Nash V J, Johnston T P, Palmer W K
School of Kinesiology, University of Illinois at Chicago 60608, USA.
Pharmacotherapy. 1996 Jan-Feb;16(1):10-5.
We attempted to determine the mechanism(s) of poloxamer (P)-407-induced hyperlipidemia in rats by administering a lipid-lowering drug with a known mechanism of action. Five weight-matched animals were assigned to each of four treatment groups. Two groups received P-407 300 mg/ml and two received saline 1 ml. One of the P-407 and one of the saline groups were administered nicotinic acid 100 mg/kg by intraperitoneal injection at 6-96 hours after blood sampling. Blood samples were collected at 7 points from time zero to 120 hours and analyzed for triglyceride and cholesterol concentrations. The detergent produces hypertriglyceridemia (HTG) increasing from 53.4 +/- 7.0 mg/dl (time zero) to 4026.9 +/- 42.1 mg/dl by 24 hours. The HTG response was significantly attenuated by nicotinic acid (at t = 24 hrs). This, however, was followed by an average triglyceride concentration increase of 2.8-fold from 72 to 120 hours. The detergent produces a dramatic hypercholesterolemia (HCHO), increasing cholesterol from 47.5 +/- 1.8 mg/dl to 468.5 +/- 27.9 mg/dl by 48 hours. The HCHO was significantly affected by nicotinic acid administration during the accumulation phase. Nicotinic acid reduced cholesterol concentration from 364.4 +/- 16.1 mg/dl to 276.8 +/- 16.4 mg/dl at 24 hours (p < 0.05). It is a potent antilipolytic agent, limiting the free fatty acids available for the synthesis of triglyceride and cholesterol. These data suggest that P-407 may act by stimulating the release of free fatty acids from the adipocyte for at least 24 hours after injection.
我们试图通过给予一种作用机制已知的降脂药物来确定泊洛沙姆（P）-407诱导大鼠高脂血症的机制。将五只体重匹配的动物分配到四个治疗组中的每组。两组接受300mg/ml的P-407，两组接受1ml生理盐水。在采血后6至96小时，P-407组中的一组和生理盐水组中的一组通过腹腔注射给予100mg/kg烟酸。在从0小时到120小时的7个时间点采集血样，并分析甘油三酯和胆固醇浓度。该去污剂产生高甘油三酯血症（HTG），从53.4±7.0mg/dl（0小时）增加到24小时时的4026.9±42.1mg/dl。烟酸显著减轻了HTG反应（在24小时时）。然而，随后甘油三酯浓度在72至120小时内平均增加了2.8倍。该去污剂产生显著的高胆固醇血症（HCHO），胆固醇在48小时内从47.5±1.8mg/dl增加到468.5±27.9mg/dl。在积累阶段，烟酸给药对HCHO有显著影响。烟酸在24小时时将胆固醇浓度从364.4±16.1mg/dl降低到276.8±16.4mg/dl（p<0.05）。它是一种有效的抗脂解剂，限制了可用于合成甘油三酯和胆固醇的游离脂肪酸。这些数据表明，P-407可能通过在注射后至少24小时刺激脂肪细胞释放游离脂肪酸而起作用。
