Objective To study the effect and mechanism of atorvastatin on improving airway function of mice with chronic obstructive pulmonary disease (COPD) by inhibiting the expression of inducible nitric oxide synthase (iNOS). Methods Wild type (WT) mice were randomly divided into WT control group, WT+COPD group, WT+COPD+atorvastatin group, NC lentivirus group, NC lentivirus+COPD group, NC lentivirus+COPD+atorvastatin group, and iNOS lentivirus+COPD+atorvastatin group. Lung specific iNOS knockout (KO) mice were randomly divided into KO control group and KO+COPD group. The COPD model was established by passive inhalation of cigarette smoke. Atorvastatin (10 mg·kg–1·d–1) was given by gavage, and the negative control (NC) lentivirus or iNOS lentivirus was given by tail vein injection. The lung function indexes including peak inspiratory flow (PIF) and peak expiratory flow (PEF), the number of neutrophils (N), eosinophils (E), lymphocytes (L) and Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), the expression levels of iNOS, endothelium nitric oxide synthase (eNOS) and neural nitric oxide synthase (nNOS) in lung tissue were measured. Results Compared with WT control group, the levels of PIF and PEF decreased, typical pathological changes of COPD appeared in lung tissue, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS, eNOS and nNOS in lung tissue increased in WT+COPD group (all P<0.05). After atorvastatin intervention, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS in lung tissue decreased in WT+COPD+atorvastatin group (all P<0.05). After specific knockout of iNOS in lung tissue, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF decreased in KO+COPD group (all P<0.05). After overexpression of iNOS by tail vein injection of lentiviral, the levels of PIF and PEF decreased, the pathological changes of COPD in lung tissue aggravated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF increased in iNOS lentiviral+COPD+atorvastatin group (all P<0.05). Conclusion The effect of atorvastatin on improving airway function and inflammatory response of COPD mice is related to the inhibition of iNOS expression.
Objective To observe the effects of different doses of atorvastatin on bleomycin-induced pulmonary fibrosis in rats. Methods Seventy-five healthy female SD rats were randomly divided into five groups ( 15 rats in each group) , ie. a normal group , a model group, a 10 mg/ kg atorvastatin-treated group, a 20 mg/ kg atorvastatin-treated group, and a 40 mg/ kg atorvastatin-treated group. The rats in the model group and treatment groups were instilled with bleomycin in trachea( 5 mg/kg) , and the normal group were instilled with equal volume of normal saline. The treatment groups were gastric gavaged with different doses of atorvastatin each day from2 nd day on after instillation, and the normal group and model group were gavaged with normal saline. Blood samples were obtained from abdominal aorta in five rats in each group and blood gas analysis was performed on1st week, 2nd week and 4th week respectively after BLM instillation. Then the animals were killed and lung tissue samples were harvested for histopathology study. HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.Histoimmunochemical stain were used to determine the protein levels of transforming growth factor-β1 ( TGF-β1 ) and connective tissue growth factor( CTGF) in pulmonary tissues. Results The arterial partial pressure of oxygenate ( PaO2 ) in the treatment groups were increased gradually with the increasing of therapeutic dose at each time point and decreased with prolongation of time in the same group. The protein levels of TGF-β1 and CTGF in pulmonary tissues were decreased gradually with prolongation of time. TGF-β1 and CTGF expressed obviously less in the treatment groups than those in the model group at each time point .The higher therapeutic doses were, the less the expressions of TGF-β1 and CTGF were. Conclusion Atorvastatin has remarkable inhibitory effects on BLM-induced pulmonary fibrosis of rats in a dose- and timedependentmanner.
ObjectTo observe the clinical efficacy and safety of the combination therapy of atorvastatin and JiangZhi Decoction (ZJD) for primary hyperlipidemia (Tan Zhuo Zu E Zheng) and to analyze the interactions of drugs in hypolipidemic effect.
MethodsA 2*2 factorial design, single-blind, stratified randomized controlled trial according to the level of lipid was conducted. Primary hyperlipidemia (Tan Zhuo Zu E Zheng) patients met the inclusion criteria were divided into 5 groups:ATV 10 mg group (group A), ATV 20 mg group (group B), ATV 10 mg+JZD group (group C), ATV 20 mg+JZD group (group D), JZD group (group E). After two weeks treatment, the efficacy and safety among the 5 groups were compared.
ResultsA total of 92 patients were included, of which, 20 were in group A, 25 in group B, 21 in group C, 17 in group D, and 9 in group E. The results showed that:(1) There was no significant difference between group C and group B in the reduction of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (PTC=0.226, PLDL-C=0.818). (2) The results of 2*2 factorial analysis showed that, there was no significant interaction between TCM factor and western medicine factor (PTC=0.605, PLDL-C=0.843). (3) There were no significant differences in safety outcomes among 5 groups (all P values >0.05).
ConclusionATV 10 mg+JZD and ATV 20 mg have a similar efficacy in reducing TC and LDL-C. There is no obvious interaction between JZD and ATV in hypolipidemic effect, and the combination therapy of ATV and JZD is safe.
Objective To systematically assess the effectiveness and safety of atorvastatin in patients with dilated cardiomyopathy (DCM) complicating chronic heart failure (CHF). Methods Databases including PubMed, The Cochrane Library, EMbase, CNKI, CBM, and VIP were searched from inception to November 2011 to collect randomized controlled trials (RCTs) on atorvastatin for DCM accompanied with CHF. According to the inclusion criterion, relevant articles were screened. Then we extracted data, assessed quality, and performed meta-analysis using RevMan 5.0. Results A total of 11 RCTs involving 648 patients were included. The result of meta-analyses showed that compared with the control group at the sixth month after treatment, in the atorvastatin group, left ventricular ejection fraction (LVEF) obviously (MD=3.92, 95%CI 1.93 to 5.92, P=0.000 1) and 6-minute walk distance (MD=13.15, 95%CI 5.47 to 20.83, P=0.000 8) increased. Besides, serum level of CRP obviously decreased in the atorvastatin group (MD=1.91, 95%CI 3.03 to 0.79, P=0.000 9). Conclusion Current evidence indicates that atorvastatin, based on routine treatment, can improve cardiac function to some extent, increase LVEF, and reduce serum levels of inflammatory markers for patients with DCM complicating CHF. Therefore, atorvastatin is likely to be a safe and effective drug for non-ischemic cardiomyopathy due to DCM, which still has to be proved by more large-scale and high-quality clinical trials.
ObjectivesTo systematically review the influence of nifedipine combined with atorvastatin on hypertension in patients with hypertension.MethodPubMed, EMbase, The Cochrane Library, CBM, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of nifedipine combined with atorvastatin on hypertension in patients with hypertension from inception to November 20th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 17 RCTs involving 1 838 patients were included. The results of meta-analysis indicated that nifedipine combined with atorvastatin was superior to nifedipine alone on SBP (MD=?8.937, 95%CI?11.913 to ?5.962, P<0.001), DBP (MD=?3.702, 95%CI?6.626 to ?0.778, P=0.013) and total effective rate (RR=1.24, 95%CI 1.07 to 1.44, P=0.003). There was no significant difference between two groups in the incidence of adverse reactions (P>0.05).ConclusionsCurrent evidence shows that nifedipine combined with atorvastatin can significantly improve total effective rate, decrease the level of SBP and DBP, and increasing of dose not increase the incidence of adverse reactions. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
ObjectiveTo investigate the effects of migration and expression from chemokine receptor 4 (chemokine receptor-4, CXCR4) of rat bone marrow mesenchymal stem cells (BMSCs) which were pretreated by atorvastatin (ATV) in vitro.MethodsIsolated, cultivated, identified the BMSCs, pretreated P4-P6 of BMSCs with different concentrations of ATV for 12 hours. The experimental group was divided into control group, 0.1 nM/L (group 0.1 nM), 1 nM/L (1 nM group), 10 nM/L (10 nM group), 100 nM/L (100 nM group), 1 000 nM/L (1 000 nM group). The mRNA and protein of CXCR4 were determined by real time-polymerase chain reaction and Western blot. Immunofluoreseence assay were used to detect the expression levels of CXCR4. The migration ability of BMSCs were measured by transwell chamber.ResultsImmunofluoreseence assay showed the protein level of CXCR4 of group 1 nM and 10 nM were significantly higher than the other group. RT-PCR and Western blot showed the protein and mRNA level of CXCR4 in 10 nM was higher than that in group 1 nM. The migration ability of group 10 nM was higher than 1 nM and control group.ConclusionsATV can be dose-dependent promote expression levels of CXCR4 of BMSCs cultivated in vitro.
ObjectiveTo observe and analyze the short-term efficacy of different statins on acute myocardial infarction in patients with premature coronary heart disease.
MethodWe selected 70 patients with acute myocardial infarction admitted into our hospital for treatment of premature coronary artery disease between January 2012 and June 2013. The patients were randomly divided into experimental group (n=35) and control group (n=35). The experimental group were treated with rosuvastatin, and the control group of patients were given atorvastatin. We observed the rate of overall efficiency within 6 months after treatment, and total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), hepersensitive C-reactive protein (hs-CRP), left ventricular ejction fraction (LVEF), and flow-mediated dilation (FMD) were also observed before and after treatment.
ResultsThe overall efficacy rate in the experimental group at 6 months was 94.3% and in the control group was 88.6% with no significant difference between each other (P>0.05). TG and FMD of patients in the experimental group at 6 months did not significantly change (P>0.05), while LVEF of the experimental group was significantly higher (P<0.05), and hs-CRP, TC, LDL-C, and HDL-C of the experimental group were significantly lower than the control group (P<0.05).
ConclusionsShort-term comprehensive efficacy of rosuvastatin for treatment of premature coronary artery disease in patients with acute myocardial infarction is superior to atorvastatin.
Objective To explore the effects of aggressive lipid lowering therapy and its influence on cardiovascular events using lipitor (20 mg daily) for Chinese people after percutaneous coronary intervention (PCI). Methods We did a double-blind and randomized controlled trial. From July 2005 to June 2006, 120 patients with PCI procedure who were discharged from the Shanghai Chest Hospital were randomly divided into aggressive lipid lowering group (atorvastatin 20 mg daily, n=60) and an ordinary lipid lowering group (atorvastatin 10 mg daily, n=60). The trial treatment was administered from the day of PCI to the third month after PCI. Atorvastatin at 10 mg daily was then used until one year after PCI. Blood biochemistry, cardiovascular events and drug adverse reactions were compared between the two groups. Results Among the 120 patients, 5 discontinued treatment and 4 more withdrew from the study. Therefore 115 and 111 were included in our main analyses [Comment from Mike: it is not ITT if the 5 who discontinued treatment are excluded] and a per-protocol (PP) analysis, respectively. Baseline clinical characteristics were comparable between the two groups. The reduction in TG and the increase in HDL-C were similar between the two groups (Pgt;0.05), but the reductions in LDL-C and TC were significantly different between the two groups (Plt;0.05). This was observed from the beginning of follow-up to the third month after PCI. In the PP analysis, the percentage of patients whose LDL-C met the predefined requirement at the third month in the 20 mg group was significantly higher than in the group receiving the lower dose (87.03% vs. 70.17%, P=0.031). A similar result was also obtained if the patients who withdrew were retained in the analysis (P=0.044). The change in C reaction protein (CRP) from baseline at the first and the third month was significantly different between the two groups (Plt;0.05), but become relatively stable at the sixth month (Pgt;0.05). The mean follow-up duration was 6.5±3.0 months in the higher dose group, with 1 case of recurring angina pectoris and 1 case of revascularization were identified. It was 7.2±3.6 months in the 10 mg daily group, with 3 cases of recurring angina pectoris, 1 case of nonfatal myocardial infarction, 2 cases of revascularization and 1 case of sudden cardiogenic death. The difference in the Kaplan-Meier event curves was of borderline statistical significance from the fourth month (P=0.048). Drug adverse reactions were mild and myopathy was not identified in any patients. Conclusions After PCI procedure, the use of atorvastatin 20 mg daily for aggressive lipid lowering was safe and effective.
【摘要】 目的 探討阿托伐他汀強化降脂治療和左旋氨氯地平聯用對高血壓患者血壓的影響。 方法 選擇2009年1月-2010年11月住院及門診原發性高血壓合并高脂血癥患者196例，均給予左旋氨氯地平和阿托伐他汀治療8周后，復查血脂，從其中選擇血脂正常者120例，隨機分為對照組（單用左旋氨氯地平組）和治療組（繼續左旋氨氯地平聯用阿托伐他汀），繼續治療20周后的血壓情況。 結果 兩組治療20周后，治療組收縮壓和舒張壓均較對照組下降明顯，組間差異有統計學意義（Plt;0.01），治療組優于對照組。 結論 高血壓合并高脂血癥患者，使用左旋氨氯地平降壓和阿托伐他汀降脂治療時，在血脂降至正常后，繼續同時左旋氨氯地平降壓和阿托伐他汀強化降脂治療，降壓效果優于單用左旋氨氯地平。【Abstract】 Objective To investigate the effects of levamlodipine combined with atorvastatin on blood pressure in patients with primary hypertension. Methods Between January 2009 and November 2010, 196 patients with hypertension and hyperlipidemia in the outpatient and inpatient departments of our hospital were given levamlodipine and atorvastatin for 8 weeks, after which 120 patients with normal blood lipid were chosen and randomly divided into the control group (treated only by levamlodipine) and the treatment group (treated by levamlodipine combined with atorvastatin). After 20 weeks of the treatment, we observed their blood pressure. Results After twenty weeks of treatment, the diastolic and systolic pressure was significantly lower in the treatment group than that in the control group (Plt;0.01). Conclusion For patients with hypertension and hyperlipidemia who have undergone the treatment by levamlodipine and atorvastatin, after their blood lipid level decreases to normal, the continuous enhanced treatment by the two drugs has a better efficacy compared with the therapy of single levamlodipine in decreasing the blood lipid.
