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。     

阿托伐他汀致肝损伤的机制

阿托伐他汀为3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶选择性抑制剂,是一种具有良好降血脂效果的降脂药。阿托伐他汀可引起剂量依赖性血清氨基转移酶升高,常伴有肝脏肿大、黄疸、直接胆红素升高、凝血酶原时间延长等。阿托伐他汀致肝损伤的类型有:细胞毒型、胆汁淤积型和混合型。阿托伐他汀致细胞毒型肝损伤的机制可能是通过竞争性抑制HMG-CoA还原酶,引起肝细胞染色体DNA断裂和细胞形态学变化,导致肝细胞凋亡所致。阿托伐他汀致胆汁淤积型肝损伤的机制可能是使肝细胞窦状隙膜或胆管侧膜上转运体表达减少或功能障碍,或通过抑制胆盐和胆汁酸排泄相关转运蛋白的活性所致。防治阿托伐他汀致肝损伤措施包括:应用阿托伐他汀前,应检测患者肝脏功能,了解病史、其他用药及饮酒习惯等;建议从小剂量开始应用。因服用阿托伐他汀致轻中度转氨酶升高者可减少用药剂量,服用保肝利胆等药物;严重肝损伤者应立即停药并对症治疗。     

阿托伐他汀对老年高血压病患者降压作用的影响

目的探讨阿托伐他汀长期使用对已接受降压治疗的高血压病患者血压的影响。方法选取2007年8月至2008年4月在我院干部病房住院且出院后门诊随访、规律服用降压药物治疗的患者62例,按10年心血管危险分层及低密度脂蛋白胆固醇（LDL-C）水平分为治疗组（34例）和对照组（28例）,治疗组除常规降压治疗外,每日加服阿托伐他汀从10 mg开始,根据血脂水平调整剂量,平均为（13.9±6.1）mg.d-1,对照组给予常规降压治疗。比较两组在治疗前及治疗6个月时的动态血压变化。结果对照组治疗前后血压无明显变化（均P〉0.05）;治疗组24 h平均收缩压（24 h平均SBP）、24 h平均脉压（24 h平均PP）在治疗6个月时较治疗前均下降,差异均具有统计学意义（均P〈0.05）,24 h平均舒张压（24h平均DBP）治疗前后无显著变化（P〉0.05）。结论阿托伐他汀对高血压病患者具有降低24 h平均SBP、缩小24 h平均PP的作用。     

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。     

阿托伐他汀对兔动脉粥样硬化血管内皮细胞膜超微结构影响的研究

目的探讨纳米水平上阿托伐他汀对兔动脉粥样硬化(atherosclerosis,AS)血管内皮细胞(vascular endothelial cell,VEC)超微结构的影响。方法44只♂新西兰大白兔,随机分为3组,对照组12只,高脂组16只,阿托伐他汀组16只,分别于2、6wk末随机抽取6~8只处死,采血检测血脂,取胸主动脉制作标本,应用原子力显微镜(atomic force micro-scope,AFM)观察。结果AFM50μm大范围扫描可见对照组VEC呈梭形,大小约11.96μm×3.72μm。排列规则,其长轴与血流方向一致;高脂组2、6wk末兔VEC较正常对照组明显变大肿胀,变形,排列紊乱。500nm超微结构扫描正常组细胞膜蛋白由圆形、椭圆形的隆起构成,大小基本一致,隆起光滑饱满,隆起间界线分明;2、6wk高脂组内皮细胞膜蛋白由许多大小不一的隆起构成,形态各异,隆起表面凹凸不平,隆起间有许多孔洞,隆起间界限模糊;阿托伐他汀组2、6wk末VEC超微结构明显改善,更接近正常对照组。同时比较了3组500nm水平下膜蛋白的平均粗糙度(mean roughness,Ra),发现在2、6wk高脂组明显高于正常对照组和药物组,差异具有统计学意义(P<0.01),阿托伐他汀组细胞膜粗糙度高于正常对照组(P<0.01)。结论AFM可直观的观察到AS受损的VEC及细胞膜的超微结构改变,以及阿托伐他汀明显改善AS引起的VEC损伤,从而发挥其降脂外的抗AS作用。     

瑞舒伐他汀与阿托伐他汀治疗冠心病临床对照研究

目的:对比瑞舒伐他汀与阿托伐他汀治疗冠心病的临床疗效。方法:选取某院在2010年11月~2013年11月收治的86例冠心病患者,随机均分成观察组和对照组,每组43例。观察组采用瑞舒伐他汀治疗,对照组采用阿托伐他汀治疗,连续治疗一个疗程(8周)之后,观察两组患者的临床疗效。结果:经治疗后,观察组患者的TG、LDL-C、TC、HDL-C等血指标改善程度均优于对照组,且观察组的治疗总有效率(93.02%)明显高于对照组(86.05%),两组数据差异显著具有统计学意义(P0.05)。结论:在治疗冠心病时,瑞舒伐他汀的效果要优于阿托伐他汀,值得临床推广。     

阿托伐他汀对血管新生的促进作用

目的探讨阿托伐他汀对血管新生的促进作用及其作用机制。方法建立野生型C3H／He小鼠下肢缺血模型,观察用药后肢体血流、毛细血管数、血管内皮生长因子（VEGF）蛋白表达。并行离体实验（血管新生共同培养）,计数血管样结构物管腔形成数。结果阿托伐他汀使实验小鼠术后缺血肢血流明显改善,缺血肢与非缺血肢血流面积比明显增加;缺血肢毛细血管密度明显增加,VEGF蛋白表达增强。血管新生共同培养,血管样结构物管腔数明显高于对照组和加入血管新生抑制剂组,但与阳性对照组比较无明显差异。结论阿托伐他汀有促进血管新生的作用。     

瑞舒伐他汀与阿托伐他汀治疗冠心病的疗效对比研究

目的:比较运用瑞舒伐他汀和阿托伐他汀针对冠心病患者展开治疗的临床效果差异。方法:244例冠心病患者随机分为研究组和参照组,每组各122例,参照组患者实施阿托伐他汀药物治疗,研究组患者实施瑞舒伐他汀药物治疗,观察比较两组患者的临床治疗效果。结果:研究组患者的临床治疗有效率明显高于参照组患者,差异有统计学意义(P0.05);研究组患者的血清高密度蛋白胆固醇含量指标和内皮舒张生理功能指标均明显高于参照组患者,其他生理指标均低于参照组,差异有统计学意义(P0.05)。结论:针对临床中收治的经确诊冠心病患者实施瑞舒伐他汀药物治疗,能够获取到较好临床效果,值得在临床医学实践过程中加以推广普及运用。     

阿托伐他汀对血管保护作用的研究进展

动脉粥样硬化(Atheroselerosis,AS)是大多数心脑血管疾病的重要病理基础.阿托伐他汀(atorvastatin)作为一种新型的人工合成降脂药,可降低血浆总胆固醇和低密度脂蛋白胆固醇(LDL-C),并影响机体炎症反应、血管内皮功能、血栓形成等病理生理过程,在延缓动脉粥样硬化进展、减少急性心脑血管事件的发生方面发挥着重要作用.现将阿托伐他汀对血管保护作用的研究进展综述如下.     

阿托伐他汀对高脂饮食大鼠非酒精性脂肪性肝炎的影响

目的观察阿托伐他汀对高脂饮食大鼠非酒精性脂肪性肝炎(NASH)的影响。方法将23只SD大鼠随机分为三组:正常对照组(NC组,8只)、高脂饲养模型组(HF组,7只)和高脂饲养+阿托伐他汀组(HF+AT组,8只)。观察大鼠血清及肝脏各指标的变化,RT-PCR分别检测肝组织核转录因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)及过氧化物酶体增生物激活受体γ(PPARγ)mRNA表达。结果与HF组相比,HF+AT组大鼠血清相关指标明显改善,肝组织脂肪变性及炎症活动得以减轻,肝脏NF-κB及TNF-αmRNA表达降低,PPARγmRNA表达增加(P<0.05或P<0.01)。结论阿托伐他汀能减轻高脂诱导的模型大鼠NASH。     

Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff

The role of beta-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, beta-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension. Although these agents lower blood pressure measured conventionally over the brachial artery with a blood pressure cuff, they do not exert a commensurate effect on blood pressure in the central aorta. Central aortic blood pressure and aortic augmentation index are strong predictors of left ventricular hypertrophy, an independent risk factor for cardiovascular events. Emerging data are illuminating the antihypertensive paradox whereby antihypertensive agents may elicit discordant effects on central and peripheral blood pressure and hemodynamics. Vasodilatory antihypertensives, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, elicit reductions in central aortic blood pressure equal to or greater than that in the brachial artery. Conversely, beta-blockers lower central aortic blood pressure to a lesser degree even when blood pressure measured by sphygmomanometry is reduced substantially. Given the strong relationship between central aortic blood pressure and target organ damage, the effectiveness of beta-blockers may be overestimated in practice on the basis of conventional blood pressure measurements alone. Differences in central and peripheral blood pressure may account for the lack of cardiovascular protection afforded by beta-blockers in clinical trials and could account for a portion of the apparent "benefit beyond blood pressure" reduction with other classes of antihypertensive agents. Future studies should aim to better clarify the role of central aortic blood pressure in the treatment of hypertension. In the meantime, the effects of antihypertensive drugs on blood pressure "beyond the brachial blood pressure cuff" should be considered when prescribing antihypertensive agents for a patient.     

褪黑素对肾血管型高血压大鼠的血压及主动脉舒缩功能的影响

目的　观察褪黑激素 (melatonin ,MT)对两肾一夹(2K1C)高血压大鼠的降压作用 ,并探讨降压作用的血管机制。方法　左肾动脉狭窄法建立两肾一夹高血压大鼠模型 ;无创尾套法测量尾动脉收缩压 ;离体血管功能实验方法记录MT血管作用活性。结果　MT 10mg·kg-1ip可降低 2K1C大鼠血压〔由 (2 3 45± 2 40 )kPa降为 (19 81± 2 78)kPa ,P<0 0 5〕 ;MT(10 -4 mol·L-1)可部分恢复 2K1C大鼠离体主动脉血管环对乙酰胆碱 (Ach)的舒张反应 (P <0 0 1) ,减弱血管对去甲肾上腺素 (NE)的收缩反应 (P <0 0 5 ) ;MT(10 -5～ 10 -3 mol·L-1)明显抑制血管对氯化钾 (KCl)的收缩反应 ,该抑制活性在 2K1C与假手术组中没有差异。结论　MT的血管活性作用是其 2K1C大鼠降压效应的因素之一 ,MT通过其清除自由基与抗氧化功能部分恢复高血压所致血管内皮功能受损与血管平滑肌细胞内氧化状态失调 ,使血管部分恢复正常活性。     

Effect of ascorbic acid supplementation on nitric oxide metabolites and systolic blood pressure in rats exposed to lead

Background:

Extended exposure to low levels of lead causes high blood pressure in human and laboratory animals. The mechanism is not completely recognized, but it is relatively implicated with generation of free radicals, oxidant agents such as ROS, and decrease of available nitric oxide (NO). In this study, we have demonstrated the effect of ascorbic acid as an antioxidant on nitric oxide metabolites and systolic blood pressure in rats exposed to low levels of lead.

Materials and Methods:

The adult male Wistar rats weighing 200-250 g were divided into four groups: control, lead acetate (receiving 100 ppm lead acetate in drinking water), lead acetate plus ascorbic acid (receiving 100 ppm lead acetate and 1 g/l ascorbic acid in drinking water), and ascorbic acid (receiving 1 g/l ascorbic acid in drinking water) groups. The animals were anesthetized with ketamin/xylazine (50 and 7 mg/kg, respectively, ip) and systolic blood pressure was then measured from the tail of the animals by a sphygmomanometer. Nitric oxide levels in serum were measured indirectly by evaluation of its stable metabolites (total nitrite and nitrate (NOχ)).

Results:

After 8 and 12 weeks, systolic blood pressure in the lead acetate group was significantly elevated compared to the control group. Ascorbic acid supplementation could prevent the systolic blood pressure rise in the lead acetate plus ascorbic acid group and there was no significant difference relative to the control group. The serum NOχ levels in lead acetate group significantly decreased in relation to the control group, but this reduction was not significantly different between the lead acetate plus ascorbic acid group and the control group.

Conclusion:

Results of this study suggest that ascorbic acid as an antioxidant prevents the lead induced hypertension. This effect may be mediated by inhibition of NOχ oxidation and thereby increasing availability of NO.     

Effect of atorvastatin and hydroxychloroquine combination on blood glucose in alloxan-induced diabetic rats

Objective:

To evaluate the antihyperglycemic activity of atorvastatin and hydroxychloroquine combination in alloxan-induced diabetic rats.

Materials and Methods:

Alloxan induced diabetic Wistar male rats were randomized into six groups of 6 rats each. (Normal rats, diabetic control, atorvastatin (ATV), hydroxychloroquine (HCQ), ATV 5 mg /kg + HCQ 100 mg/kg, and ATV 10 mg/kg + HCQ 200 mg/kg). The rats were treated for 9 days and blood samples were collected at baseline and end of therapy. These samples were analyzed for plasma glucose by autoanalyzer. Changes in body weight, water, food intakes and total protein content were also recorded.

Results:

Atorvastatin and hydroxychloroquine alone and in combination reported significant fall in blood glucose level from baseline. Fall in glucose level was significantly more in high dose combination of atorvastatin and hydroxychloroquine (ATV: 10 mg/kg + HCQ: 200 mg/kg) as compared to other study treatment groups (ATV: 17% Vs HCQ: 7% Vs ATV 5mg/kg + HCQ 100mg /kg: 14% Vs ATV 10mg/kg + HCQ 200mg /kg: 21%; p<0.01). ATV and HCQ individually and in combination also improved the body weight loss. The weight gain was significantly more in combination treated rats as compared to positive control group and greater than those who received atorvastatin and hydroxychloroquine alone. Rats treated with the combination also reported significant decrease in food intake and significant increase in total protein.

Conclusion:

Increased hypoglycemic effect in combination may be due to potentiation or synergism between HCQ and ATV. Further studies are required to demonstrate clinically significant antidiabetic effect.     

阿托伐他汀和氯沙坦联合用药对老年单纯收缩期高血压患者脉压的影响

目的观察阿托伐他汀和氯沙坦联合用药对老年单纯收缩期高血压(ISH)患者脉压(PP)的影响。方法将62例老年ISH患者随机分为2组,对照组30例用氯沙坦片(50mg·d~(-1),po),治疗组32例用氯沙坦片(50mg·d~(-1),po)加阿托伐他汀片(20mg·d~(-1),po),观察12wk,每2周随访血压1次并记录。结果在治疗wk 12时,对照组PP从治疗前(74.67±7.77)mm Hg降至(67.37±5.53)mm Hg;治疗组PP从治疗前(75.06±6.96)mm Hg降至(59.75±5.92)mm Hg。治疗后2组PP之间差异有高度统计学意义(t=5.255,P<0.01)。结论阿托伐他汀和氯沙坦联合用药有助于改善老年ISH患者的PP。     

Effect of ketanserin on blood pressure in rats

Ketanserin, a selective serotonergic (5-HT2) antagonist, also has affinity for alpha 1-adrenoceptors. It is not clear whether the hypotensive mechanism of ketanserin is due to its antagonistic action to 5-HT2 receptor or to its affinity for alpha 1 adrenoceptors. The hypotensive mechanism of ketanserin was studied in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anesthetized rats were used (alpha-chloralose + urethane, i.p.). Up to 3 ml of blood was drawn from each rat for analysis. Plasma norepinephrine (NE) was determined by radioenzymatic assay. Plasma serotonin (5-HT) was determined by HPLC-ECD. Adrenal nerve discharges were counted by a digital pulse counter. Ketanserin (0.5 mg/kg, 5.0 mg/kg, i.v.) produced a dose-dependent reduction of mean arterial pressure (MAP) in both SHRSP and WKY. MAP of SHRSP decreased significantly as compared with WKY. Both plasma NE and 5-HT showed a tendency to increase during ketanserin administration (5.0 mg/kg, i.v.). Ketanserin significantly antagonized the BP response induced by exogenously injected 5-HT (30 micrograms/kg) and NE (10 micrograms/kg). Adrenal nerve activity was reduced in parallel with the decrease in BP and HR. These findings suggest that ketanserin produced a decrease in BP via both peripheral and central action in rats.     

Vasodilatation induced by sinomenine lowers blood pressure in spontaneously hypertensive rats

1. Sinomenine is an alkaloid with a wide range of pharmacological actions. In the present study, we investigated the effect of sinomenine on blood pressure and its possible mechanisms of action. 2. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were given intraperitoneal injections of sinomenine. At 30 min, 2.5-10 mg/kg sinomenine decreased systolic blood pressure (SBP) in a dose-dependent manner in SHR, but had no effect on the SBP in WKY rats. 3. The vascular effect of sinomenine was then examined in aortic rings isolated from Wistar rats. Sinomenine (0.1-10 micromol/L) produced concentration-dependent relaxation in aortic rings precontracted with phenylephrine (10 nmol/L) or KCl (40 mmol/L). Glibenclamide (1-100 micromol/L), a specific inhibitor of ATP-sensitive K(+) channels attenuated the sinomenine-induced relaxation, but this effect was not observed when inhibitors of other types of K(+) channels were used. 4. We further investigated the effects of sinomenine on changes in intracellular Ca(2+) concentrations ([Ca(2+)](i)) in cultured aortic smooth muscle (A7r5) cells by using the Ca(2+)-sensitive dye fura-2 as an indicator. Sinomenine, over the concentration range 0.1-10 micromol/L, decreased the increases in [Ca(2+)](i) elicited by phenylephrine (1 micromol/L) or KCl (40 mmol/L) in a concentration-dependent manner. Glibenclamide (1-100 micromol/L) abolished the effects of sinomenine. 5. In conclusion, sinomenine causes vascular relaxation by opening ATP-sensitive K(+) channels, thus decreasing [Ca(2+)](i).