磷酸肌酸钠治疗充血性心力衰竭的疗效研究

目的：探讨磷酸肌酸钠治疗充血性心力衰竭的疗效。方法选取2011年4月—2014年4月信阳市中心医院收治的充血性心力衰竭患者100例,随机分为试验组与对照组,各50例。对照组患者予以常规药物治疗,试验组患者在对照组基础上加用磷酸肌酸钠治疗。观察两组患者临床疗效及治疗前后心功能指标。结果试验组患者总有效率为84%,高于对照组的62%,差异有统计学意义（ P <0.05）;治疗前两组患者左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）和左心室射血分数（LVEF）比较,差异无统计学意义（P>0.05）;治疗后试验组患者LVESD和LVEDD短于对照组,LVEF高于对照组,差异有统计学意义（ P<0.05）。结论磷酸肌酸钠治疗充血性心力衰竭的疗效显著,可改善患者心功能指标。     

Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity

Creatine is a molecule that supports energy metabolism in cells. It is carried across the plasma membrane by the creatine transporter. There has been recent interest in creatine for its neuroprotective effects in neurodegenerative diseases and its potential as a therapeutic agent. This study represents the first systematic investigation of the distribution of the creatine transporter in the human brain. We have used immunohistochemical techniques to map out its location and the intensity of staining. The transporter was found to be strongly expressed, especially in the large projection neurons of the brain and spinal cord. These include the pyramidal neurons in the cerebral cortex, Purkinje cells in the cerebellar cortex, and motor neurons of the somatic motor and visceromotor cranial nerve nuclei and the ventral horn of the spinal cord. Many other neurons in the brain also had some degree of creatine transporter immunoreactivity. By contrast, the medium spiny neurons of the striatum and the catecholaminergic neurons of the substantia nigra and locus coeruleus, which are implicated in neurodegenerative diseases, showed a very low to almost absent level of immunoreactivity for the transporter. We propose that the distribution may reflect the energy consumption by different cell types and that the extent of creatine transporter expression is proportional to the cell's energy requirements. Furthermore, the distribution indicates that supplemented creatine would be widely taken up by brain cells, although possibly less by those cells that degenerate in Huntington's and Parkinson's diseases. J. Comp. Neurol. 523:699–725, 2015. © 2014 Wiley Periodicals, Inc.     

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized,double‐blind,placebo‐controlled crossover trial

Introduction: It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. Methods: In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double‐blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health‐related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Results: Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Conclusions: Twelve weeks of creatine supplementation in JDM patients were well‐tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. Muscle Nerve 53 : 58–66, 2016     

磷酸肌酸对心肌肥厚及心力衰竭大鼠的治疗作用

目的 :探讨磷酸肌酸对压力负荷性心力衰竭的治疗机制。方法 :腹主动脉次全结扎 SD大鼠 55只 ,分 5组给予不同干预 8周 ,观察磷酸肌酸疗效及寻找更好的用药方案。结果 :磷酸肌酸可以减低高血压性心力衰竭大鼠的失代偿性心衰的发生率和死亡率 ,失代偿性心衰组大鼠心肌细胞内 ATP含量明显减低 ;血管紧张素转换酶抑制剂 （A-CEI）雷米普利 +磷酸肌酸比单独使用磷酸肌酸更好地改善高血压性心功能障碍 （代偿性 ）大鼠的血流动力学 ,可能与血压的下降及心肌胶原沉积的改善有关 ,磷酸肌酸及雷米普利治疗对代偿性高血压性心力衰竭大鼠心肌细胞内ATP含量影响不明显。结论 :对于失代偿性高血压性心力衰竭 ,磷酸肌酸可以减低其发生率和死亡率。对于代偿性高血压心力衰竭 ACEI+磷酸肌酸方案效果更佳     

磷酸肌酸对阿霉素致大鼠心肌损伤的保护作用及其抗细胞凋亡的实验研究

目的通过建立大鼠阿霉素心肌损伤模型,观察磷酸肌酸对阿霉素心肌损伤的保护作用,并研究磷酸肌酸抑制心肌细胞凋亡的机制。方法采用随机分组的方法将40只SD大鼠分为4组。（1）对照组：腹腔注射生理盐水每日一次;（2）阿霉素组：隔日一次腹腔注射阿霉素建立阿霉素心肌损伤模型。（3）阿霉素＋磷酸肌酸钠组（小剂量）：隔日一次腹腔注射磷酸肌酸钠（200mg/kg）,30min后注射阿霉素。（4）阿霉素＋磷酸肌酸钠组（大剂量）：隔日1次腹腔注射磷酸肌酸钠（300mg/kg）,30min后注射阿霉素。用药结束后测定各组大鼠血清、心肌组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、过氧化氢酶（CAT）活性,血清中肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）含量变化。取心肌组织HE染色,观察大鼠心肌病理形态学变化。免疫组织化学染色方法检测各组心肌组织中BAX、BCL-2蛋白表达情况。结果两组加入磷酸肌酸钠大鼠脂质过氧化产物MDA含量减少,心肌抗氧化酶SOD及CAT活性增加,血清中CK、CK-MB含量减少,与阿霉素组比较有统计学意义（P〈0.05）。免疫组化结果显示,磷酸肌酸钠组大鼠心肌促凋亡蛋白BAX表达减弱,抗凋亡蛋白BCL-2表达增强,且与阿霉素组比较有意义（P〈0.05）。给予不同剂量磷酸肌酸钠的两组大鼠,各项检测指标未见差异（P〈0.05）。结论磷酸肌酸通过增强抗氧化酶系统的功能,降低阿霉素引起的氧化应激损伤,抑制自由基引起的心肌细胞凋亡,起到保护心脏功能的作用。     

磷酸肌酸钠预给药对大鼠局灶性脑缺血再灌注损伤的影响

目的:观察不同浓度磷酸肌酸钠预给药对大鼠脑缺血再灌注损伤(I/R)模型脑梗死体积的影响。方法:模型建立采用大脑中动脉线栓法。50只SD大鼠随机分为假手术组(Sham组),I/R组及低、中、高剂量磷酸肌酸钠预给药组(即L、M、H组),每组10只。再灌注末,测血清超氧化物歧化酶(SOD)、丙二醛(MDA)水平,脑组织中Na+-K+-ATP酶及髓过氧化物酶(MPO)活性。实验结束对脑组织进行HE、TTC染色,观察脑组织损伤情况。结果:再灌注24h末,各组间血清SOD、MDA及脑组织中MPO、Na+-K+-ATP酶活性比较差异有统计学意义(P<0.05);Bederson神经功能缺损评分显示Sham组无损伤,其余各组均出现不同程度的神经损伤。脑梗死体积百分比比较,Sham组脑组织无梗死,I/R组脑梗死体积百分比较L、M、H组明显增大,L组大于M组、H组;M组脑梗死体积大于H组,差异均有统计学意义(P<0.05)。结论:低、中、高浓度磷酸肌酸钠预给药均可有效地减少局灶性脑缺血再灌注损伤后大鼠脑梗死体积,减轻脑缺血再灌注后的损伤。     

Astrocyte volume regulation and ATP and phosphocreatine concentrations after exposure to salicylate,ammonium, and fatty acids

Cellular volume regulation following swelling in hypo-osmotic phosphate-buffered saline (PBS) and ATP and phosphocreatine concentrations of cells incubated in iso-osmotic or hypo-osmotic PBS were measured in primary cultured rat cerebral astrocytes exposed for 30 min to NH₄Cl, salicylate, hexanoate, octanoate, and/or dodecanoate. These compounds have been implicated in the pathogenesis of cerebral edema in Reye's Syndrome. NH₄Cl (0.10–10 raM) had no effect on astrocyte volume regulation or ATP concentration. Salicylate significantly reduced ATP concentrations at 3.0 mM and 10 mM but had no effect on volume regulation. Hexanoate (10 mM and 30 mM) decreased astrocyte ATP content by over 80% while octanoate (10 mM) reduced ATP content by more than 50%. Concentrations of these fatty acids at or below 3.0 mM had no effect on ATP content. Volume regulation was inhibited by 3.0 mM hexanoate and 3.0 mM octanoate but not lower concentrations. Dodecanoate (0.1–3.0 mM) decreased cellular ATP content by 33–51% in iso-osmotic PBS solutions. Phosphocreatine content was reduced by exposure to salicylate or octanoate at concentrations which had no effect on ATP content. These results indicate that astrocyte energy metabolism and volume regulation may be compromised by agents associated with cerebral edema in Reye's Syndrome. Analysis of the dose-dependence of these effects suggests that inhibition of astrocyte energy metabolism is not sufficient to affect volume regulation.     

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised ³¹P and ¹H magnetic resonance spectroscopy. Methods. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months. Results. In ³¹P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In ¹H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls ¹H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (–14 % and –23 %) and N-acetylaspartate:choline (–21 % and –17 %) ratios after 2 weeks and 8 months of diabetes, respectively. Conclusion/interpretation. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in N-acetylaspartate levels in the brain of STZ-diabetic rats were shown by ¹H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes. [Diabetologia (2001) 44: 346–353] Received: 3 August 2000 and in revised form: 17 October 2000     

Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart

Heart failure patients have abnormal cardiac high energy phosphate metabolism, the explanation for which is unknown. Patients with heart failure also have elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are associated with increased cardiac mitochondrial uncoupling proteins (UCPs), which, in turn, are associated with decreased mitochondrial respiratory coupling and low cardiac efficiency. Here, we determined whether increased mitochondrial UCP levels contribute to decreased energetics in the failing heart by measuring UCPs and respiration in mitochondria isolated from the viable myocardium of chronically infarcted rat hearts and measuring efficiency (hydraulic work/O₂ consumption) in the isolated, working rat heart. Ten weeks after infarction, cardiac levels of UCP3 were increased by 53% in infarcted, failing hearts that had ejection fractions less than 45%. Cardiac UCP3 levels correlated positively with non-fasting plasma FFAs (r = 0.81; p < 0.01). Mitochondria from failing hearts were less coupled than those from control hearts, as demonstrated by the lower ADP/O ratio of 1.9 ± 0.1 compared with 2.5 ± 0.2 in controls (p < 0.05). The decreased ADP/O ratio was reflected in an efficiency of 14 ± 2% in the failing hearts when perfused with 1 mM palmitate, compared with 20 ± 1% in controls (p < 0.05). We conclude that failing hearts have increased UCP3 levels that are associated with high circulating FFA concentrations, mitochondrial uncoupling, and decreased cardiac efficiency. Thus, respiratory uncoupling may underlie the abnormal energetics and low efficiency in the failing heart, although whether this is maladaptive or adaptive would require direct investigation.