格列齐特对糖尿病大鼠心肌的保护作用及其机制*

目的: 观察格列齐特对糖尿病大鼠心肌保护作用及其可能的机制。方法: 将60只健康SD大鼠随机分为正常组(NC,n=10),造模组(n=50)给予高糖高脂饲料4周后,腹腔注射STZ(45 mg/kg)建立糖尿病大鼠模型,随机抽取以FBG≥16.7 mmol/L作为糖尿病模型建立成功。将造模成功的38只糖尿病大鼠随机分为模型组(MC,n=9)、格列齐特组(Glic,80 mg/kg,n=10)、格列本脲组(Glib,2.5 mg/kg,n=10)、法舒地尔组(Fas,10 mg/kg,n=9);NC组和MC组灌胃等容积蒸馏水,Glic组和Glib组灌胃给药,Fas组采用腹腔注射。各组大鼠每天给药一次,每周记录体质量及空腹血糖(FBG),持续8周。实验结束时取血并测定心脏质量,计算心脏质量指数(HWI);测定各组糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)含量以及血清丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性;通过HE和Masson染色,观察心肌病理变化和组织胶原纤维水平;TUNEL染色观察并计算心肌细胞凋亡率;Western blot法检测心肌组织中RhoA、ROCK1、eNOS、Bcl-2和Bax蛋白表达。结果: 与NC组比较,MC组FBG、HWI、HbA1c、TC、TG、LDL-C、MDA水平,心肌组织胶原沉积和心肌细胞凋亡率以及心肌组织中RhoA、ROCK1、Bax蛋白明显升高,SOD活性及HDL-C、eNOS、Bcl-2和体重显著降低(P＜0.01);与MC组相比,Glic组FBG、HWI、HbA1c、TC、TG、LDL-C和MDA等指标明显下降,心肌组织胶原沉积及心肌细胞凋亡减轻,心肌组织RhoA、ROCK1、Bax蛋白表达下调(P＜0.01或P＜0.05),大鼠体重和血清中SOD活性,HDL-C升高,eNOS、Bcl-2蛋白水平升高(P＜0.01或P＜0.05)。与Glic组相比,Glib组与Fas组体重、血脂、FBG、HWI、MDA以及心肌纤维化和心肌细胞凋亡水平升高,SOD和Bcl-2降低,Glib组心肌组织RhoA、ROCK1、Bax蛋白表达上调(P＜0.01或P＜0.05)。结论: 格列齐特可改善糖尿病大鼠心肌损伤并减轻心肌细胞凋亡水平,其机制可能与降低血糖,改善氧化应激状态,调控RhoA/ROCK1/eNOS信号通路有关。     

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。     

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48h)和CaSR抑制剂组(HG+Calhex₂₃₁,10%FBS-DMEM+40mmol/L葡萄糖+2.5μmol/L CaSR抑制剂(Calhex₂₃₁)下培养48h,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(C...     

葛根素对2型糖尿病大鼠的治疗作用*

目的:观察葛根素对2型糖尿病(T2DM)大鼠的治疗作用。方法:采用高糖高脂饲料喂养加一次性腹腔注射60 mg/kg链脲佐菌素的方法建立T2DM 大鼠模型,随机分为正常组,模型组,二甲双胍(40 mg/kg)组,葛根素低、中、高剂量(40,80,160 mg/kg)组,每组10只大鼠;造模成功后,灌胃给药4周,每周测量大鼠体重和空腹血糖(FBG),末次给药24 h后取血,收集血清,检测各组大鼠的血糖、血清甘油三酯(TG)、总胆固醇(TC) 、低密度脂蛋白-胆固醇(LDL-C)水平、高密度脂蛋白-胆固醇(HDL-C),血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)活性,血清尿素氮(BUN)、肌酐(SCr)、尿酸(UA)水平。结果:干预4周后,与正常组比较,模型组大鼠体重显著降低(P＜0.01),FBG,TC,TG,LDL-C,ALT,AST,BUN,SCr,UA均显著升高(P＜0.01),而HDL-C 显著降低(P＜0.01);与模型组比较,二甲双胍组和葛根素各剂量组大鼠体重均显著增加(P＜0.01),FBG,TC,TG,LDL-C,ALT,AST,BUN,SCr,UA均显著降低(P＜0.01),而HDL-C显著升高(P＜0.01)。结论:葛根素能够减少T2DM大鼠体重降低幅度,降低血脂、血糖水平,可用于T2DM的治疗。     

压力超负荷性心肌肥厚大鼠心肌细胞核钙转运的改变

通过腹主动脉缩窄(abdominalaorticcoarctation ,AAC)心肌肥厚大鼠模型制备、差速离心提纯心肌细胞核、酶学方法测定Ca2 +-ATPase活性、45Ca2 +同位素法测定核钙摄取和荧光分光光度计测定细胞核内自由钙浓度 ,初步揭示压力超负荷心肌肥厚大鼠心肌细胞核钙转导异常的环节。结果发现 :心肌细胞核上存在具有[Ca2 +]和ATP依赖性的高亲和力Ca2 +-ATPase ,以[Ca2 +]依赖的方式摄取45Ca2 +,并呈先升高后降低趋势。AAC术后4周大鼠心肌显著肥厚 ,伴有明显的血流动力学异常 ,与对照组比较 ,AAC大鼠心肌细胞核Ca2 +-ATPase活性减少51.93 %(p<0.001) ,但核45Ca2 +摄入量(核外[Ca2 +]浓度为800 -1600nmol/L时)和核内[Ca2 +](核外[Ca2 +]浓度为0 -1000nmol/L时)均明显增加(p<0.05) ;正常组离体心肌细胞核Ca2 +摄取受PKA刺激(p<0.05) ,而被PKC抑制剂和CaM抑制剂显著抑制(p<0.05) ,AAC大鼠心肌细胞核Ca2 +摄取仅受CaM抑制剂抑制(p<0.01) ,而PKA和PKC抑制剂对其无明显影响(p>0.05)。结论为心肌肥厚时 ,心肌细胞核Ca2 +转运系统及其磷酸化调节可能发生改变。     

Iuteolin对糖尿病大鼠心脏功能的保护作用及其可能机制

目的：研究Iuteolin对链脲佐菌素诱导的Ⅰ型糖尿病大鼠心功能及心肌线粒体氧化应激的影响。方法：雄性SD大鼠,随机分成正常对照组,Iuteolin对照纽,糖尿病模型组,低剂量Iuteolin（10ms／（kg·d））灌胃治疗组,高剂量Iuteolin（100ms／（kg·d））灌胃治疗组。各组大鼠饲养8周后,测体重、血糖、心功能、左心室重量、心肌胶原含量及活性氧自由基（ROS）水平,分离心肌线粒体检测ROS水平、超氧化物歧化酶（SOD）活性及线粒体肿胀程度。结果：Iuteolin处理对糖尿病大鼠血糖无明显影响,但可减少糖尿病引起的体重下降。高剂量Iuteolin可显著减小糖尿病大鼠心室与体重比值,提高左室发展压,降低左室舒张末压。高剂量Iuteolin治疗后,糖尿病大鼠心肌ROS及胶原含量。心肌线粒体ROS水平与肿胀程度均明显下降,心肌线粒体SOD活性明显增加。结论：Iuteolin处理可显著改善糖尿病大鼠心功能．其机制可能与减轻心肌线粒体氧化应激及抑制线粒体肿胀有关。     

GK糖尿病大鼠生物学特性观察

目的了解2型糖尿病模型GK大鼠生长曲线、主要脏器重量、糖代谢等生物学特性,评价GK大鼠葡萄糖刺激的胰岛素分泌能力。方法采用51只雄性GK大鼠及15只年龄性别匹配的Wistar大鼠作为研究对象。测定13周龄GK、Wistar大鼠空腹血糖、23周龄GK大鼠空腹及随机血糖。随访GK及Wistar大鼠生长曲线,34～46周龄期间血糖、糖化血红蛋白。46周龄时行腹腔葡萄糖耐量实验（IPGTT）,计算相关参数评价β细胞葡萄糖刺激的胰岛素分泌能力;之后处死大鼠,脏器称重。比较GK及Wistar大鼠间上述各指标差异。结果13周龄GK大鼠空腹血糖4．74±0．41mmol／L,对照Wistar大鼠1．85±0．44mmol／L（P〈0．001）。23周龄GK大鼠空腹血糖7．88±1．96mmol／L,随机血糖9．91±3．52～13．46±4．13mmol／L。7～20及34～45周龄期间GK大鼠体重高于对照Wistar大鼠（P〈0．05）,46周龄时无显著性差异。34～45周龄期间GK大鼠空腹血糖、进食后血糖、HbAlc均高于对照Wistar大鼠（P〈0．05）。IPGTT曲线下面积分析示GK大鼠胰岛素曲线下面积（AUCi）、葡萄糖曲线下面积（AUCg）高于对照Wistar大鼠,胰岛素与葡萄糖曲线下面积比值（AUCi／AUCg）低于对照Wistar大鼠,差异均有显著性（P〈0．05）。GK大鼠肾脏重量高于对照Wistar大鼠（P〈0．05）,余主要脏器重量差异无显著性。结论GK大鼠空腹血糖、进食后血糖、HbAlc水平升高,葡萄糖刺激的胰岛素分泌能力（GSIS）减退,葡萄糖刺激后胰岛素分泌早期相消失,晚期相代偿性增加,具有2型糖尿病特点;体重、血糖等生物学特性稳定。     

动脉粥样硬化大鼠心肌梗死时钙敏感受体表达的变化及其作用机制

目的:探讨动脉粥样硬化大鼠心肌梗死时钙敏感受体表达的变化及其作用机制。方法:Wistar大鼠随机分为4组:正常对照组(Control);异丙肾上腺组(ISO);动脉硬化组(AS);动脉硬化+异丙肾上腺素组(AS/ISO)。采用腹腔注射VD3和高脂饮食及大剂量异丙肾上腺素(ISO 200 mg/kg)皮下注射复制大鼠在体动脉粥样硬化心肌梗死模型,应用RT-PCR测定心肌组织中Ca SR、Bax、Bcl-2和caspase-3 m RNA的表达变化;TUNEL染色观察心肌细胞凋亡情况;光镜观察心肌形态学变化;紫外分光法检测血清肌酸激酶(CK)、电化学免疫发光法检测肌钙蛋白T(c Tn T)水平。结果:与正常组比较,ISO组CK活性、c Tn T水平以及Ca SR、Bax和caspase-3的表达均增加,同时Bcl-2表达减少,心肌细胞损伤严重,AS/ISO的心肌损伤进一步加重。结论:Ca SR的表达增多参与了动脉硬化大鼠心肌梗死的发生,其机制可能与促进心肌细胞凋亡有关。     

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。     

2型糖尿病大鼠的尿液代谢组学改变

目的 通过检测2型糖尿病大鼠尿液代谢谱的变化.探讨代谢组学在糖尿病研究中的应用.方法 SD大鼠高糖高脂饲料喂养6周后,腹腔注射链脲菌素(Streptozotocin,STZ)37 mg/kg建立2型糖尿病模型,动态检测空腹血糖(FBG)变化,检测甘油三酯(TC)、总胆固醇(TC)、游离脂肪酸(FFA)及胰岛素(INS)...     

八肽胆囊收缩素对大鼠心功能的影响及受体机制

为探讨八肽胆囊收缩素 (CCK 8)对麻醉大鼠心功能的影响及受体机制 ,实验监测了左心室收缩压(LVP)、左心室收缩与舒张期内压变化的最大速率 (±LVdp/dtmax)、心率 (HR)和平均动脉压 (MAP)。结果如下 :小剂量CCK 8(0 4 μg/kg)可引起心动过速 ,MAP、LVP和±LVdp/dtmax轻度上升 ;中剂量CCK 8(4 μg/kg)和大剂量CCK 8(4 0 μg/kg)可引起心动过缓 ,MAP、LVP和±LVdp/dtmax显著增加 ;应用CCK 受体 (CCK R)拮抗剂丙谷胺 (1 0mg/kg)抑制以上变化 ;由逆转录 聚合酶链反应 (RT PCR)检测到心肌组织有CCK A受体 (CCK AR)和CCK B受体 (CCK BR)mRNA表达。以上结果提示 :CCK 8可激活心肌组织的CCK R ,引起剂量依赖性的心功能增加和心率改变。     

Improvement in cardiac function of diabetic rats by bosentan is not associated with changes in the activation of PKC isoforms

We previously demonstrated that chronic treatment with the mixed endothelin A and B (ET_A and ET_B) receptor blocker bosentan improved isolated working heart function in streptozotocin (STZ) diabetic rats. Endothelin-1 (ET-1) peptide levels, ET-1 mRNA and ET_A and ET_B receptor mRNA were all increased in diabetic hearts, but were unaffected by bosentan treatment, indicating that the beneficial effects of bosentan on heart appear to be on downstream effectors of ET-1 and ET receptors rather than the ET-1 system itself. Stimulation of ET-1 receptors leads to increased activation of protein kinase C (PKC), which is associated with PKC translocation from the cytosol to the membrane. Persistent activation of specific PKC isoforms has been proposed to contribute to diabetic cardiomyopathy. The purpose of this study was to determine whether chronic treatment with bosentan influences the activation of PKC isoforms in hearts from diabetic rats. Male Wistar rats were divided into four groups: control, bosentan-treated control, diabetic, and bosentan-treated diabetic. Diabetes was induced by the intravenous injection of 60 mg/kg streptozotocin. One week later, treatment with bosentan (100 mg/kg/day) by oral gavage was begun and continued for 10 weeks. The heart was then removed, homogenized, separated into soluble (cytosolic) and particulate (membrane) fractions and PKC isoform content in each fraction was determined by Western blotting. PKC α, β2, δ, ε and ζ were all detected in hearts from both control and diabetic rats. However, no change in the levels or distribution between the soluble and particulate fractions of any of these isoforms could be detected in chronic diabetic hearts compared to control, whether untreated or treated with bosentan. These observations indicate that bosentan does not improve cardiac performance in STZ diabetic rats by affecting the activation of PKC isoforms.     

Propionyl-L-carnitine effects on postischemic recovery of heart function and substrate oxidation in the diabetic rat

Previous studies have shown that propionyl-L-carnitine (PLC) can exert cardiac antiischemic effects in models of diabetes. In the nonischemic diabetic rat heart, PLC improves ventricular function secondary to stimulation in the oxidation of glucose and palmitate. Whether this increase in the oxidation of these substrates can explain the beneficial effects of PLC in the ischemic reperfused diabetic rat heart has yet to be determined. Diabetes was induced in male Sprague-Dawley rats by an intravenous injection of streptozotocin (60 mg/kg). Treatment was initiated by supplementing the drinking water with propionyl-L-carnitine at the concentration of 1 g/L. After a 6-week treatment period, exogenous substrate oxidation and recovery of mechanical function following ischemia were determined in isolated working hearts. In aerobically perfused diabetic hearts, compared with those of controls, rates of glucose oxidation were lower, but those of palmitate oxidation were similar. Diabetes was also characterized by a pronounced decrease in heart function. Following treatment with by propionyl-L-carnitine, however, there was a marked increase in rates at which glucose and palmitate were oxidized by diabetic hearts and a significant improvement in heart performance. Postischemic recovery of function in diabetic hearts was also improved with PLC. This improvement in contractile function was accompanied by an increase in both glucose and palmitate oxidation. Our findings show that postischemic diabetic rat heart can be improved following chronic PLC treatment. This beneficial effect of propionyl-L-carnitine can be explained, in part, by an improvement in the oxidation of glucose and palmitate.     

Apela improves cardiac and renal function in mice with acute myocardial infarction

Apela was recently identified as a new ligand of the apelin peptide jejunum (APJ) receptor. The purpose of this study was to investigate the role of apela in post‐myocardial infarction (post‐MI) recovery from cardiorenal damage. A murine MI model was established, and apela was then infused subcutaneously for two weeks. Echocardiographs were performed before and after infarction at the indicated times. Renal function was evaluated by serum and urine biochemistry. Immunohistochemistry of heart and kidney tissue was performed by in situ terminal deoxynucleotidyl transferase‐mediated dUPT nick end‐labelling reaction. Compared to the control group (MI/vehicle), the average value of the left ventricular ejection fraction in apela‐treated mice increased by 32% and 39% at 2‐ and 4‐week post‐MI, respectively. The mean levels of serum blood urea nitrogen,creatinine, N‐terminal pro‐brain natriuretic peptide and 24‐hour urine protein were significantly decreased at 4‐week post‐MI in apela‐treated mice relative to that of control animals. At the cellular level, we found that apela treatment significantly reduced myocardial fibrosis and cellular apoptosis in heart and kidney tissue. These data suggest that apela improves cardiac and renal function in mice with acute MI. The peptide may be potential therapeutic agent for heart failure.     

替米沙坦改善糖尿病大鼠肾脏功能机制研究

目的研究替米沙坦对糖尿病大鼠24 h尿蛋白、血肌酐、肌酐清除率(Ccr)和血清尿素氮(BUN)等相关代谢指标的影响,且应用基因芯片探讨替米沙坦改善肾功能的机制。方法 30只SD大鼠,其中随机选取10只为正常对照组(给予等体积生理盐水)。选用20只大鼠,采用STZ法制备糖尿病模型,而后将16只造模成功的糖尿病大鼠随机分为替米沙坦治疗组(给予10 mg/kg/d的替米沙坦,n=8)和糖尿病模型组(给予等体积生理盐水,n=8)。三组大鼠均连续灌胃12周。每4周测定大鼠空腹血糖(FBG)和体重。12周末测定大鼠24h尿蛋白、尿肌酐、血肌酐和BUN水平。12周末处死大鼠,取肾脏组织进行基因芯片实验,并运用real time PCR进行验证。结果糖尿病模型组24h尿蛋白(P<0.01)、血肌酐(P<0.05)和BUN(P<0.01)比对照组显著升高,Ccr较对照组显著降低(P<0.05)。替米沙坦能改善糖尿病大鼠24h尿蛋白、血肌酐、Ccr和BUN水平。基因芯片结果显示替米沙坦组较糖尿病模型组有1541个基因发生显著改变,其中554个上调,987个下调。基因富集分析显示这些差异表达基因集中在氧化磷酸化通路和PPAR通路。Real time PCR证实替米沙坦组较糖尿病模型组ATP合成酶β亚基(Atp5b)、细胞色素c氧化酶亚基VIc(Cox6c)和NADH脱氢酶(辅酶Q)铁硫蛋白3(Ndufs3)基因显著下调。结论替米沙坦能有效改善糖尿病大鼠肾脏功能。替米沙坦的肾脏改善作用可能是通过线粒体氧化磷酸化通路和PPAR-γ通路调节。     

AdipoRon对2型糖尿病小鼠的治疗及其可能的肝脏机制

目的：观察口服脂联素受体激动剂（AdipoRon）对2型糖尿病小鼠的治疗效果及对肝脏的影响。方法：40只SPF级雄性C57/BL6小鼠随机分为正常对照组和实验组,实验组给予高糖高脂饲养联合腹腔注射小剂量链脲佐菌素建立二型糖尿病（T2DM）小鼠模型,随机分为模型对照（DM）组,低剂量AdipoRon治疗（DM+L）组,高剂量AdipoRon治疗（DM+H）组（n=10）。检测血清中丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）的变化;HE染色镜下观察肝细胞形态学变化;实时定量荧光PCR法检测肝脏中肝糖类相关基因（PEPCK）的表达。结果：与DM组小鼠比较,DM+H组和DM+L组小鼠ALT、AST、ALP、甘油三酯（TG）、葡萄糖（GLU）水平均降低（P<0.05）;与DM组小鼠比较,DM+H组小鼠和DM+L组小鼠血清游离脂肪酸（FFA）浓度显著下降（P<0.05）,而肝组织葡萄糖-6-磷酸酶（G-6-P）活性DM+L组小鼠显著下降,DM+H组小鼠无显著差异;与DM组小鼠比较,DM+H组小鼠肝组织磷酸烯醇式丙酮酸羧激酶（PEPCK） mRNA表达显著降低（P<0.05）,而DM+L组小鼠无显著差异。结论：给予AdipoRon治疗的小鼠血糖降低,ALT、AST、ALP的水平及G-6-P和PEPCK的表达下降,表明AdipoRon对2型糖尿病具有显著的治疗效果,对糖尿病小鼠肝脏有一定的保护作用。     

Lack of insulin impairs Mg2+ homeostasis and transport in cardiac cells of streptozotocin-injected diabetic rats

Serum and tissue Mg(2+) content are markedly decreased in diabetic patients and animals. At the tissue level, Mg(2+) loss progresses over time and affects predominantly heart, liver and skeletal muscles. In the present study, alterations in Mg(2+) homeostasis and transport in diabetic cardiac ventricular myocytes were evaluated. Cardiac tissue and isolated cardiac ventricular myocytes from diabetic animals displayed a decrease in total Mg(2+) content that affected all cellular compartments. This decrease was associated with a marked reduction in cellular protein and ATP content. Diabetic ventricular myocytes were unable to mobilize Mg(2+) following beta-adrenergic receptor stimulation or addition of cell permeant cyclic-AMP. Sarcolemma vesicles purified from diabetic animals, however, transported Mg(2+) normally as compared to vesicles from non-diabetic animals. Treatment of diabetic animals with exogenous insulin for 2 weeks restored ATP and protein levels as well as Mg(2+) homeostasis and transport to levels comparable to those observed in non-diabetic animals. These results suggest that in diabetic cardiac cells Mg(2+) homeostasis and extrusion via beta-adrenergic/cAMP signaling are markedly affected by the concomitant decrease in protein and ATP content. As Mg(2+) regulates numerous cellular enzymes and functions, including protein synthesis, these results provide a new rationale to interpret some aspects of the cardiac dysfunctions observed under diabetic conditions.     

西格列汀对糖尿病小鼠心肌重构和自噬的影响及其机制

目的: 探讨西格列汀对糖尿病小鼠心肌重构和自噬的影响和可能的机制。方法: 10周龄的C57小鼠腹腔注射STZ 50 mg/(kg·d),连续注射5 d,7 d测血糖浓度＞16.7 mmol/L视为糖尿病小鼠造模成功,造模成功4周后给与药物干预。本实验分四组,对照组(control, 腹腔注射等体积的缓冲液, n=10)、模型组(Streptozocin, STZ腹腔注射诱导糖尿病模型,n=8)、处理组(在模型组基础上给与西格列汀灌胃10 mg/(kg·d),n=8)、抑制剂组(在处理组的基础上给与腹腔注射Compound C (AMPK通路抑制剂,10 mg/(kg·d),n=8),对照组腹腔注射等体积缓冲液,6周后称体重,处死,取小鼠心脏并分离心室称重,计算心室/体重比,HE染色观察心肌细胞形态,Masson染色观察纤维化程度,Western blot 检测心肌脑钠肽(BNP)、转化生长因子β(TGF-β)、缝隙连接蛋白43(Cx43)、AMP依赖的蛋白激酶(AMPK)、LC3B蛋白表达。结果: 给药6周后,与对照组相比,模型组小鼠体重没有明显改变,心室/体重比明显增加(P＜0.05),苏木素-伊红(HE)染色显示细胞增大,Masson染色显示心肌间隙纤维化增多,BNP、TGF-β蛋白明显升高,Cx43、LC3B、AMPK蛋白下降(P＜0.05)。与模型组相比,西格列汀组BNP、TGF-β蛋白明显下降,Cx43、LC3B、AMPK蛋白增多(P＜0.05)。然而Compound C会抑制Cx43、LC3B、AMPK蛋白表达的上调(P＜ 0.05)。结论: 西格列汀可以改善糖尿病小鼠心肌肥厚和纤维化,并且可以通过AMPK相关通路调节Cx43和自噬。     

高糖高脂饮食联合注射STZ制备2型糖尿病大鼠缺血性心脏病模型

目的：制备2型糖尿病缺血性心脏病大鼠模型。方法：雄性Wistar大鼠20只,随机分为正常组和糖尿病模型组（n=10）。糖尿病模型组给予高糖高脂饮食饲喂4周后,一次性腹腔注射链脲佐菌素40mg/kg,制备糖尿病大鼠模型。每周常规监测血糖、血清胰岛素、体重的变化。糖尿病模型组与正常组大鼠,使用BL-41O生物机能试验系统,每周测定肢体2导联心电图。最后检测血清中的肌酸激酶和乳酸脱氢酶的含量。结果：高糖高脂饲料饲喂4周后胰岛素升高至4．05ng/ml,糖尿病模型组注射SIZ后空腹血糖迅速升高,达到17．9mmol/L。在第14周,糖尿病模型组出现S-T段抬高,并且与正常组比较,血清肌酸激酶（creatine kinase,CK）和乳酸脱氢酶（lactate dehydrogenase,LDH）均升高。结论：本实验成功建立的2型糖尿病缺血性心脏病大鼠模型,为研究糖尿病缺血性心脏病提供理想的动物模型。