Ng T W K, Watts G F, Stuckey B G A, Ching H L, Chan D C F, Uchida Y, Sakai N, Yamashita S, Martins I J, Redgrave T G, Barrett P H R
School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth, Australia.
Clin Endocrinol (Oxf). 2005 Dec;63(6):650-6. doi: 10.1111/j.1365-2265.2005.02396.x.
We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus.
Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism.
Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements.
In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.
我们采用13C稳定同位素呼气试验以及检测血浆载脂蛋白（apo）B - 48和残粒样颗粒（RLP）-胆固醇，研究了普伐他汀对绝经后2型糖尿病女性乳糜微粒残粒分解代谢的影响。
19名绝经后2型糖尿病女性被随机分为两组，一组每天服用40mg普伐他汀，另一组不接受治疗，为期6周，随后有2周的洗脱期，之后两组交叉再进行6周的治疗。采用同位素比率质谱法和多室模型，根据呼出气体和血浆中13CO2的富集情况，测定乳糜微粒残粒样乳剂的分解代谢率（FCR）。还测量了血浆apo B - 48和RLP -胆固醇浓度，作为乳糜微粒残粒代谢的静态指标。
普伐他汀显著降低了血浆胆固醇浓度（5.9±0.3 vs. 4.8±0.2 mmol/l；P<0.001）、低密度脂蛋白（LDL）-胆固醇（3.5±0.2 vs. 2.6±0.2 mmol/l；P<0.001）、甘油三酯（2.1±0.3 vs. 1.7±0.2 mmol/l；P = 0.017）、非高密度脂蛋白（HDL）-胆固醇（4.4±0.3 vs. 3.3±0.2 mmol/l；P<0.001）、羊毛甾醇/总胆固醇比值（2.6±0.2 vs. 2.0±0.3，P = 0.035）、apo B - 100（1.1±0.1 vs. 0.8±0.1 g/l；P = 0.001）、apo B - 48（4.8±0.9 vs. 3.3±0.6 mg/l；P = 0.016）以及RLP -胆固醇（31.4±8.2 vs. 18.6±4.6 mg/dl；P = 0.024）。普伐他汀还与谷甾醇/总胆固醇比值升高有关（2.8±0.3 vs. 3.1±0.3，P = 0.029）。然而，通过呼气或血浆清除率测量评估，普伐他汀并未显著改变乳糜微粒残粒样乳剂的分解代谢。
在绝经后女性中，普伐他汀通过一种可能主要与抑制残粒产生有关的机制降低血浆残粒脂蛋白浓度，但这需要进一步评估。
