普罗布考对甲基胍诱导纤维化相关因子在HK-2细胞表达的影响

目的研究降脂药普罗布考对小分子尿毒素甲基胍诱导纤维化相关因子在人肾小管上皮细胞表达的影响。方法 HK-2细胞分3组培养,A组（正常对照,不加干预因素）;B组培养基中加入0.5mmol.L-1甲基胍;C组培养基中加入0.5mmol.L-1甲基胍和20μmol.L-1普罗布考。各组细胞培养48h后用免疫细胞化学、RT-PCR检测TGF-β1、CTGF和FN,并用流式细胞仪对以上因子作定量检测,以观察其在HK-2细胞中的表达。结果在甲基胍刺激后,细胞免疫化学染色,HK-2细胞质中着色,显示TGF-β1、CTGF和FN均有表达。正常对照组HK-2细胞质中无着色。测定结果显示甲基胍组TGF-β1、CTGF和FN显著高于正常对照组（P〈0.01）,加入普罗布考后,表达显著下降（P〈0.01）。结论甲基胍能促进纤维化相关因子在肾小管上皮细胞中表达;普罗布考能抑制甲基胍诱导纤维化相关因子在肾小管上皮细胞的表达。     

普罗布考对高密度脂蛋白胆固醇代谢的影响及其作用机制

普罗布考是一种调脂药 ,其在降脂同时显著降低了血浆HDL C含量却能抗动脉粥样硬化。高密度脂蛋白 胆固醇 (HDL C)在体内的代谢过程目前尚未清楚 ,有研究表明普罗布考通过促进胆固醇逆向转运途径而抗动脉粥样硬化。文章综述普罗布考对体内HDL C代谢的影响及其作用机制。     

普罗布考改善AMI患者PCI预后及炎症反应的临床研究

目的：研究使用普罗布考对急性心肌梗死（AMI）患者冠状动脉介入术（PCI）后预后及炎症反应的作用。方法：AMI患者82例,随机分为普罗布考组（41例）及对照组（41例）,两组患者均行冠状动脉造影及PCI治疗。普罗布考组在常规用药基础上加普罗布考500mg/次,每日2次。对照组应用辛伐他汀10mg每晚一次口服。记录所有患者住院期间及出院后30 d内心血管事件。并予以炎症相关生物标志物——肿瘤坏死因子（TNF-α）,CD40配体（CD40L）,P选择素（Ps）检测。结果：普罗布考组住院期间及出院后30 d累计发生心血管事件3例,与对照组相同（P〉0.05）。两组术前CD40L,Ps及TNF-α水平无统计学差异（P〉0.05）;出院后30 d CD40L,Ps及TNF-α各指标同术前比较均显著下降（P〈0.05）;普罗布考组出院后30d TNF-α,CD40L,Ps水平较与照组无明显差异（P〉0.05）。结论：普罗布考可减轻AMI行PCI治疗患者炎症反应,改善预后。     

普罗布考与阿托伐他汀联合用药对高脂饮食自发性高血压大鼠血脂的影响

目的评价普罗布考和阿托伐他汀联合用药的调脂作用。方法将92只雄性自发性高血压大鼠随机分为普通饲料+生理盐水组(C组)、高脂饲料+生理盐水组(M组)、高脂饲料+普罗布考组(P组)、高脂饲料+阿托伐他汀组(A组)和高脂饲料+阿托伐他汀+普罗布考组(P+A组),实验8周后处死。实验前及实验结束时均抽血查血脂,包括总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),以及肝功能,如谷丙转氨酶(GPT)和谷草转氨酶(GOT)。结果高脂饮食各组动物血清TC、LDL-C、HDL-C水平较实验前均明显升高(P<0.01),TG明显下降(P<0.01);各用药组动物(尤其是P+A组)TC、LDL-C均明显低于M组(P<0.01);P+A组血清HDL水平明显低于M组和A组(P<0.01),TG水平明显低于M组(P<0.01),并低于P组(P<0.05);A组TG水平亦明显低于M组(P<0.01)。高脂饮食各组动物血清GPT、GOT水平均较实验前明显升高(M组最高),且P+A组明显低于A组(均P<0.01)。结论高脂饮食可导致血脂紊乱及肝功能损害;普罗布考与阿托伐他汀联合用药可增强调脂作用,且较两者单独用药效果更佳;两者联合用药可减轻高脂饮食对肝功能的损害,并减轻阿托伐他汀的肝毒性。     

普罗布考的研究新进展及应用前景

普罗布考具有降低血脂、抗氧化、抗炎等作用,可以减少动脉粥样硬化的发生发展,防治经皮冠状动脉介入术后再狭窄,近年研究发现其在糖尿病等多种疾病中疗效显著。     

普罗布考和科素亚对兔血管成形术后生长因子的影响

目的：研究普罗布考和科素亚对兔血管成形术后再狭窄的预防作用及其对生长因子表达的影响。方法：雄性新西兰白兔40只,随机分为高胆固醇组、普罗布考组、科素亚组和联合用药组。1周后进行髂动脉球囊拉伤术,术后4周进行弹力纤维染色,用免疫组化检测血管胰岛素样生长因子-Ⅰ受体（insulin-like growth factor-Ⅰ receptor,IGF-IR）和内皮生长因子（vascular endothelial growth factor,VEGF）表达。结果：与高胆固醇组相比,普罗布考组、科素亚组和联合用药组管腔面积明显扩大（P〈0．01）,内膜面积明显减少（P〈0．05）,IGF-IR和VEGF表达明显减少（P〈0．01）,但3组间相比差异无统计学意义（P〉0．05）。结论：普罗布考和科素亚可以显著减轻兔髂动脉血管成形术后再狭窄的形成,抑制IGF—IR和VEGF的表达。联合用药与单独用药之间差异无统计学意义。     

固态自微乳提高普罗布考口服吸收

采用研磨法制备了平均粒径约27 nm普罗布考固态自微乳(1-SSME),差示扫描量热和X-射线衍射分析结果表明药物以非晶型状态存在于固态自微乳中.在0.1 mol/L盐酸和pH 6.8磷酸盐缓冲液中,1-SSME的1h溶出率分别为56％和66％.大鼠体内药动学研究表明,与1原药相比,口服1-SSME后的cmax和AUC显著提高,相对生物利用度为350％.     

Epithelial-to-Mesenchymal Transdifferentiation of Renal Tubular Epithelial Cell Mediated by Oxidative Stress and Intervention Effect of Probucol in Diabetic Nephropathy Rats

Objective: To elucidate the relationship of oxidative stress and specificity protein 1 (Sp1) in the process of epithelial-to-mesenchymal transdifferentiation (EMT) and also to investigate the molecular mechanism of protective effect of probucol on the pathogenesis of diabetic kidney disease (DKD). Methods: Thirty male Sprague–Dawley (SD) rats were randomly divided into control group, diabetic group, and diabetic group under probucol therapy (n = 10 per group). The biochemical indicators including 24-h urinary total protein (24-h UTP) excretion, blood glucose (BG), lipids [triglycerides (TGs), total cholesterol (TC)], serum creatinine (Scr), creatinine clearance rate (Ccr), kidney tissue malondialdehyde (MDA) level, and glutathione peroxidase (GSH-Px) activity were assessed in all groups. The renal pathological changes were evaluated by hematoxylin and eosin (HE) and Masson staining. The protein expression of Sp1, α-smooth muscle actin (α-SMA), and E-cadherin was also measured and analyzed by immunohistochemistry and Western blotting. Results: Compared with the control group, the BG, TC, Scr, 24-h UTP, and MDA level of renal tissue increased significantly and the Ccr reduced in the rats of diabetic group (all p < 0.01). The pathological scores and the expression of Sp1 and α-SMA in renal tissue were up-regulated (p < 0.01) and the expression of E-cadherin was down-regulated significantly in the diabetic animals (p < 0.01). In the diabetic animals treated with probucol, the renal injuries were alleviated (p < 0.01). Conclusions: Oxidative stress may play an important role in the EMT process of tubular epithelial cells. Probucol could ameliorate renal disease progression in this model of diabetic nephropathy, which might be due to an antioxidant action, down-regulation of Sp1 protein expression, and inhibition of renal tubular EMT.     

Both Atorvastatin and Probucol Can Down-regulate BMP-2 xpression Induced by Oxidized Low Density Lipoprotein in Human Umbilical Vein Cells

Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65,PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.