Ueno Y, Koike H, Nishio S
Toray Industries, Inc., Basic Research Laboratories, Kanagawa, Japan.
J Cardiovasc Pharmacol. 1995 Oct;26(4):603-7. doi: 10.1097/00005344-199510000-00015.
We examined whether beraprost sodium (beraprost), a stable prostacyclin analogue, prevented cardiomyopathy in diabetic rats in vivo. Diabetes was induced by a bolus injection of streptozotocin in rat-tail vein. Four weeks after the induction of diabetes, the animals were treated with beraprost (30 micrograms/kg/day, p.o.) for 4 weeks until they were used for the measurement of hemodynamics, electrocardiogram (ECG), and plasma creatine phosphokinase (CK) activity. Nontreated diabetic rats have lower mean blood pressure, heart rate, left ventricular systolic pressure, and peak positive dP/dt at basal levels compared to age-matched normal rats. All of these changes were not improved in beraprost-treated rats. The left ventricular end-diastolic pressure and ST/R ratio in the ECG were significantly increased in diabetic rats. These parameters were significantly improved by beraprost compared with nontreated diabetic rats. Additionally, beraprost significantly suppressed the elevation of plasma CK activity as compared with that in non-treated diabetic rats. Changes in peak positive dP/dt in response to isoproterenol were attenuated in nontreated diabetic rats as compared with age-matched normal rats and beraprost-treated diabetic rats. These results suggest that beraprost is capable of preventing diabetic cardiomyopathy without affecting hyperglycemic condition.
我们研究了稳定的前列环素类似物贝拉前列腺素钠（beraprost）在体内是否能预防糖尿病大鼠的心肌病。通过在大鼠尾静脉大剂量注射链脲佐菌素诱导糖尿病。糖尿病诱导四周后，对动物用贝拉前列腺素（30微克/千克/天，口服）治疗4周，直至用于测量血流动力学、心电图（ECG）和血浆肌酸磷酸激酶（CK）活性。与年龄匹配的正常大鼠相比，未治疗的糖尿病大鼠在基础水平时平均血压、心率、左心室收缩压和峰值正dP/dt较低。在贝拉前列腺素治疗的大鼠中，所有这些变化均未得到改善。糖尿病大鼠心电图中的左心室舒张末期压力和ST/R比值显著升高。与未治疗的糖尿病大鼠相比，贝拉前列腺素使这些参数得到显著改善。此外，与未治疗的糖尿病大鼠相比，贝拉前列腺素显著抑制了血浆CK活性的升高。与年龄匹配的正常大鼠和贝拉前列腺素治疗的糖尿病大鼠相比，未治疗的糖尿病大鼠对异丙肾上腺素反应时峰值正dP/dt的变化减弱。这些结果表明，贝拉前列腺素能够预防糖尿病心肌病，而不影响高血糖状况。
