肥厚心肌缺血后适应时细胞外信号调节激酶的保护作用

目的 研究缺血后适应(IPost)在离体小鼠肥厚心肌缺血再灌注(L/R)损伤中的保护作用,探讨细胞外信号调节激酶(ERK1/2)在此保护中的作用机制.方法 12周龄C57/BL小鼠通过主动脉弓缩窄4周建立心肌肥厚模型,利用Langendorff灌流装置建立小鼠肥厚心肌I/R模型,30 min全心缺血随后再灌注120 min.分为4组,I/R组、Ipost组(采取缺血10 s及再灌注10 s的3次IPost周期)、I/R+PD98059组(ERK1/2抑制剂)、Ipost+PD98059组,进行心脏血流动力学、心肌梗死范围检测,Western印迹方法检测细胞外信号调节激酶(ERK1/2)、Bcl-2、Bax、细胞色素C(Cyt.c)蛋白表达水平,脱氧核苷酸转移酶介导的生物素原位缺口末端标记(TUNEL)法检测心肌细胞的凋亡.结果 与I/R组比较,IPost组小鼠心脏血流动力学指标左心室收缩压、左心室压力变化最大速率显著改善[(85±4)mm Hg比(68±5)mm Hg,(3811±230)mm Hg比(2830±230)mm Hg,均P<0.05],IPost组心肌的ERK1/2磷酸化水平、Bcl-2、线粒体Cyt.C表达显著增加,Bax、胞质Cyt.C蛋白表达显著降低,凋亡指数显著降低,心肌梗死范围减小(均P<0.05).与I/R组比较,I/R+PD98059组上述指标差异均无统计学意义(均P>0.05).IPost+PD98059组显示在再灌注的最初15 min使用PD98059能消除IPost对肥厚心肌的上述保护作用并显著增加心肌梗死面积,与I/R组水平相同.结论 IPost能有效地减轻离体小鼠肥厚心肌缺血再灌注损伤,ERK1/2细胞信号途径参与IPost对缺血再灌注肥厚心肌保护作用并可能通过其抗凋亡的机制实现.     

阿托伐他汀对兔心肌缺血再灌注诱导细胞凋亡的影响

目的探讨阿托伐他汀对兔心肌缺血再灌注诱导的细胞凋亡及Bcl-2、Bax蛋白表达的影响。方法30只雄性大白兔,随机分为假手术组(sham组)、缺血再灌注组(I/R组)及缺血再灌注加阿托伐他汀组(I/R AT组)。采用结扎、开放兔冠状动脉的方法,制作兔心肌缺血再灌注模型(缺血40min,再灌注2h),采用原位末端标记法(TUNEL法)检测心肌细胞凋亡情况,采用免疫组织化学法检测心肌中Bcl-2、Bax蛋白的表达情况。结果①I/R组凋亡指数明显大于sham组(P<0.01),而I/R AT组凋亡指数较I/R组显著减少(P<0.01)。②I/R组及I/R AT组Bcl-2蛋白表达百分率显著高于sham组(均P<0.01),且I/R AT组的Bcl-2蛋白表达也较I/R组明显上调(P<0.01);I/R组及I/R AT组的Bax蛋白表达明显强于sham组(均P<0.01),但I/R AT组的Bax蛋白表达弱于I/R组(P<0.01)。结论阿托伐他汀可以抑制心肌缺血再灌注诱导的细胞凋亡,减少心肌细胞凋亡数目,其机制可能与其上调心肌缺血再灌注时Bcl-2蛋白的表达、抑制Bax蛋白的表达有关。     

钙蛋白酶活化在小鼠心肌缺血再灌注损伤中的作用

目的:探讨钙蛋白酶在小鼠心肌缺血/再灌注(Ischemia/Reperfusion,I/R)损伤中的作用。方法:采用结扎/松解左冠状动脉前降支的方法建立小鼠心肌I/R模型。将实验动物随机分为假手术组、I/R组(冠状动脉结扎45 min,再灌注3h)及PD+I/R组(I/R前30 min静脉注射钙蛋白酶抑制剂-PD150606 1 mg/kg)。再灌注结束后,测定各组心肌梗死面积、细胞色素C含量、caspase-3活性。结果:与I/R组相比,PD150606预处理组心肌梗死区域面积明显减小,且PD150606能明显抑制由I/R引起的细胞色素C含量及caspase-3活性增加。结论:钙蛋白酶活化介导的心肌细胞凋亡在小鼠心肌I/R损伤中发挥了重要的作用。     

大鼠心肌缺血再灌注时心肌细胞凋亡情况及缺血预处理对其影响

目的探讨缺血再灌注及缺血预处理对大鼠缺血再灌注心肌细胞凋亡的影响.方法制备大鼠缺血预处理(IP)、缺血再灌注损伤(I/R)模型,采用末端脱氧核苷酸转换酶介导的生物素平移缺口末端标记技术(TUNEL)检测心肌细胞凋亡情况;同时检测心肌梗死范围.结果I/R组细胞凋亡率(43.37±4.82%)高,IP组虽然也有一定的心肌细胞凋亡率(24.53±2.95%),但较I/R组明显降低(P＜0.001).IP组心肌梗死范围较I/R组明显减小.结论心肌缺血再灌注损伤可诱发或加重心肌细胞凋亡,IP能明显减少缺血再灌注诱导的心肌细胞凋亡的发生率,能明显减少心肌梗死范围,减轻缺血再灌注损伤;IP能减少心肌梗死范围、减轻缺血再灌注损伤的机理可能与其能明显减少心肌细胞凋亡有关.     

MicroRNA-451对大鼠心肌缺血/再灌注损伤的影响

目的:探讨MicroRNA(miR)-451在大鼠心肌缺血/再灌注(I/R)损伤中的作用及其作用机制。方法:将70只SD大鼠随机分为5组:假手术组(SO)、缺血再灌注组(I/R)、腺病毒空载体组(I/R+Ad-GFP)、miR-451上调组(I/R+Ad-miR-451)、miR-451下调组(I/R+Ad-asmiR-451)。心肌注射病毒液(1×1010 pfu/只)或PBS液(150μl/只)后3d建立缺血30min再灌注24h的心肌I/R模型。应用TTC+伊文思蓝双染法测定各组心肌梗死面积百分比,TUNEL法检测凋亡率,Western Blot法测定HMGB1和Caspase 3活化片段含量,应用试剂盒检测血清CK、LDH含量以及心肌组织SOD、MDA含量。结果:再灌注24h后,与SO组相比,I/R组和I/R+Ad-GFP组血清CK、LDH含量明显升高,心肌组织SOD活性降低、MDA含量升高,心肌组织HMGB1及Caspase-3活化片段蛋白含量显著上升,心肌细胞凋亡指数明显增加(以上P<0.05);与I/R组、I/R+Ad-GFP组相比,I/R+Ad-miR-451组血清CK、LDH含量显著下降,心肌组织SOD活性上升、MDA含量下降,心肌组织HMGB1和Caspase-3活化片段蛋白含量下降,心肌梗死面积百分比降低,心肌细胞凋亡指数降低(以上P<0.05);与I/R组、I/R+Ad-GFP组相比,I/R+Ad-asmiR-451组血清CK、LDH含量无明显上升,心肌组织MDA含量及SOD活性无明显变化,心肌组织HMGB1表达含量无明显上升,心肌梗死面积百分比及心肌细胞凋亡指数无显著升高(以上P>0.05),Caspase-3活化片段蛋白含量上升(P<0.05)。结论:MicroRNA-451通过调控HMGB1的表达,减轻凋亡和氧化应激进而减轻心肌I/R损伤。     

STAT3在大鼠心肌缺血再灌注损伤中的作用

目的 探讨转录活化因子3 (STAT3)在大鼠心肌缺血再灌注损伤中的作用.方法 将健康成年雄性SD大鼠18只分为3组(n=6):假手术组(S组),只分离左冠状动脉,不结扎;缺血/再灌注组(I/R组),结扎左冠状动脉前降支30 min,再灌注120 min;缺血/再灌注+STAT3抑制剂Stattic组(ST组),于再灌注前10 min经尾静脉注射STAT3特异性抑制剂Stattic 500μg/kg.再灌注结束时,取缺血区心肌标本,采用红四唑(TTC)染色检测心肌梗死面积;采用原位末端缺口标记法(TUNEL法)检测细胞凋亡指数;采用Western-blot检测磷酸化STAT3(p-STAT3)、Fas蛋白表达;采用RT-PCR检测p-STAT3、Fas的mRNA表达;采用免疫组织化学法检测半胱氨酸天冬氨酸蛋白酶3 (Caspase-3)表达.结果 与S组相比,I/R组心肌梗死面积、心肌细胞凋亡指数、p-STAT3和Fas的蛋白及其mRNA表达、Caspase-3表达水平均增高(P＜0.05);与I/R组比较,ST组心肌梗死面积、心肌细胞凋亡指数升高(P＜0.05),p-STAT3蛋白及mRNA表达水平下调,Fas蛋白及mRNA表达、Caspase-3表达水平增加(P＜0.05).结论 STAT3可能通过调控Fas系统,从而有效的抑制Caspase-3凋亡系统对心肌细胞及箕其他组织的损伤.     

参附注射液对缺血再灌注心肌细胞凋亡的影响

目的:探讨参附注射液对大鼠缺血再灌注心肌细胞Bax、Bcl2及Fas蛋白表达的影响及它们与心肌细胞凋亡的内在联系。方法:健康SD大鼠36只随机分为3组,空白对照组(S组)、缺血再灌注+生理盐水组(I/R组)、缺血再灌注+参附注射液组(SF组),每组12只。采用钳闭左冠状动脉前降支制备心肌缺血再灌注模型。免疫组化检测Bax、Bcl2及Fas蛋白的表达,每组选24个视野分别测量光密度值(OD值)。TUNEL法检测凋亡心肌细胞并计算凋亡指数。结果:I/R组BaxOD值明显高于S组(P<0.01),SF组BaxOD值明显低于I/R组(P<0.01),且低于S组(P<0.05)。I/R组Bcl2OD值高于S组(P<0.05),且SF组Bcl2OD值高于S组(P<0.01),但I/R组与SF组比较差异无显著性。I/R组FasOD值明显高于S组(P<0.01),且明显高于SF组(P<0.01)。I/R组细胞凋亡指数明显高于S组和SF组(P<0.01),而SF组高于S组(P<0.05)。结论:参附注射液增加心肌Bcl2蛋白的表达,降低Bax及Fas蛋白的表达,抑制心肌细胞凋亡,保护缺血再灌注心肌。     

瑞舒伐他汀预处理影响小鼠心肌缺血再灌注炎症因子和细胞凋亡

目的:探讨瑞舒伐他汀预处理对小鼠心肌缺血/再灌注后炎症因子的影响及其可能的心肌保护机制.方法:C57小鼠72只随机分为3组:假手术组(Sham组)、心肌缺血/再灌注组(MI/R组)、心肌缺血/再灌注+瑞舒伐他汀预处理组(MI/R+R组);建立小鼠MI/R模型;ELISA法检测血清高敏C反应蛋白(hs-CRP)和肿瘤坏死因子-α(TNF-α)的含量,Evansblue/TTC染色测定心肌梗死面积,TUNEL染色检测心肌细胞凋亡.结果:MI/R+R组的hs-CRP和TNF-α含量明显低于MI/R组(P＜0.01).MI/R+R组与MI/R组相比,心肌梗死面积明显减少(P＜0.05),心肌细胞凋亡显著减轻(P＜0.05).结论:瑞舒伐他汀可能通过减少炎症因子合成或释放,进而抑制心肌细胞凋亡,减轻小鼠心肌缺血/再灌注损伤.     

大鼠心肌IP对I/R心肌细胞凋亡及bcl-xl蛋白表达的影响

目的研究缺血预适应(ischemic preconditioning,IP)对大鼠缺血再灌注(ischemia/reperfusion,I/R)心肌细胞凋亡和凋亡抑制基因bcl-xl蛋白表达的影响.方法采用末端脱氧核苷酸转移酶介导的带萤光的dUTR缺口末端标记(TUNEL)法和免疫组化方法.结果 IP组TUNEL法阳性心肌细胞核数量及阳性心肌细胞核占总心肌细胞核数的百分比均明显少于I/R组(P<0.05或0.01);IP组表达bcl-xl蛋白阳性的心肌细胞数及阳性心肌细胞占心肌细胞总数的百分比均明显高于I/R组(P<0.01) .结论大鼠心肌IP能够显著减少I/R心肌细胞凋亡;IP通过上调凋亡抑制基因bcl-xl基因表达可能是其减少I/R心肌细胞凋亡的机制之一.     

芪参益气滴丸对大鼠心肌缺血再灌注损伤的作用机制研究

探讨芪参益气滴丸（QS）对大鼠心肌缺血再灌注时,心肌细胞尿路上皮癌胚抗原1（UCA1）长链非编码RNA、凋亡及凋亡相关基因表达的影响。方法结扎SD大鼠冠状动脉左前降支,造成心肌缺血40 min后剪断结扎线,再灌注120 min,复制实验性心肌缺血再灌注模型,将36 只大鼠随机分为假手术组（只穿刺不结扎,Control 组）、缺血再灌注组（I/R 组）、QS 干预组（QS+I/R 组）,术后采用原位末端标记法检测心肌细胞凋亡指数,采用荧光定量聚合酶链反应分析并检测3 组大鼠心脏组织中UCA1 的表达,Western blot 检测p27 蛋白表达水平。结果QS+I/R组的细胞凋亡数与I/R 组比较,差异有统计学意义（p <0.05）;与I/R 组比较,QS+I/R 组UCA1 整体表达水平上升,而p27 蛋白减少（ p<0.05）;并且UCA1 与p27 蛋白的表达呈负相关。结论QS 能降低大鼠缺血再灌注心肌细胞凋亡率,其可能通过上调UCA1 水平,减少p27 蛋白表达,保护损伤的心肌细胞。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.