纤维化的发生。     

大鼠心肌重塑过程中Axin蛋白质的表达变化

为观察大鼠心肌重塑过程中Axin蛋白质表达水平的变化,实验用颈静脉输注去甲肾上腺素(NE)和动静脉造瘘(AVF)方法复制大鼠心肌重塑病理模型,采用超声心动术检测心脏结构和收缩功能。取病理模型大鼠左心室以及分离培养的成年大鼠心肌成纤维细胞,采用Wester blot技术检测Axin蛋白质的表达水平。结果观察到,在颈静脉输注NE 3d后,大鼠心脏发生向心性心肌肥厚和心肌纤维化,其左心室的Axin蛋白表达水平较对照组显著升高。A-V造瘘术一周后引起大鼠离心性心肌肥厚,心肌无明显纤维化,心肌Axin表达量与对照相比无显著变化。在分离培养的成年大鼠心肌成纤维细胞,NE处理24h能明显升高Axin蛋白的表达水平。上述结果表明,大鼠心脏有Axin蛋白质表达,NE致大鼠心肌重塑过程中Axin蛋白表达显著增加,可能与该过程的心肌纤维化有关。     

GDF11对Ⅱ型糖尿病小鼠心肌损伤的保护作用

目的观察GDF11对Ⅱ型糖尿病C57BL/6J小鼠心肌损伤的保护作用及心肌凋亡水平的变化情况。方法 60只体重20~25 g的雄性C57BL/6J小鼠,随机分为3个组:正常对照组(control)、II型糖尿病模型组(DM)和GDF11干预组(DM+GDF11)。高脂高糖饲料饲养4周后,连续3次腹腔注射60 mg/kg链脲佐菌素(STZ),建立II型糖尿病小鼠模型,持续高脂高糖饲料饲养4周后,小动物超声检测心功能,取心肌组织,TUNEL染色检测心肌组织凋亡比例,Western blot法检测凋亡相关蛋白cleaved-caspase-3、Bcl-2和Bax的表达。结果糖尿病损伤显著下调左室射血分数和左室短轴缩短率,增加心肌凋亡率,而给予重组GDF11蛋白能够明显改善心功能并减轻心肌凋亡。结论外源性的GDF11可以显著减轻糖尿病损伤后心肌凋亡水平,改善心功能。     

低浓度乙醇对糖尿病大鼠心肌损伤后线粒体融合素2表达的影响

目的：探讨低浓度乙醇对糖尿病大鼠心肌损伤后线粒体融合素2（mfn2）表达的影响。方法：糖尿病大鼠模型采用链脲佐菌素55 mg/kg腹腔注射,分为正常对照组（Control组）,糖尿病组（DM组）和糖尿病+乙醇组（DM+EtOH组）（n=6）;糖尿病+乙醇组于造模成功1周后给予2.5%乙醇日常饮用,1周后改为5%的乙醇持续至8周,8周后行离体心脏灌流,测定心室血流动力学指标,应用自动生化分析仪测定血清乳酸脱氢酶（LDH）和天门冬氨酸转移酶（AST）的水平。Western blot测定左心室组织线粒体融合素2（mfn2）蛋白表达,免疫组化测定心肌组织mfn2蛋白表达。结果：与control组大鼠心肌相比,DM组大鼠心率、左室发展压、左室做功下降,左室舒张末压抬高,血清LDH及AST升高明显,心室mfn2蛋白表达降低;与DM组大鼠心肌相比,DM+EtOH组明显促进心率、左室发展压、左室做功的恢复,降低左室舒张末压,同时降低LDH的水平和AST的释放,mfn2的蛋白表达增高。结论：糖尿病大鼠心肌损伤时,心肌mfn2表达降低;低浓度乙醇增强mfn2在心肌组织中的表达,提示mfn2的增加可能参与低浓度乙醇对糖尿病诱发的心肌损伤的保护作用。     

Cardiac fibrosis in diabetic rats: regulation and mechanism of activation of the PPARgamma signal pathway

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily which affects organic fibrosis. The aims of the study were to approach the effects of activation of the PPARgamma signal pathway on cardiac fibrosis in diabetic rats, and also the effects on cardiac remodeling and function. Type 1 diabetic models were used in the study. All the animals were divided into 3 groups: I: control group; II: diabetic group; III: diabetes+Pioglitazone (Piog, a PPARgamma ligand) administration group. After 14 weeks of feeding, general condition, fibrosis indices, echocardiography and interventricular pressures parameters were detected. At the 14th week, compared with group I, the hydroxyproline concentration in group II significantly increased, and CO I and III distribution was more obvious by sirius red staining. Reduction of LVSP (left ventricular systolic pressure) and increase of LVEDP (left ventricular end-diastolic pressure) were also significant in group II. But these situations were changed by the administration of Piog in group III. Furthermore, results of RT-PCR and immunohistochemistry showed that Piog administration reduced angiotensin II type 1 receptor (AT1-R) expression in diabetic models. Hence, activation of the PPARgamma signal pathway could repress cardiac fibrosis in diabetic rats, and partly improve cardiac remodeling and function by down-regulating activity of RAS at the receptor level.     

Exercise protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway in rats

To explore the protective effect of exercise training on the injury of myocardium tissues induced by streptozotocin (STZ) in diabetic rats and the relationship with endoplasmic reticulum stress (ERS), the male sprague-dawley (SD) rats were fed with high-fat and high-sugar diet for 4 weeks, followed by intraperitoneal injection of STZ, 40 mg/kg, to establish a diabetes model, and then 10 rats were randomly selected as diabetes mellitus (DM) controls and 20 eligible diabetic rats were randomized into two groups: low-intensity exercise training (n = 10) and high-intensity exercise training (n = 10). After 12 weeks of exercise training, rats were killed and serum samples were used to determine cardiac troponin-I (cTn-I). Myocardial tissues were sampled for morphological analysis to detect myocardial cell apoptosis, and to analyze protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12. Different intensities (low and high) significantly reduced serum cTn-I levels compared with the DCM group (p < 0.01), and significantly reduced the percentage of apoptotic myocardial cells and improved the parameters of cardiac function. Hematoxylin and eosin and Masson staining indicated that exercise training could attenuate myocardial apoptosis. Additionally, exercise training significantly reduced GRP78, CHOP, and cleaved caspase-12 protein expression in an intensity-dependent manner. These findings suggest that exercise appeared to ameliorate diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in diabetic rats.     

姜黄素衍生物B06对2型糖尿病大鼠心肌的保护作用及其机制探讨

目的：研究姜黄素衍生物B06对2型糖尿病大鼠心肌的保护作用及机制。方法：雄性sD大鼠35只,随机均分为正常对照组（NC组）、高脂组（肿组）、高脂治疗组（rT组）、糖尿病组（DM组）和糖尿病治疗组（DT组）（n=7）,后四组高脂喂养4周后,DM组及七rr组用低剂量链脲佐菌素（srz）诱导糖尿病,FTr组和町组用0．2mg／kg·d的姜黄素衍生物B06灌胃。用生化方法测大鼠血糖和血脂浓度,用ELISA法测血胰岛素水平,并计算胰岛素抵抗指数,用光镜和电镜观察心肌形态,用Westernblot法测心肌腺苷酸活化蛋白激酶a（AMPKa）和磷酸化腺苷酸活化蛋白激酶a（p-AMPKa）的蛋白表达。结果：HF组及DM组血糖、血脂、血胰岛素、胰岛素抵抗指数升高,经B06治疗后均下降;HF组及DM组AMPKa和p-AMPKa表达下降,经／306治疗后升高;DM纽心肌间质胶原纤维增多,心肌细胞内线粒体扩张,经B06治疗后病变减轻。结论：B06可缓解2型糖尿病大鼠心肌病变,AMPKa和p-AMPKa表达升高可能参与其中。     

Decreased RhoA expression in myocardium of diabetic rats

Diabetic cardiomyopathy is 1 of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 +/- 7 beats/min in diabetic rats. There was a 62% decrease (p < 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 +/- 6.7 x 106 molecules/microg total RNA) compared with controls (101 +/- 10.3 x 106 molecules/microg total RNA). Western blot showed a 33% decrease in total RhoA protein expression in heart tissues of diabetic rats compared with controls (p < 0.05). A reduced RhoA translocation in heart tissues of diabetic rats was determined by a 64% decrease in membrane-bound RhoA (p < 0.01 vs. control group), indicating that the activation of RhoA is markedly reduced in diabetic myocardium. Our data suggest that down-regulated RhoA may be involved in cardiomyopathy in diabetic rats.     

Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats

ABSTRACT: BACKGROUND: Recent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats. METHODS: Male SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve weeks later, echocardiography was conducted, and blood samples were collected for counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming growth factor beta (TGF-beta), and CD31 levels in the myocardium were determined by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of collagen type , collagen type , and Picrosirius Red staining were performed, and cardiomyocyte cross-sectional area was measured. RESULTS: After 12 weeks STZ injection, blood glucose increased significantly and remained consistently elevated. EPO treatment significantly improved cardiac contractility and reduced diastolic dysfunction. Rats receiving the EPO injection showed a significant increase in circulating EPCs (27.85+/-3.43%, P < 0.01) compared with diabetic untreated animals. EPO injection significantly increased capillary density as well as EPOR and VEGF expression in left ventricular myocardial tissue from diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and reduced TGF-beta expression. CONCLUSIONS: Treatment with EPO protects cardiac tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading to improved revascularization and the inhibition of cardiac fibrosis. Key words: erythropoietin; vascular endothelial growth factor; diabetes mellitus; endothelial progenitor cell; myocardial interstitial fibrosis; transforming growth factor beta.