辛伐他汀治疗老年冠心病的疗效及安全性研究

目的 观察老年冠心病（CHD）患者中,辛伐他汀不同剂量调脂的有效性和安全性.方法 选择确诊为CHD的老年患者124例,随机分为观察组63例和对照组61例,观察组患者给予辛伐他汀40mg,对照组给予辛伐他汀20mg,均为每晚服药1次.分别于用药前、用药后第6、12、24周空腹采静脉血清,以酶法测定总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、三酰甘油（TG）、肌酶以及肝、肾功能等.结果 用药第6周两组患者的TC和LDL-C均比用药前明显下降,且一直保持到用药24周末（P＜0.05）.第6、12、24周的TC、LDL-C水平在观察组比对照组明显降低（P＜0.05）.观察组患者24周TC达标率（82.8%比64.9%,P＜0.05）和LDL-C达标率（83.0%比64.9%,P＜0.05）明显高于对照组.两组患者谷丙转氨酶（ALT）升高、肌酶升高等副作用的发生率未见明显差异.结论 40mg辛伐他汀能够安全而且更有效地降低 TC和LDL-C水平,使更多的CHD患者的血清胆固醇达到理想标准水平,老年患者亦可耐受此剂量.     

早期强化辛伐他汀治疗急性冠状动脉综合征的研究

目的 :研究两组不同剂量辛伐他汀治疗急性冠状动脉综合征 (ACS)的近期心血管事件影响及安全性。方法 :15 2例ACS患者随机分成 3组。A组常规治疗 ;B组 :辛伐他汀 2 0mg/d ;C组 :辛伐他汀 4 0mg/d ,随访观察 3组患者首次入院后 1个月和 1年的终点事件发生率 (死亡、再发心绞痛或心肌梗死、再入院率 )以及血脂水平、肝肾功能和不良反应。结果 :B组、C组初始 1个月及 1年内的病死率、再发心绞痛、再发心肌梗死及再住院率均较A组明显降低 (均P <0 .0 5 )。B组 1个月、1年病死率下降分别为 3.92 %、7.84 % ,C组 1个月、1年病死率下降分别为 3.76 %、7.6 0 % ;C组与B组比较 ,初始 1个月内心绞痛、心肌梗死再发生率差异有统计学意义 (P<0 .0 5 )。但对 1年内病死率及心绞痛、心肌梗死的再发生率差异无统计学意义 (均P >0 .0 5 )。 2、6、12个月血脂监测显示B组、C组均能有效降低总胆固醇、低密度脂蛋白胆固醇、三酰甘油水平。B组 2例、C组 3例出现恶心、纳差等消化道症状 ;B组 1例、C组 2例出现转氨酶增高 1～ 3倍。结论 :辛伐他汀 2 0、4 0mg用于ACS早期治疗均安全有效 ,均能有效降低近期冠心病事件发生率和病死率 ,且提示疗效与剂量成正相关     

Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on serum lipid levels in hypercholesterolaemic post-menopausal women.

AIMS: To evaluate the effects of simvastatin only or combined with continuous hormone replacement therapy on the serum lipid profile in hypercholesterolaemic post-menopausal women. METHODS AND RESULTS: One hundred hypercholesterolaemic post-menopausal women were given either simvastatin 10 mg daily together with oestrogen 0.625 mg and medroxyprogesterone 2.5 mg daily (HRT+simvastatin group) (n:50) or simvastatin 10 mg daily (simvastatin only group) (n:50) in a prospective manner. Serum total, low density lipoprotein, and high density lipoprotein cholesterol and triglyceride levels were measured at baseline, at 3 and 6 months. The initial mean (+/-SD) cholesterol values were as follows for the HRT+simvastatin group and the simvastatin only group, respectively: total cholesterol 240. 0+/-28.0 and 248.9+/-28.2 mg x dl(-1); low density lipoprotein cholesterol 174.7+/-25.6 and 175.1+/-25.9 mg x dl(-1); high density lipoprotein cholesterol 37.2+/-5.0 and 39.9+/-7.3 mg x dl(-1). Compared with the baseline, total and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol levels increased significantly at 3 and 6 months in both groups. However, the mean percent reduction in total cholesterol and low density lipoprotein cholesterol was significantly greater in the HRT+ simvastatin group compared with the simvastatin only group both at 3 months (12.3+/-7.0% vs 8.9+/-6.2%;P<0.01; and 19.0+/-10.6% vs 13.2+/-10.4%;P< 0.005, respectively) and at 6 months (14.6+/-7.7% vs 11.3+/-7.4%;P<0.05 and 23.3+/-9.7% vs 15.8+/-12.3%;P<0.005, respectively). The mean percent increase in serum high density lipoprotein cholesterol concentrations was also significantly greater in the HRT+simvastatin group compared with the simvastatin only group at both times (14.6+/-11.8% vs 9.8+/-11.8%;P<0.005, at 3 months, and 21.3+/-15.2% vs 11.1+/-12.5;P<0.005, at 6 months, respectively). Furthermore, significantly more patients in the HRT+simvastatin group than in the simvastatin only group attained their target treatment goals dictated by the National Cholesterol Education Program Adult Treatment Panel II Guidelines. Although the mean percent decrease in triglyceride levels was significantly greater in the HRT+simvastatin group at 3 months, the significance disappeared at 6 months. CONCLUSION: The combination of simvastatin and continuous combined hormone replacement therapy seems to be more effective than simvastatin only in the treatment of hypercholesterolaemia in post-menopausal women.     

辛伐他汀联合普罗布考治疗缺血性脑卒中对患者血清 hs－CRP、FT3、FT4水平的影响

目的：观察辛伐他汀联合普罗布考治疗缺血性脑卒中对患者血清超敏C反应蛋白（ hs－CRP）、游离三碘甲状腺原氨酸（ FT3）、甲状腺素（ FT4）水平的影响。方法将107例缺血性脑卒中患者随机分为试验组54例和对照组53例。试验组给予辛伐他汀联合普罗布考治疗,对照组仅给予普罗布考治疗,连续治疗21d。比较2组患者治疗前后血清hs－CRP、FT3、FT4变化。结果治疗前2组患者血清hs－CRP、FT3、FT4水平差异无统计学意义（ P＞0．05）。治疗后2组患者hs－CRP均有所降低,但试验组患者降低幅度大于对照组,差异均有统计学意义（ P＜0．05）;治疗后2组FT3、FT4水平均增高,但试验组患者增幅大于对照组,差异均有统计学意义（P＜0．05）。结论辛伐他汀联合普罗布考治疗缺血性脑卒中可显著降低患者血清hs－CRP水平,增高FT3、FT4水平,使其趋于正常水平。     

不同剂量辛伐他汀早期干预对急性冠状动脉综合征患者血清C反应蛋白的影响

目的观察不同剂量辛伐他汀早期干预对急性冠状动脉综合征(ACS)患者血清高敏C反应蛋白(hs-CRP)水平的影响及调脂作用与安全性。方法75例ACS患者随机分为三组,A组为优化药物治疗,B组为优化药物治疗加辛伐他汀20mg/d,C组为优化药物治疗加辛伐他汀40mg/d,均治疗4周,健康对照组不予治疗。分别于用药前及疗程结束后查hs-CRP及血脂水平,同时观察用药安全性。结果(1)ACS患者hs-CRP、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)含量显著高于健康对照组(P<0.01)。(2)辛伐他汀20mg与40mg治疗4周后,均能显著降低hs-CRP、TC、LDL-C及TG水平(P均<0.01),其中40mg剂量组的疗效明显优于20mg剂量组。结论ACS患者hs-CRP显著升高,存在明显的炎症反应,早期大剂量辛伐他汀调脂干预,能安全更有效地抑制此类炎症反应及脂质过氧化损伤,且呈剂量依赖性。     

Clinical Observation on the Aggressive Lipid-lowering Treatment with Simvastatin on the Aged Patients with Coronary Artery Disease

Objectives To find out the efficient dose and safety of simvastatin (Zocor) on the aged patients with coronary artery disease (CAD) for aggressive lipid-lowering treatment. Methods Select 95 aged patients with CAD combined with primary hyperlipemia and give them 20mg/day of simvastatin for treatment. According to the therapeutic target of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) regulate the dosage of simvastatin in follow-up. Observe 12-18 months. Results After treatment, the TC, LDL-C and triglycerides(TG) of the patients reduced by 40%，52% and 26% respectively, while there was no significant change in high-density lipoprotein cholesterol (HDL-C). The apolipoprotein A1 arose by 14.4%, while the apolipoprotein B lowered by 25.0%. The ratio of LDL-C to HDL-C was reduced to 1.96. In the 6^th month, the 12^th month and the 18th month, respectively, 86%, 93% and 95% of the patients took 10mg/day of simvastatin and the result was their TC≤140mg/dL(3.7mmol/L) and LDL-C≤70mg/dL(1.8mmol/L).There was no special side-effect. Multi-factor analysis indicated the age of the patients was a significant factor affecting the adjustment of the dosage of simvastatin.Conclusions The therapeutic result of simvastatin on the aged patients with CAD for aggressive lipid-lowring treatment is definite, safe and the dose is lower as well.     

辛伐他汀对兔粥样硬化髂动脉P-选择素、细胞间粘附分子-1表达的影响

目的研究辛伐他汀对兔粥样硬化髂动脉组织P-选择素(P-selectin )、细胞间粘附分子-1(ICAM-1)表达的影响. 方法 30只雄性新西兰大白兔,分别予普通饲料喂养(正常对照组8只)及高脂饲料喂养(基础对照组10只,辛伐他汀组12只).正常对照组喂养6周后处死.高脂饲料喂养2周后行髂动脉内膜球囊损伤术;术后辛伐他汀组每只予辛伐他汀15 mg/d;分组喂养4周后处死所有动物,取一侧病变髂动脉做病理切片;取另一侧抽提总RNA和总蛋白,分别应用免疫组化方法、半定量逆转录多聚酶链式反应和Western蛋白印迹测定P-选择素和ICAM-1 mRNA和蛋白质水平的表达. 结果辛伐他汀可以显著降低兔血浆总胆固醇,正常对照组、基础对照组和辛伐他汀组动脉壁P-选择素 mRNA/β-actin mRNA的相对值分别为0.12±0.04、0.51±0.06、0.27±0.06,相互间差异有显著性(P<0.05);ICAM-1 mRNA/3-磷酸甘油脱氢酶(GAPDH) mRNA比值分别为0.25±0.08、0.91±0.10、0.47±0.09,相互间差异有显著性(P<0.05);P-选择素为6.41±1.64、14.38±2.56、9.47±1.69, 相互间差异有显著性(P<0.05);ICAM-1为4.71±1.64、14.03±2.05、6.78±1.39, 相互间差异有显著性(P<0.05);免疫组化结果与之相一致. 结论辛伐他汀可以显著降低兔粥样硬化髂动脉组织P-选择素和ICAM-1的表达.     

辛伐他汀对小鼠胰腺β细胞功能的影响及机制研究

 目的：观察辛伐他汀对小鼠胰腺β细胞株MIN6胰岛素分泌功能的影响并探讨其可能机制。方法：将MIN6细胞随机分为正常对照组和低、中、高浓度辛伐他汀组,分别用含0、2、5、10 μmol/L辛伐他汀和15%胎牛血清的高糖DMEM培养基培养48 h。采用放射免疫分析法检测辛伐他汀对MIN6细胞胰岛素分泌功能的影响;生物化学发光法测定细胞内ATP含量;用实时荧光定量PCR检测内向整流钾离子通道62（Kir62）、电压依赖性钙离子通道12（CaV12）及葡萄糖转运体2（GLUT2）mRNA表达水平;用Western印迹检测Kir62、CaV12及GLUT2蛋白表达水平。结果：5和10 μmol/L的辛伐他汀能够明显减少MIN6细胞胰岛素的合成及分泌（P<005）;辛伐他汀处理组MIN6细胞内ATP水平较正常对照组明显降低（P<005）;辛伐他汀各处理组MIN6细胞Kir62 mRNA表达水平较正常对照组明显上调（均P<001）,5和10 μmol/L辛伐他汀组CaV12 mRNA水平明显下调（均P<001）,GLUT2 mRNA表达水平明显下调（P<005）;5和10 μmol/L辛伐他汀处理组Kir62蛋白表达较正常对照组明显升高（均P<001）,10 μmol/L辛伐他汀处理组CaV12及GLUT2蛋白表达水平明显下降（均P<001）,5 μmol/L辛伐他汀组CaV12蛋白表达水平较正常对照组亦有明显下降（P<001）。结论：辛伐他汀对小鼠胰腺β细胞株MIN6胰岛素的合成和分泌具有一定的抑制作用。辛伐他汀可能通过抑制MIN6细胞内ATP的生成以及上调MIN6细胞Kir62、下调CaV12和GLUT2的表达从而影响其胰岛素的合成和分泌。     

Development of calcium phosphate/calcium sulfate biphasic biomedical material with hyaluronic acid containing collagenase and simvastatin for vital pulp therapy

ObjectiveIn vital pulp therapy (VPT), a barrier is created with appropriate capping to protect the remaining pulp and thus maintain pulp vitality. Here, we evaluated the feasibility of a biphasic calcium phosphate cement (CPC)–calcium sulfate hemihydrate (CSH) biomaterial containing simvastatin (Sim) and collagenase (Col) for VPT.MethodsCombinations of varying CPC and CSH concentrations were analyzed for their handling properties and setting times, with their structures observed through scanning electron microscopy–energy dispersive X-ray spectrometry (SEM-EDS). Drug release patterns of simvastatin and collagenase combined with CPC–CSH (CPC–CSH–Sim–Col) were also analyzed, followed by biocompatibility and bioactivity tests on human dental pulp stem cells (hDPSCs) and in vivo animal study in canine models; the in vivo results were obtained through microcomputed tomography and histological analysis.ResultsThe results revealed that 70 wt% CPC (CPC7) with 30 wt% CSH (CSH3) exhibited optimal setting time and porous structure for clinical use. The cell viability and cytotoxicity analysis demonstrated that CPC7–CSH3 with or without simvastatin or collagenase did not injure hDPSCs. In vivo, the CPC7–CSH3–Sim–Col induced dentin bridge formation.SignificanceCPC7–CSH3–Sim–Col in this study has great potential as a VPT biomaterial to enhance the dentin bridge formation.