匹伐他汀对冠心病合并非酒精性脂肪肝患者肝功能的影响

目的:观察匹伐他汀对肝功能正常冠心病(CHD)合并非酒精性脂肪肝(NAFLD)患者肝功能的影响。方法:选择我院CHD合并NAFLD且肝功能正常的患者205例为CHD+NAFLD组,根据NAFLD严重程度患者被分为轻度组87例、中度组64例、重度组54例,另选择同期在我院就诊的单纯CHD患者70例(CHD组)作为对照。四组均在常规治疗的基础上给予匹伐他汀治疗,治疗15d。观察四组治疗前后血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转移酶(γ-GT)水平和严重肝功能损害发生率。结果:治疗后CHD组、CHD+NAFLD轻、中、重度组血清ALT、AST、γ-GT水平均显著升高(P均=0.001),且四组治疗后ALT[(45.89±11.36)U/L比(46.92±12.67)U/L比(46.35±11.95)U/L比(47.32±14.06)U/L]、AST[(46.32±12.13)U/L比(48.54±13.49)U/L比(47.63±12.57)U/L比(48.66±13.54)U/L]、γ-GT[(58.49±14.86)U/L比(57.62±11.38)U/L比(57.92±10.51)U/L比(58.52±13.8)U/L]水平及严重肝功能损害发生率(2.90%比3.57%比1.61%比3.92%)相比较差异均无统计学意义(P均>0.05)。结论:与单纯CHD患者比较,匹伐他汀用于肝功能正常CHD联合NAFLD患者未增加肝功能损害,具有良好的临床安全性。     

心脑清软胶囊联合匹伐他汀治疗高脂血症的临床研究

目的探讨心脑清软胶囊联合匹伐他汀治疗高脂血症的临床疗效。方法选取2017年7月—2018年7月在河北省第七人民医院进行治疗的88例高脂血症患者,根据住院号的奇偶数分为对照组和治疗组,每组各44例。对照组饭后口服匹伐他汀钙片,1片/次,1次/d。治疗组在对照组治疗基础上饭后口服心脑清软胶囊,2粒/次,3次/d。两组均治疗8周后进行效果比较。观察两组的临床疗效,比较两组治疗前后血脂指标、肥胖指标、血清学指标和氧化应激指标的变化情况。结果治疗后,对照组和治疗组的总有效率分别是81.82%、93.18%,两组比较差异具有统计学意义(P0.05)。治疗后,两组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均较治疗前显著降低,而高密度脂蛋白胆固醇(HDL-C)水平均增高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组TC、TG、LDL-C水平显著低于对照组,而HDL-C水平高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组体质量、肥胖度、体质量指数、体脂率都明显下降,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组这些肥胖指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组超敏C反应蛋白(hs-CRP)、肿瘤坏死因素-α(TFN-α)、干扰素-γ(IFN-γ)、嗜酸粒细胞阳离子蛋白(ECP)、总氧化态(TOS)水平均较治疗前显著下降,而总抗氧化态(TAS)和对氧磷酶-1(PON1)表达水平均增高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组hs-CRP、TFN-α、IFN-γ、ECP、TOS水平低于对照组,而TAS和PON1表达水平均高于对照组,两组比较差异具有统计学意义(P0.05)。结论心脑清软胶囊联合匹伐他汀治疗高脂血症具有较好的临床疗效,可有效降低血脂水平和肥胖指标,改善机体炎症反应,改善机体氧化应激状态,具有一定的临床推广应用价值。     

Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in Alzheimer’s disease

Abstract

Objectives: To examine and compare the pleiotropic effects on oxidative stress and metabolic signaling pathways of atorvastatin and pitavastatin in mouse model of Alzheimer’s disease (AD).

Methods: We gave the transgenic (Tg) mice either atorvastatin or pitavastatin from 5–20 months (M) of age, and performed immunohistological analysis [4-hydroxy-2-nonenal (4-HNE)-positive, advanced glycation end products (AGEs), low-density lipoprotein receptor (LDL-R)-positive neurons, apolipoprotein E (ApoE)-positive senile plaque (SP), and insulin receptor (IR)-positive endothelium], and biochemistry analysis (adiponectin and leptin).

Results: The numbers of 4-HNE- and AGE-positive neurons and the sum of ApoE-positive SP size progressively increased with age in amyloid precursor protein (APP)-Tg mice, while the amount of IR-positive endothelium and the number of LDL-R-positive neurons decreased. Adiponectin and leptin serum levels were lower in APP-Tg mice than in non-Tg mice. Treatment with statins reduced the number of AGE-positive neurons from as early as 10 M, preserved the numbers of 4-HNE- and LDL-R-positive neurons and the amount of IR-positive endothelium at 15 M, and reduced the sum of ApoE-positive SP size and adiponectin serum level at 20 M.

Discussion: Atorvastatin and pitavastatin reduced the level of oxidative stress, as revealed by the presence of 4-HNE and AGE, in AD mouse brains, and that treatment with statins improves insulin signaling and LDL-R/ApoE systems. The beneficial effects of these statins may be associated with direct pleiotropic effects on AD mouse brains, indirect effects through improving the serum adiponectin/leptin balance, or both.     

LC–MS/MS assay for pitavastatin in human plasma and subsequent application to a clinical study in healthy Chinese volunteers

A rapid, selective and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the determination of pitavastatin in human plasma. Following a liquid–liquid extraction, both the analytes and internal standard telmisartan were separated on a Luna C₁₈ column with a mobile phase consisted of acetonitrile–methanol–1% formic acid in water (50:25:25, v/v/v). Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring (MRM) of the transitions at m/z 421.9 → 290.1 for pitavastatin and m/z 515.2 → 276.2 for the IS. The assay for pitavastatin showed good linearity (r ≥ 0.99) over the ranges 0.2–400 ng/ml, with a lower limit of quantitation of 0.2 ng/ml. Accuracy and precision for the assay were determined by calculating the intra- and inter-batch variation of quality control (QC) samples at three concentration levels, with relative standard deviations (RSD) of less than 15% for both analytes. The mean extraction recovery of pitavastatin and IS were both above 70%. Matrix effect hasn't been found in this method. The method has been successfully applied to a clinic pharmacokinetic study of pitavastatin administered.     

Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus

The aim of this study was to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Seventy-five hyperlipidemic patients with and without type 2 diabetes were enrolled to receive pitavastatin 2 mg daily. Cell adhesion molecules (sCD40L, sP-selectin, sE-selectin, and sL-selectin), chemokines (MCP-1 and RANTES) and adiponectin were measured at baseline and after 3 and 6 months of pitavastatin treatment. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the LDL-cholesterol (LDL-C) decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with type 2 diabetes exhibited a significant increase in adiponectin levels after pitavastatin treatment (before vs. 3 months, 6 months, 2.81 ± 0.95 vs. 3.84 ± 0.84 μg/ml (p < 0.01), 4.61 ± 1.15 μg/ml (p < 0.001)). Furthermore, hyperlipidemic diabetics exhibited significant decreases in sE-selectin and sL-selectin levels after 6 months of pitavastatin treatment (sE-selectin, before vs. 6 months, 74 ± 21 vs. 51 ± 10 ng/ml, p < 0.05; sL-selectin, before vs. 6 months, 896 ± 141 vs. 814 ± 129 ng/ml, p < 0.05). In addition, adiponectin showed significant correlation with sE-selectin and sL-selectin in diabetic hyperlipidemia. However, MCP-1, RANTES and sCD40L did not exhibit any differences before or after pitavastatin administration. These results suggest that pitavastatin possesses an adiponectin-dependent anti-atherosclerotic effect in hyperlipidemic patients with type 2 diabetes in addition to its lowering effects on total cholesterol and LDL-C.     

匹伐他汀钙及其中间体非对映异构体的合成

目的：为控制匹伐他汀钙的质量,合成匹伐他汀钙及其中间体非对映异构体中的C-5位差向异构体。方法：以（3R,5S,6E）-7-[2-环丙基-4-(4-氟苯基)-3-喹啉基]-3,5-二羟基-3,5-O-亚异丙基庚-6-烯酸叔丁酯（2）为原料经脱缩酮、氧化、反立体选择性还原得（3R,5R,6E）-7-[2-环丙基-4-(4-氟苯基)-3-喹啉基]-3,5-二羟基-6-庚烯酸叔丁酯（5）。5水解成盐得（+）-双-[（3R,5R,6E）-7-[2-环丙基-4-（4-氟苯基）-3-喹啉基]-3,5-二羟基-6-烯庚酸]单钙盐（1）。5与2,2-二甲氧基丙烷形成缩酮得化合物（3R,5R,6E）-7-[2-环丙基-4-（4-氟苯基）-3-喹啉基]-3,5-二羟基-3,5-O-亚异丙基-6-庚烯酸叔丁酯（4）。结果与结论：合成了匹伐他汀钙及其中间体的C-5位差向异构体,并经核磁共振氢谱、碳谱、质谱和比旋光度等确证结构,3个目标化合物5、1和4的总收率分别为70%、68%和56%（以2计）,纯度经HPLC检测均在97.5%以上,可以作为匹伐他汀钙原料药质量控制的对照品。     

匹伐他汀抑制实验性肺纤维化大鼠MMP-9和TIMP-1表达

目的探讨匹伐他汀对博来霉素诱导的大鼠肺纤维化模型中基质金属蛋白酶（MMP）-9及其抑制剂（TIMP）-1表达的影响。方法54只健康雄性SD大鼠随机分为阴性对照组（生理盐水）、模型组（5mg／kg博莱霉素）以及博莱霉素＋匹伐他汀组（5mg／kg）。分别于第2、4、6周获取6只大鼠肺组织及肺泡灌洗液（BALF）,Western blot和ELISA检测其MMP-9和TIMP-1水平的变化。结果对照组中MMP-9和PTIMP-1水平表达低,模型组中两者含量显著增高。5mg／垤匹伐他汀处理后,两者水平显著降低（P〈O05）。结论匹伐他汀能降低肺纤维化模型小鼠肺组织MMP-9和TIMP-1水平．可能是其抗肺纤维化的重要机制之一。     

不同种类他汀药物对慢性硬膜下血肿治疗的临床效果

目的探讨不同种类他汀药物对慢性硬膜下血肿治疗的临床效果。方法选择2015年12月～2017年12月本院收治的慢性硬膜下血肿患者120例,按照使用他汀类药物不同分为三组,均为40例。所有患者均行对症支持处理,A组使用辛伐他汀(40 mg/d,晚间顿服),B组使用匹伐他汀(口服,每次1 mg,每天1次),C组使用阿托伐他汀(40 mg/d),比较各组患者的临床治疗效果,比较各组慢性硬膜下血肿治疗效果及各组硬膜下血肿吸收时间。结果 C组总有效率显著高于A组和B组(P0.05),C组硬膜下血肿吸收时间为(25.1±0.3)d;B组硬膜下血肿吸收时间为(38.2±1.6)d,A组硬膜下血肿吸收时间为(41.2±1.8)d;C组硬膜下血肿吸收时间优于A组和B组(t=19.814,P=0.0000.05)。结论针对慢性硬膜下血肿使用40 mg/d的阿托伐他汀治疗,能更好地提高患者临床治疗效果,促进神经功能恢复,值得推广。     

匹伐他汀与阿托伐他汀治疗高脂血症的比较

目的比较匹伐他汀（2mg）与阿托伐他汀（10mg）治疗高瞻血症的有效性和安全性。方法采用随机、阳性对照、单盲的研究方法。将经过4周饮食控制及安慰剂洗脱的高脂血症患者68例随机分为阿托伐他汀组（35例）与匹伐他汀组（33例）,治疗8周后,观察其血脂水平变化。结果治疗8周后与治疗前相比,两组总胆固醇、低密度脂蛋白胆固醇、三酰甘油水平均降低,高密度脂蛋白胆固醇均升高,治疗前后血脂变化幅度差异均无统计学意义（P〉0．05）。两组间不良反应发生率比较,差异无统计学意义（P〉0．05）。结论匹伐他汀在疗效和安全性上不劣于阿托伐他汀。