Effect of mild hypothermia on the oxidative stress induced myocardlal injury after cardiopulmonary resuscitation北大核心CSCD

Objective To observe the effects of mild hypothermia on the myocardial mitochondrial injmy induced by oxidative stress after restoration of spontaneous circulation (ROSC) in rat of cardiac arrest model. Methods Eighteen male Wistar rats were randomly (raudom number) divided into normal temperature group and mild hypothermia group after ROSC. Ultrasound was used to measure the left ventricular ejection fraction (EF), shortening fraction (FS) and stroke volume (SV). The levels of glutethione (GSH), malondialdehyde (MDA) and adenosine triphosphate (ATP) in myocardium were detected. The ultramicroscopic structure of myocardial mitochondria was observed under transmission electron microscope at 4 h after ROSC. Results There were no significant differences in basic life support (BIS) time, dosage of epinephrine and number of defibrillation attempt between two groups (P > 0.05). The concentrations of GSH and ATP in myocardium of rats in hypothermia group were significantly higher than those in normal temperature group, while the level of MDA was significantly lower in hypothermia group than that in normal temperature group. Echocardiographic findings showed that hypothermia could significantly improve the EF, FS and SV after ROSC. The hypothermia decreased the myocardial mitochondria injury rather than normothermia [mitochondrial injury score: (0. 21 ±0.04) vs. ( 0.42 ±0. 08), P <0. 05]. Conclusions In this model, mild hypothermia can decrease myocardial oxidative stress injury, improving the cardiac function after ROSC.     

The effect of allicin on the ventricular myocytes of rabbit with heart failure北大核心CSCD

Objective To observe the effect of allicin on the action potential duration (APD) and L-type calcium current (ICa, L) in the ventricular myocytes of rabbits with heart failure in order to explore the mechanisms of therapeutic effect of allicin on cardiac arrhythmias complicated with heart failure. Methods Forty-five New Zealand White male rabbits were randomly (random number) assigned to 3 groups (n=15 in each group): sham operated group (sham group), heart failure group (HF group), and heart failure treated with allicin group (HF+AU group). The rabbit heart failure model was established by abdominal aortic constriction coupled with aortic regurgitation, the ventricular myocytes were obtained by enzyme double digestion, and the whole cell clamp was used to record action potential and calcium current.The action potential duration (APD), ICa, L and gating mechanism were observed during heart failure and allicin administered. Data were processed with pCLAMP version 10.2. Statistical analysis was performed using SPSS 17.0. Comparisons among groups were carried out using ANOVA, and SNK-g was used for multiple comparison as post-hoc. Results (1) Prolonged APD was found during heart failure, APD50 was prolonged from (93.4±4.7) ms in sham group to (115.5±6.2) ms in HF group (P<0.01). After administration of allicin 30 umol/L, APD50 was shortened to (105.2±5.5) ms (P<0.05). (2) The density of ICa, L increased during heart failure, peak current density increased increased from (-8.4±0.6) pA/pF in sham group to (-15.1±1.1) pA/pF while 0 mV attained at depolarizations (P<0.01). After administration of allicin 30 μmol/L, the current density reduced to (-10.1±0.8) pA/pF (P<0.01). The effect of allicin presented in both voltage dependent and consentration dependent manner. (3) According to the gating mechanism study, the main mechanism of lowering the density of ICa, L by allicin after heart failure was the acceleration of the steady inactivation of the channel, and the de-escalation of the recovery kinetic after the inactivation of the channel. Conclusions Allcin can be used to reduce the calcium current of ventricular myocytes in animal heart failure model, it has the potential of clinical use in treating cardiac arrhythmias during heart failure. © 2018 Chinese Medical Association. All rights reserved.     

Effect of kn93 on delayed afterdepolarization and calcium ion in ventricular myocytes of rabbits with heart failure北大核心CSCD

Objective To observe the effect of KN93, a CaMK II inhibitor, on delayed afterdepolarization (DAD) and calcium ion in ventricular myocytes of rabbits with heart failure, and to investigate the effect of CaMK II signaling pathway on trigged arrhythmia after heart failure. Methods Thirty male New Zealand White rabbits were randomized(random number) into the sham operated group (sham group), heart failure group (HF group) and heart failure with KN93 group (HF+KN93 group) (n=10 each group). The rabbit heart failure model was established by abdominal aortic constriction combined with aortic valve regurgitation. The ventricular myocytes were isolated by double enzyme digestion. The action potential and the transient inward current (/J were recorded by the whole-cell patch-clamp. The intracellular calcium transient was measured by the ion concentration measurement system. The main calcium transporter protein was detected by Western blotting. Data were analyzed by pCLAMP10.2. Statistical analysis was performed using SPSS 17.0. Comparisons among groups were conducted using ANOVA, and SNK-? multiple comparison procedure was utilized for post-hoc analysis. Results (1) After induction of heart failure, DAD and increment of trigger activity (TA) were observed in rabbit ventricular myocytes. Treatment of K.N93 with 1.0 nmol/L reduced the events of DAD and TA. (2) After induction of heart failure, Iti densities were increased from -0.12±0.02 pA/pF to -0.95±0.06 pA/pF at the polarization potential of -50 mV (n=10, /><0.01). The current densities were reduced to -0.44±0.04 pA/pF after application of 1.0 nmol/L of KN93 (=10, P<0.01). (3) KN93 led to decrement of intracellular calcium ion concentration and calcium transient amplitude, and acceleration of the decay process of calcium transient. (4) KN93 upregulated the expression of pPLN and SERCA2a, increased the uptake of intracellular calcium ion, downregulated the expression of NCX, decreased the Iti, and reduced the occurrence of DAD and TA. Conclusions KN93 can reduce the intracellular calcium ion concentration of the heart failure animal model, and the occurrence of the DAD and TA. CaMK II may be a new therapeutic target for arrhythmias in the heart failure. © 2018 Chinese Medical Association. All rights reserved.     

诊断超声联合微泡对骨髓间充质干细胞移植改善兔心肌缺血灌注的研究

Objective To explore the value of diagnostic ultrasound mediated microbubble destruction in improving the myocardial perfusion and left ventricular systolic function when cooperated with the mecsenchymal stem cells(MSCs) transplantation in rabbit myocardial ischemia. Methods One week after myocardial ischemia (MI) modeling,36 rabbits were divided into 3 groups,the control group(group Ⅰ) ,intravenous injection of MSCs group(group Ⅱ) and ultrasound + microbubble + MSCs group (group Ⅲ). Myocardial contrast enhancement (MCE) was performed and quantification analysis of anterior wall was assessed with Photoshop. Left ventrieular systolic function was assessed with M-mode echocardiography and bi-plane Simpson's method. CD34 expression in heart was detected with immunohistochemisty(IHC). Western blotting was applied to detect the level of VEGF in three groups. Results The differences of gray scale analyzed with histogram of Photoshop in anterior wall of ischemia myocardium between the group Ⅰ and group Ⅱ or group Ⅲ were significant,and P value was 0. 032 and 0. 000 , respectively. There were significant differences of FS between group Ⅲ (30. 43±4.09)% and group Ⅱ (26.29±2.93)%, P<0.01, and similar to group Ⅰ (19.28 ± 2.84)%. The difference of EF(%) between group Ⅲ and group Ⅱ was significant [(61.5±5.8 vs 53.6±4. 71), P<0. 05] ,or markedly significant between group Ⅲ and group Ⅰ [(61.5±5.8 vs 42.6± 5.0), P <0.01]. EF(%) assessed with bi-plane Simpson's method was significantly increased from (34.64 ± 4.59) in group Ⅰ to (41.78 ± 4.21) in group Ⅱ and (48.6±3.96) in group Ⅲ. The expression of CD34 assessed with immunohistochemistry was the highest in group Ⅲ. The level of VEGF with western blotting in group Ⅲ was significantly higher than other two groups. Conclusions It is an efficacious transplantation means of MSCs infusion under the ultrasound mediated microbubles destruction in improving the myocardial perfusion and cardiac systolic function.     

老年急性心肌梗死不同时间窗溶栓效果的观察

Objective To compare the effect of thrombolytic therapy on acute myocardial patients when it is given at different times after the onset of heart attack symptoms. Methods A total of 120 patiens with acute myocardial infarction were divided into two groups;an early group and a late group. The early group were the pa-tients who had begun to receive the therapy less than 6 hours after the onset of their symptoms, and the late group were the patiens who had begun to receive the therapy more than 6 hours after the onset of their symptoms. In ac-cordance with standard thrombolytic therapy practice, urokinase 1500000U was administered intravenously. Re-suits 5 h group vascular recanalization rate, the mortality rate after four weeks, the incidence of serious heart failure, six months after the left ventricular ejection fraction (LVEF) were 71.67%, 3.33%, 6. 67%, (63± 8.1) % ; the delayed group vascular recanalization rate, mortality rate four weeks, the incidence of serious heart failure, LVEF after six months were 15.0% , 13.33%, 12.0% , (51.5±9.5) %. There was significant differ-ence between the two groups in this respect(P<0.01 ,P<0.05) ,but it should be noted that there was no sig-nificant difference in the rate of heamorrage between the two groups (P>0.05 ). Conclusion The<5 h group showed much better results. , not only both vascular recanalization rate and the LVEF were significantly higher than in the delayed group, but also the mortality rate after four weeks was much lower too.     

老年急性心肌梗死不同时间窗溶栓效果的观察

Objective To compare the effect of thrombolytic therapy on acute myocardial patients when it is given at different times after the onset of heart attack symptoms. Methods A total of 120 patiens with acute myocardial infarction were divided into two groups;an early group and a late group. The early group were the pa-tients who had begun to receive the therapy less than 6 hours after the onset of their symptoms, and the late group were the patiens who had begun to receive the therapy more than 6 hours after the onset of their symptoms. In ac-cordance with standard thrombolytic therapy practice, urokinase 1500000U was administered intravenously. Re-suits 5 h group vascular recanalization rate, the mortality rate after four weeks, the incidence of serious heart failure, six months after the left ventricular ejection fraction (LVEF) were 71.67%, 3.33%, 6. 67%, (63± 8.1) % ; the delayed group vascular recanalization rate, mortality rate four weeks, the incidence of serious heart failure, LVEF after six months were 15.0% , 13.33%, 12.0% , (51.5±9.5) %. There was significant differ-ence between the two groups in this respect(P<0.01 ,P<0.05) ,but it should be noted that there was no sig-nificant difference in the rate of heamorrage between the two groups (P>0.05 ). Conclusion The<5 h group showed much better results. , not only both vascular recanalization rate and the LVEF were significantly higher than in the delayed group, but also the mortality rate after four weeks was much lower too.     

The effect of Ulinastatin on autophagy and apoptosis in the acute paraquat poisoning rats lung cellular北大核心CSCD

Objective: To investigate the effects of ulinastatin on autophagy and apoptosis of lung cells in rats with acute paraquat poisoning. Methods: A total of 150 Wistar rats were randomly (random number) divided into three groups. The rats in control group had stomach lavaged once with 1 mL of normal saline followed by intraperitoneal injection of 1 mL normal saline twice a day. PQ poisoning model was produced by stomach lavaged once with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline once a day. In PQ + ulinastatin (PU) group, UTI in dose of 12 000 U/kg was intraperitoneally injected in rats twice a day. The lung tissue was obtained on the 7th day after modeling, and the histopathological changes were observed under microscope after hematoxylin and eosin (HE) staining. The positive expressions of autophagy-related LC3 protein LC3 and Bcl-2 pretein in lung tissue were observed after immunohistochemistry staining, and the levels of LC3, Bax, Bcl-2 proteins were determined by Western blot. Results HE staining Results showed: it was observed from the PQ poisoning group that the abnormal cellular structure, enlargement in the pulmonary alveoli, leaking a lot of inflammatory cells, increased thickness of the alveoli wall and bleeding in the local area of lung tissue. Compared with the PQ poisoning group, the above changes in ulinastatin groups were relieved. Western blot Results showed; compared with the control group, the protein expressions of LC3-A/B were significantly increased in PQ poisoning group [LC3-A/B expression (A scale):0.22 ±0.05 vs. 0.14±0.03, F = 22.48, P < 0.01]. compared with PQ group, the expression of LC3 A/B obviously increased in the group of PU [LC3-A/B expression (A scale): 0.36 ± 0.08 vs. 0.22 ± 0.05, F = 22.78, P < 0.01]. compared with Con group, the expression of Bcl-2/Bax obviously decreased in the group of PQ [Bcl-2/Bax expression (A scale), 0.11 ± 0.04 vs. 0.83 ± 0.09, F = 154.43, P < 0.01]. Compared with PQ poisoning group, the protein expressions of Bcl-2/Bax were obviously increased in PU groups [Bcl-2/Bax expression (A scale): (0.63 ± 018) vs. (0.11 ± 0.04), F = 154.43, P < 0.01]. Immunohistochemistry result; compared with Con group, the expression of LC3 and Bcl-2 obviously decreased in the group of PQ [LC3 expression (A scale); (78.34±10.71) vs. (117.58 ±15.26), F =31.63, P < 0.01) (Bcl-2 expression (A scale): (62.54 ± 9.74) vs. (130.52 ± 9.86, F = 118.44, P < 0.01). Compared with PQ poisoning group, the protein expressions of LC3 and Bcl-2 were obviously increased in PU groups [LC3expression (A scale): (162.58 ±25.76) vs. (78.34 ± 10.71), F = 31.63, P < 0.01]; [Bcl-2 expression (A scale): (145.56 ±10.26) as. (62.54 ±9.74), F = 118.44, P < 0.01]. Conclusions: The endoplasmic reticulum stress - autophagy is activated in the lung cells of rats with acute PQ poisoning. UTI can adjust endoplasmic reticulum stress, increased the expression of Bcl-2 and enhance the proportion of Bcl-2/Bax to protect the lungs of rats from acute PQ poisoning.     

乌司他丁对脓毒症大鼠心脏组织基因表达的影响

Objective To observe the regulatory effect of ulinastatin (UTI)preconditioning on gene expression of heart tissue in septic rats by DNA microarrays.Methods Forty-five male Wistar rats were equally divided into control group, sepsis group and UTI group by means of random number table.Cecal ligation and puncture (CLP) was used to reproduce rat sepsis model.The control group only experienced a simulated operation without CLP.In UTI group the rats were treated with intramuscular injection of UTI 100 kU/kg 1 hour before CLP.In sepsis group and control group balanced electrolyte solution (5 ml/kg) was given.Gene expression spectrum was studied with RatRef-12 rat gene expression profile microarray to detect the changes in gene expression pattern of rat heart tissue after CLP.Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)＞2.0 or RA＜0.5 were identified as differential genes,and those highly correlated to sepsis and UTI groups were screened by means of related computer software to analyze their relationship.Results In 22 523 genes,418 differential genes were found in sepsis group compared with control group,accounting for 1.856%, and among them 200 genes showed up-regulation, with 84 known functional genes,and 43 of which only showed up-regulation in sepsis group,but normal in UTI group.Two hundred and eighteen genes showed down-regulation, with 74 known functional genes, 37 of which only showed down-regulation in sepsis group, but normal in UTI group.Two hundred and two differential genes were found in UTI group compared with control group, accounting for 0.897%, and among them 111 genes showed up-regulation, with 57 known functional genes, and 17 of which only showed up-regulation in UTI group, but normal in sepsis group.Ninety-one genes showed down-regulation, with 48 known functional genes, 18 of which only showed down-regulation in UTI group, but normal in sepsis group.Compared with the control group, in both UTI group and sepsis group, 41 of known functional genes showed up-regulation,and 37 showed down-regulation.Conclusion UTI preconditioning can ameliorate the damage to heart tissue in rat sepsis model, thus it has a protective effect on heart, and its mechanism may be attributable to regulatory effect of UTI on expression of stress reaction, cell signal transduction, energy metabolism,immune reaction and other related genes.     

二维斑点追踪技术评价舒张性心力衰竭患者左室心内膜和心外膜下心肌功能

目的 应用二维斑点追踪成像技术评价射血分数正常的舒张性心力衰竭(diastolic heart failure,DHF)患者左室心内、外膜下心肌功能.方法 临床确诊的DHF患者36例、收缩性心力衰竭(systolic heart failure,SHF)患者20例及正常对照组41例.二维超声心动图分别存储胸骨旁左室短轴基底水平、心尖水平连续3个心动周期的二维灰阶图像.使用Qlab 7.0工作站进行脱机分析,记录左室上述两短轴切面心内、外膜下心肌旋转角度.结果 ①所有受检者左室同一水平心内、外膜下心肌旋转运动呈相同方向运动,心尖水平呈逆时针方向旋转,基底水平呈顺时针方向旋转.②心尖水平及基底水平心内膜下心肌旋转角度均大于心外膜下心肌旋转角度.③与正常对照组相比,DHF及SHF患者心尖水平心内膜下心肌旋转角度减低;DHF患者心尖水平心外膜下心肌旋转角度与正常组比较未见明显减低,SHF组较正常组及DHF组明显减低.④DHF组基底水平心内、外膜下心肌旋转角度较正常对照组相应心肌层旋转角度值减低,但差异无统计学意义.SHF患者基底水平心内、外膜下心肌旋转角度显著减低.结论 SHF患者左室心内膜下心肌和心外膜下心肌旋转运动减低;DHF患者左室心尖水平心内膜下心肌旋转运动减弱,射血分数正常的DHF患者存在收缩功能异常.

Abstract：

Objective To observe the rotation of subendocardium and subepidium by two-dimensional speckle tracking imaging(2D-STI),and to evaluate its performance in diastolic heart failure patients(DHF)with a normal left ventricular ejection fraction. Methods Ninety-seven consecutive clinically stable patients were enrolled in this study [41 healthy controls,36 with diastolic heart failure,20 with systolic heart failure (SHF)]. High frame rate dynamic two-dimensional images were recorded at the left ventricular short-axis view,including basal, papillary muscle and apical planes. Subendocardial and subepicardial global rotation were measured using Q-lab 7.0 software offline. Results ① In all the subjects, the rotation of the subendocardium was obviously greater than that of subepicardium. ②As seen from the apex,left ventricular subendocardium and subepicardium performed a wringing motion with a clockwise rotation at the base and countclockwise rotation at the apex. ③In the apical plane, subendocardial rotation was significantly lower in both heart failure groups than in controls,and was depressed to a larger extent in SHF patients than in those with DHF. Subepicardial rotation was no significant difference between the DHF group and the control group, though it was significantly lower in patients with SHF. ④At the base, the rotation of subendocardium and subepicardium were not different between DHF and control groups, but it was significantly reduced in patients with SHF. Conclusions The subendocardial rotation is reduced, but subepicardial rotation is normal in DHF patients. On the other hand, in patients with SHF, subendocardial and subepicardial rotation are both reduced. The left ventricular systolic properties are impaired in DHF patients.     

Electro-acupuncture up-regulates the expression of stromal cell-derived factor-1α mRNA and its protein and promotes revascularization in the brain after focal cerebral ischemia and reperfusion

Objective To investigate the mechanism by which electro-acupuncture (EA) promotes revascularization in the brain after focal cerebral ischemia and reperfusion.Methods The Sprague-Dawley rat model of focal cerebral ischemia was made by filament occlusion. The rats were randomly divided into a control group, a model group, and an EA group. The model and EA groups were each divided into 5 subgroups receiving reperfusion 1, 3,7, 14 or 21 days after ischemia. EA was given at the bilateral Hegn point (LI 4) in the EA group. The expression of stromal cell-derived factor-1α(SDF-1α) mRNA was detected using a RT-PCR in the 3, 7 and 14 day subgroups.The immunohistochemical method was employed to detect the expression of SDF-1α protein. Results Compared with the control group, expression of SDF-1α protein increased significantly in the model and EA groups. Compared with the model group, the expression of SDF-1α mRNA increased significantly in the 3, 7 and 14 day subgroups.SDF-1α protein expression and microvessel count increased slightly but not significantly in the 1d subgroup, but the increases were significant in the 3, 7, 14 and 21 day subgroups.Conclusions EA may promote angiogenesis in an ischemic area of the cortex by increasing the expression of SDF-1αmRNA and its protein after focal cerebral ischemia and reperfusion.     

Electro-acupuncture up-regulates the expression of stromal cell-derived factor-1α mRNA and its protein and promotes revascularization in the brain after focal cerebral ischemia and reperfusion

Objective To investigate the mechanism by which electro-acupuncture (EA) promotes revascularization in the brain after focal cerebral ischemia and reperfusion.Methods The Sprague-Dawley rat model of focal cerebral ischemia was made by filament occlusion. The rats were randomly divided into a control group, a model group, and an EA group. The model and EA groups were each divided into 5 subgroups receiving reperfusion 1, 3,7, 14 or 21 days after ischemia. EA was given at the bilateral Hegn point (LI 4) in the EA group. The expression of stromal cell-derived factor-1α(SDF-1α) mRNA was detected using a RT-PCR in the 3, 7 and 14 day subgroups.The immunohistochemical method was employed to detect the expression of SDF-1α protein. Results Compared with the control group, expression of SDF-1α protein increased significantly in the model and EA groups. Compared with the model group, the expression of SDF-1α mRNA increased significantly in the 3, 7 and 14 day subgroups.SDF-1α protein expression and microvessel count increased slightly but not significantly in the 1d subgroup, but the increases were significant in the 3, 7, 14 and 21 day subgroups.Conclusions EA may promote angiogenesis in an ischemic area of the cortex by increasing the expression of SDF-1αmRNA and its protein after focal cerebral ischemia and reperfusion.