瑞舒伐他汀和阿托伐他汀的降脂疗效与ABCB1基因多态性的相关性

目的 研究瑞舒伐他汀和阿托伐他汀降脂疗效与ABCB1 G2677T基因多态性的相关性.方法 采用实用性随机对照试验,将收集符合标准的483例ABCB1 G2677T基因检测患者分为瑞舒伐他汀组和阿托伐他汀组,分析瑞舒伐他汀和阿托伐他汀降脂疗效与ABCB1基因多态性之间的相关性.结果 483例患者的ABCB1 G2677...     

小剂量阿托伐他汀和瑞舒伐他汀对高脂血症患者的影响

目的探讨小剂量阿托伐他汀和瑞舒伐他汀对高脂血症患者的影响。方法2011年6月至2012年9月在佛山市南海区第五人民医院内科门诊就诊的LDL-C〉200mg／dL的原发性高胆固醇血症患者106例,随机分为两组,A组52例（瑞舒伐他汀,10mg／天）,B组54例（阿托伐他汀,20mg／天）,间隔3,6,9和12个月定期对患者进行检查。每次随访时都采集血液样本,并对患者的不良反应进行仔细评估。总共随访48周。在开始药物研究前,采集了每个患者的禁食（12小时）血液样本来确定血浆中胆固醇、甘油三脂、LDL-C、HDL-C、non-HDL-C、谷丙转氨酶、谷草转氨酶等基础值。这些测量值将在瑞舒伐他汀和阿托伐他汀治疗48周后再进行一次。最终比较两组间总治疗时间为48周后的血脂谱的变化。结果在经过48周的治疗后,血浆中TC、LDL-C、non-HDL-C和TG水平与基线值相比下降了（A％：-35．77,-44．32,-43．12,-36．41,P〈0．001）;HDL-C比基线值下降,但区别不明显（A％：-2．04,P〉0．05）。48周后,A组患者比B组患者在血浆中LDL-C水平上有显著下降（-44．32％VS-30％,P〈0．005）。与阿托伐他汀相比,瑞舒伐他汀对总胆固醇、甘油三酯和非高密度脂蛋白胆固醇水平上也产生了更大的降低俨〈0．005）。而血浆中HDL-C水平并未受到显著影响。结论对原发性高胆固醇血症的高危患者而言,瑞舒伐他汀（10mg／天）比阿托伐他汀（20mg／天）在降低血浆中LDL-C水平方面要更有效,能够达到更理想的LDL-C水平,并改善其他血脂指标,而且,两种治疗方法在48周中耐受性良好。     

瑞舒伐他汀与阿托伐他汀治疗冠心病的临床效果比较

目的 比较瑞舒伐他汀与阿托伐他汀治疗冠心病的临床效果.方法 选取2018年5月—2020年4月云南省富宁县人民医院收治的冠心病患者74例,根据随机分组对照原则分为观察组和对照组,各37例.在综合治疗基础上,对照组予阿托伐他汀钙片治疗,观察组则予瑞舒伐他汀钙片治疗,1个月为1个疗程,2组均持续治疗3个月.比较2组治疗效果...     

冠心病采用瑞舒伐他汀和阿托伐他汀治疗的临床效果探析

目的探讨冠心病采用瑞舒伐他汀和阿托伐他汀治疗的临床效果。方法选取我院接收的84例冠心病患者作为本次的研究对象,以治疗方式的不同将其分为观察组和对照组,每组42例,观察组患者采用瑞舒伐他汀治疗,观察组患者采用阿托伐他汀治疗,比较两组患者的临床疗效。结果两组患者治疗前TC、TG、LDC-C及HDC-C比较均无较大差异(P<0.05),治疗后两组患者TC、TG、LDC-C均有所下降,HDC-C均有所上升,但观察组的改善程度明显优于对照组(P<0.05);观察组患者的不良反应发生率明显低于对照组(P<0.05)。结论给予冠心病患者瑞舒伐他汀治疗可有效的改善患者血脂情况,且不良反应较少,有较高的应用价值,可推广应用。     

阿托伐他汀的基因多态性研究进展

阿托伐他汀是临床上广泛使用的调血脂药物,长期使用能够预防并减少动脉粥样硬化性心血管疾病（ASCVD）的发生,但阿托伐他汀的疗效具有显著的个体间差异,有些个体不能达到预期调脂目标值或出现严重的不良反应。这与个体间的遗传多样性有关,遗传变异可导致药物体内处置不同,从而导致临床疗效和不良反应有差异。对影响阿托伐他汀药物反应的药物代谢酶、药物转运体、药物作用靶点及与脂质代谢相关基因多态性加以综述,并从基因水平上探讨不同个体使用阿托伐他汀的药动学、药效学及不良反应易感性差别的原因。     

瑞舒伐他汀与阿托伐他汀治疗冠心病的疗效比较

目的比较瑞舒伐他汀与阿托伐他汀治疗冠心病的疗效。方法选取我院在2015年9月至2016年7月收治的134例冠心病患者作为观察对象,按照计算机数字法分为常规组和试验组,每组之中67例患者,分别采用阿托伐他汀和瑞舒伐他汀进行治疗,观察并比较两组治疗后血脂改善情况和总体治疗效果。结果经过3周治疗后,试验组HDL-C与常规组比较明显升高,其LDL-C、TG、TC与常规组比较则明显降低,两组血脂改善情况比较结果显示,试验组优于常规组(P<0.05);两组总体治疗效果比较,常规组治疗总有效率低于试验组(P<0.05)。结论与阿托伐他汀比较,瑞舒伐他汀改善冠心病患者血脂水平和总体治疗效果优势明显,值得临床优先选择和全面普及。     

阿托伐他汀与瑞舒伐他汀对冠心病患者的疗效与安全性对比观察

目的:对比分析阿托伐他汀与瑞舒伐他汀在冠心病患者中应用的疗效与安全性。方法:回顾性分析127例冠心病患者的临床资料,根据调脂药物的种类分为2组:阿托伐他汀组44例,基本用量20 mg·d^-1,用药(7.6±1.9)个月;瑞舒伐他汀组83例,基本用量10 mg·d^-1,用药(7.9±2.1)个月。分别统计治疗前、治疗后1,2,4,8,12周及末次复查时血脂水平,并记录药物不良反应。结果:患者接受药物治疗1周时各指标较治疗前均无明显变化(P>0.05);治疗2周时,两组TG、TC及LDL-C水平均较治疗前降低(P<0.05),但组间差异无统计学意义(P>0.05);药物治疗4,8,12周时,两组TG、TC及LDL-C较治疗前降低(P<0.05),瑞舒伐他汀组LDL-C水平低于阿托伐他汀组,而LDL-C的降幅和血脂达标率均高于阿托伐他汀组,差异均有统计学意义(P<0.05)。至末次复查,两组TG、TC及LDL-C均较基线水平显著降低(P<0.05),阿托伐他汀组LDL-C的降幅低于瑞舒伐他汀组(P<0.05)。两组共发生药物相关性不良反应9例,其中阿托伐他汀组4例(9.1%),瑞舒伐他汀组5例(6.0%),两组差异无统计学意义(P>0.05)。结论:瑞舒伐他汀和阿托伐他汀均于用药2周时表现出较好的调脂疗效,10 mg·d^-1瑞舒伐他汀的调脂疗效优于20 mg·d^-1阿托伐他汀,两药不良反应发生率均较低,安全性无明显差异。     

阿托伐他汀对oxLDL诱导泡沫细胞Lkn-1表达的影响

目的观察阿托伐他汀对OX-LDL诱导U937细胞形成泡沫细胞过程中Lkn-1表达的影响,探讨阿托伐他汀抗AS的作用机制。方法在由O．1μmol／L佛波脂（PMA）诱导分化人U937巨噬细胞中加入100mg／Lox—LDL及不同浓度（0．1、1、10μmol／L）的阿托伐他汀共同孵育24h,分别用酶联免疫吸附试验（ELISA）和RT-PCR方法检测培养细胞上清中Lkn-1的表达变化。结果OX-LDL组较正常对照组Lkn-1的表达明显增加（P〈0．05）。给药各组较OX-LDL组Lkn-1明显减少（P〈0．05）。且随阿托伐他汀浓度的增加Lkn-1表达呈逐渐减少的趋势（P〈0．05）。结论阿托伐他汀能抑制ox—LDL诱导U937细胞系形成泡沫细胞过程炎症因子Lkn-1的表达和分泌,可能为其抗动脉粥样硬化的重要机制之一。     

Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA in vivo remain unclear. We generated a mouse model lacking the initiating enzymes, CYP7A1 and CYP27A1, in the two main pathways of BA synthesis. Because females are more susceptible to BA related diseases, such as intrahepatic cholestasis of pregnancy, we expanded this model into female mice. The null mice of Cyp7a1 and Cyp27a1 were crossbred to create double knockout (DKO) mice. BA concentrations in female DKO mice had reductions in serum (63%), liver (83%), gallbladder (94%), and small intestine (85%), as compared to WT mice. Despite low BA levels, DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation, synthesis, conjugation, and transport. Additionally, through treatment with a synthetic FXR agonist, GW4064, female DKO mice responded to FXR activation similarly to WT mice.     

Intestinal flora induces the expression of Cyp3a in the mouse liver

1. In order to determine the effects of intestinal flora on the expression of cytochrome P450 (CYP), the mRNA expression of CYP was compared between specific pathogen-free (SPF) and germ-free (GF) mice.

2. Most of the major CYP isozymes showed higher expression in the livers of SPF mice compared with GF mice.

3. Nuclear factors such as pregnane ? receptor (PXR) and constitutive androstane receptor (CAR), as well as transporters and conjugation enzymes involved in the detoxification of lithocholic acid (LCA), also showed higher expression in SPF mice.

4. The findings suggest that in the livers of SPF mice, LCA produced by intestinal flora increases the expression of CYPs via activation of PXR and CAR.

5. Drugs such as antibiotics, some diseases and ageing, etc. are known to alter intestinal flora. The present findings suggest that such changes also affect CYP and are one of the factors responsible for individual differences in pharmacokinetics.

     

Effects of lipopolysaccharide-stimulated inflammation and pyrazole-mediated hepatocellular injury on mouse hepatic Cyp2a5 expression

Murine hepatic cytochrome P450 2a5 (Cyp2a5) is induced during hepatotoxicity and hepatitis, however, the specific regulatory mechanisms have not been determined. We compared the influence of acute inflammation elicited in vivo by bacterial endotoxin lipopolysaccharide (LPS) and liver injury caused by the hepatotoxin pyrazole on hepatic Cyp2a5 expression in mice. Pyrazole treatment resulted in statistically significant increases in levels of Cyp2a5 mRNA, protein and catalytic activity by 540, 273 and 711%, respectively (P<0.05). In LPS-treated livers Cyp2a5 expression was significantly reduced compared to controls at the mRNA (46%) protein (35%), and activity (23%) levels (P<0.05). Treatment of mice with recombinant murine interleukin-1 beta and interleukin-6 had no significant effect on Cyp2a5 mRNA and protein levels. Liver injury, as assessed by serum alanine aminotransferase, was greater with pyrazole than with LPS treatment (609 vs 354% of control levels respectively). ER stress, determined by hepatic glucose regulated protein 78 (grp78) levels, was greater with pyrazole (185% of controls) than with LPS (128% of controls). In pyrazole-treated liver, overexpression of immunoreactive grp78 protein revealed that ER stress was localized to pericentral hepatocytes in which Cyp2a5 was induced. Evidence of glycogen loss and membrane damage in these cells was suggestive of oxidative damage. Moreover, vitamin E attenuated Cyp2a5 induction by pyrazole in vivo. These results suggest that induction of Cyp2a5 that has been observed in mouse models of hepatitis and hepatoxicity may be related to oxidative injury to the endoplasmic reticulum of pericentral hepatocytes rather than exposure to pro-inflammatory cytokines.