Black S C, Katz S, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Diabetes. 1989 Aug;38(8):969-74. doi: 10.2337/diab.38.8.969.
We studied the effect of omega-3 fatty acid (omega 3FA) treatment on plasma lipids and cardiomyopathy in the diabetic rat. The omega 3FA preparation used was Promega. Male Wistar rats (250-275 g) were rendered diabetic by streptozocin (STZ; 55 mg.kg-1). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to either a treated or untreated group. Promega was administered at a dose of 0.5 ml.kg-1.day-1 by oral gavage for 4 wk, after which the rats were decapitated, plasma collected, and isolated working heart performance studied. Promega treatment did not affect plasma glucose, triglyceride, or cholesterol concentrations of either the control or diabetic rats. Cardiac performance was assessed by measuring the left ventricular response to changing left atrial filling pressures (7.5-20 cm H2O). The treatment had no effect on peak left ventricular developed pressure (LVDP) or maximal rate of change of left ventricular pressure during systole (+dP/dtmax) or diastole (-dP/dtmax) in the nondiabetic control rats. LVDP and +/- dP/dt were significantly improved (P less than .05) in the treated diabetic rats compared with untreated diabetic rats, although cardiac performance did not improve to the nondiabetic level. Cardiac sarcoplasmic reticulum (SR) calcium transport activity was not affected by the treatment in the control rats but was significantly improved (P less than .05) in the treated diabetic rats. These data suggest that omega 3FA treatment partially blocks the development of experimental diabetic cardiomyopathy, possibly by affecting SR calcium transport activity.
我们研究了ω-3脂肪酸(ω-3FA)治疗对糖尿病大鼠血脂和心肌病的影响。所用的ω-3FA制剂为Promega。雄性Wistar大鼠(250 - 275克)通过链脲佐菌素(STZ;55毫克·千克⁻¹)诱导成糖尿病。非糖尿病对照大鼠仅接受赋形剂。在注射STZ或赋形剂两周后,将对照和糖尿病大鼠随机分为治疗组或未治疗组。通过口服灌胃以0.5毫升·千克⁻¹·天⁻¹的剂量给予Promega,持续4周,之后将大鼠断头,收集血浆,并研究离体工作心脏的性能。Promega治疗对对照或糖尿病大鼠的血糖、甘油三酯或胆固醇浓度均无影响。通过测量左心室对左心房充盈压变化(7.5 - 20厘米水柱)的反应来评估心脏性能。该治疗对非糖尿病对照大鼠的左心室峰值收缩压(LVDP)或收缩期(+dP/dtmax)和舒张期(-dP/dtmax)左心室压力的最大变化率没有影响。与未治疗的糖尿病大鼠相比,治疗后的糖尿病大鼠的LVDP和±dP/dt有显著改善(P < 0.05),尽管心脏性能未恢复到非糖尿病水平。心脏肌浆网(SR)钙转运活性在对照大鼠中不受治疗影响,但在治疗后的糖尿病大鼠中显著改善(P < 0.05)。这些数据表明,ω-3FA治疗可能通过影响SR钙转运活性,部分阻断实验性糖尿病心肌病的发展。