Ulicná O, Cízová M, Kolesár P, Volkovová K, Cibulová L, Cársky J, Ondrejka P
Farmakobiochemické laboratórium III. internej kliniky Lekárskej fakulty Univerzity Komenského v Bratislave, Slovakia.
Bratisl Lek Listy. 1997 Dec;98(12):687-94.
Diabetes mellitus represents an intense metabolic strain for the liver. Inhibitors of angiotensin-converting enzymes (ACEI) are drugs of choice in the therapy of hypertension in coincidence with diabetes mellitus. The effect of ACEI is complex. The attention is drawn to the study of metabolic effects of ACEI.
The aim of the study was to investigate whether the administration of ramipril affects the levels of glycated hemoglobin and fructoseamine in the blood of rats with insulin-dependent diabetes mellitus (IDDM), and whether bioenergetics of mitochondria in the liver undergo changes.
In our experiments, we used rats of the Wistar strain. The control group was composed of healthy animals. The experimental groups were formed by rats with IDDM evoked by streptozotocine (45 mg/kg) and rats with IDDM + ramipril (10 mg/KG). Both, insulin MONO-ID in the doses of 6 U/kg administered subcutaneously, and water solution of ramipril administered by gastric probe were applied for the period of 8 weeks. We have assessed blood levels of glucose, glycated hemoglobin, fructoseamine and the concentration of cholesterol and triacylglycerols have been assessed also in the liver. Oxidative phosphorylation in mitochondria of the liver were measured polarographically.
In the group with IDDM + ramipril, the glycated haemoglobin (M 6.85 CI 5.7-7.0%) and fructoseamine (M 1.45 CI 1.2-1.6 mmol/l) have significantly dropped in comparison with the group with IDDM glycated haemoglobin (M 8.8 7.7-10.7%) and fructoseamine (M 2.04 CI 1.69-2.4 mmol/l). Ramipril did not affect the concentration of cholesterol and triacylglycerols in the blood and liver in rats with IDDM. Ramipril has positively affected oxidative phosphorylation in mitochondria of the liver in coincidence with IDDM. The group with IDDM + ramipril has yielded an increase in the velocity of oxygen consumption in coincidence with stimulated breathing with ADP, the state 3 (M 107.97 CI 96.78-134.51 n AtO/mg of proteins/min.) and phosphorylation velocity (M 232.67 CI 209.38-284.97 nmolATP/protein/min) in contrast to the group with IDDM: the state 3 (M 76.71 CI 66.81-85.99 nAtO/mg of proteins/min and the velocity of phosphorylation (M 161.84 CI 143.55-189.99 nmol ATP/mg of proteins/min) in coincidence with substrate glutamate. A similar trend is present also in coincidence with FAD succinate substrate.
After the administration of ramipril to rats with IDDM, the indicators have improved, and they express the rate of compensation of diabetes mellitus. An increased capacity of the respiratory chain and an increased origin of energy in mitochondria in the livers of rats with IDDM after administration of ramipril indicates an improvement in the metabolic capacity of the liver. (Tab. 4. Ref. 47.)
糖尿病对肝脏构成强烈的代谢负担。血管紧张素转换酶抑制剂（ACEI）是合并糖尿病的高血压治疗的首选药物。ACEI的作用复杂。人们开始关注对ACEI代谢作用的研究。
本研究旨在探讨雷米普利的给药是否会影响胰岛素依赖型糖尿病（IDDM）大鼠血液中糖化血红蛋白和果糖胺的水平，以及肝脏线粒体的生物能量学是否会发生变化。
在我们的实验中，我们使用了Wistar品系的大鼠。对照组由健康动物组成。实验组由链脲佐菌素（45mg/kg）诱发的IDDM大鼠和IDDM+雷米普利（10mg/KG）大鼠组成。皮下注射剂量为6U/kg的胰岛素MONO-ID和通过胃探针给予的雷米普利水溶液，持续8周。我们评估了血液中的葡萄糖、糖化血红蛋白、果糖胺水平，并评估了肝脏中胆固醇和三酰甘油的浓度。用极谱法测量肝脏线粒体中的氧化磷酸化。
与IDDM组糖化血红蛋白（M 8.8 7.7 - 10.7%）和果糖胺（M 2.04 CI 1.69 - 2.4 mmol/l）相比，IDDM + 雷米普利组的糖化血红蛋白（M 6.85 CI 5.7 - 7.0%）和果糖胺（M 1.45 CI 1.2 - 1.6 mmol/l）显著下降。雷米普利不影响IDDM大鼠血液和肝脏中胆固醇和三酰甘油的浓度。雷米普利对IDDM大鼠肝脏线粒体中的氧化磷酸化有积极影响。与IDDM组相比，IDDM + 雷米普利组在ADP刺激呼吸时氧消耗速度增加，即状态3（M 107.97 CI 96.78 - 134.51 n AtO/mg蛋白质/分钟）和磷酸化速度（M 232.67 CI 209.38 - 284.97 nmolATP/蛋白质/分钟），与底物谷氨酸一致。与FAD琥珀酸底物一致时也存在类似趋势。
对IDDM大鼠给予雷米普利后，各项指标有所改善，这些指标反映了糖尿病的代偿率。雷米普利给药后，IDDM大鼠肝脏中呼吸链能力增强，线粒体能量产生增加，表明肝脏代谢能力有所改善。（表4。参考文献47。）
