目的 采用高效液相色谱-质谱联用法（HPLC-MS/MS）研究普罗布考片的人体药物代谢动力学变化规律。 方法 2010年10月－11月，24例健康男性受试者单次口服普罗布考片0.5 g，采用HPLC-MS/MS法测定给药后不同时间点血浆中普罗布考的经时血药浓度，采用DAS 2.0软件进行药动学参数计算。 结果 受试者单次口服普罗布考片，达峰时间为（11.50 ± 6.66）h，峰浓度为（2 894.72 ± 1 320.53）ng/mL，药-时曲线下面积（AUC）0-t为（238 876.96 ± 131 873.67） ng/mL· h，AUC0-∞为（259 989.08 ± 146 112.88）ng/mL· h，半衰期为（278.52 ± 164.72） h。结论 普罗布考片体内过程符合二室模型，单次口服具有较好的安全性。
目的:探讨普罗布考对动脉粥样硬化性脑梗死并高脂血症患者血脂及预后的影响。方法:将87例脑梗死并高脂血症患者随机分为两组,治疗组44例,对照组43例,两组除按动脉粥样硬化性脑梗死常规治疗外,停用一切降脂药物。治疗组给予普罗布考500mg bid/d。疗程为6个月。随访一年观察两组患者治疗后血脂水平及脑血管事件发生情况。结果:治疗组患者治疗前、后总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)间差异均有显著性意义(Plt;0.05)。两组患者治疗后各项血脂指标间差异均有显著性意义(Plt;0.05)。随访一年,显示治疗组患者心脑血管事件14次,对照组19次(Plt;0.05)。结论:普罗布考降脂疗效可靠、副作用轻微,降低心脑血管事件发生。可作为动脉粥样硬化性脑梗死并高脂血症患者的一、二级预防药物。
ObjectiveTo observe the expression of probucol on high glucose-induced specificity protein 1(SP1), kelchlike ECH associated protein1 (Keap1), NF-E2-related factor 2 (Nrf2) and glutamate-cysteine ligase catalytic (GCLC) in the cultured human müller cells and preliminary study the antioxidation of the probucol on müller cells.MethodsPrimary cultured human müller cells were randomly divided into four groups: normoglycaemia group (5.5 mmol/L glucose), normoglycaemia with probucol group (5.5 mmol/L glucose+100 μmol/L probucol), hyperglycemia group (25.0 mmol/L glucose), hyperglycemia with probucol group (25.0 mmol/L glucose + 100 μmol/L probucol). Immunofluorescence staining was used to assess distribution of SP1, Keap1, Nrf2, GCLC in human Müller cells. SP1, Keap1, Nrf2 and GCLC messenger RNA (mRNA) expression was evaluated by quantitative real-time RT-PCR (qRT-PCR). Independent sample t test was used to compare the data between the two groups.ResultsAll müller cells expressed glutamine synthetase (＞95%), which confirmed the cultured cells in vitro were the purification of generations of müller cells. The expressions of SP1, Keap1, Nrf2, and GCLC protein were positive in human müller cells. qRT-PCR indicated that SP1 (t=28.30, P＜0.000), Keap1 (t=5.369, P=0.006), and Nrf2 (t=10.59, P=0.001) mRNA in the hyperglycemia group increased obviously compared with the normoglycaemia group; GCLC (t=4.633, P=0.010) mRNA in the hyperglycemia group decreased significantly compared with the normoglycaemia group. However, SP1 (t=12.60, P=0.000) and Keap1 (t=4.076, P=0.015) in the hyperglycemia with probucol group decreased significantly compared with the hyperglycemia group; Nrf2 (t=12.90, P=0.000) and GCLC (t=15.96, P＜0.000) mRNA in the hyperglycemia with probucol group increased obviously compared with with the hyperglycemia group.ConclusionProbucol plays an antioxidant role by inhibiting the expression of SP1, Keap1 and up-regulating the expression of Nrf2, GCLC in müller cells induced by high glucose.