替米沙坦联合阿托伐他汀治疗糖尿病肾病的疗效分析

目的:探讨替米坦联合阿托伐他汀治疗糖尿病肾病(DN)的疗效及机制.方法:选择糖尿病肾病60例,随机分为治疗组和对照组各30例,对照组单用替米沙坦治疗,治疗组应用替米沙坦联合阿托伐他汀治疗,疗程6个月.治疗前后观察TC、TG、尿微量白蛋白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6的值.结果:治疗前,两组TC、TG、尿微量白蛋白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6的值比较无明显差异(P>0.05),治疗6月后,与治疗前比较,除TC、TG外,两组患者的尿微量白蛋 白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6的值下降(P<0.01),治疗组的TC、TG、尿微量白蛋白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6值较对照组低,差异有统计学意义(P<0.01).结论:采用替米沙坦和阿托伐他汀治疗糖尿病肾病具有降血脂、减少尿蛋白、改善肾功能、延缓病情进展的作用.     

阿托伐他汀联合厄贝沙坦对老年早期糖尿病肾病患者肾功能及微炎症状态的影响

目的:探讨阿托伐他汀联合厄贝沙坦对老年早期糖尿病肾病(DN)患者肾功能及微炎症状态的影响。方法:选取2016年4月到2017年2月在我院肾内科接受治疗的老年早期DN患者84例,根据随机数字表法将患者分为对照组和观察组,各42例。对照组给予厄贝沙坦进行治疗,观察组给予阿托伐他汀联合厄贝沙坦进行治疗。比较两组患者的尿微量白蛋白排泄率(UAER)及两组患者血肌酐(Scr)、血尿素氮(BUN)、β2微球蛋白(β2-MG)、白细胞介素-1(IL-1)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平,并比较两组患者治疗过程中出现的不良反应。结果:治疗后两组患者的UAER、Scr、BUN、β2-MG水平均降低,且观察组的UAER、Scr、BUN、β2-MG均低于对照组(P0.05)。治疗后两组患者血清中IL-1、TNF-α水平均降低,IL-10水平升高(P0.05);治疗后观察组血清中IL-1、TNF-α水平低于对照组,IL-10水平高于对照组(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。结论:阿托伐他汀联合厄贝沙坦对老年早期DN患者有较好的治疗效果,可显著改善患者的肾功能,减轻微炎症状态,且安全性较好,值得临床推广应用。     

氟伐他汀对慢性心力衰竭患者心功能及预后的影响

目的:探讨氟伐他汀对慢性心力衰竭患者心功能及预后的影响.方法:采用回顾性分析的方法,分析我院收治的120例慢性心力衰竭患者的临床资料,依据治疗方式不同分为观察组和对照组.结果:观察组患者治疗后生命体征、彩超结果及心电图结果均明显优于对照组,P＜0.05,差异均有统计学意义.结论:氟伐他汀治疗心力衰竭患者临床疗效明显,值得临床推广应用.     

不同剂量氟伐他汀对冠心病伴血脂增高患者的临床作用研究

目的:观察不同剂量氟伐他汀对冠心病伴血脂增高患者的临床效果及安全性,为临床治疗提供依据。方法:选择我院2010年5月~2013年2月收治的96例冠心病伴高脂血症患者并将其进行随机分组,即20 mg及40 mg氟伐他汀治疗组各48例,观察和比较两组的临床疗效及不良反应的发生情况。结果:经4周、8周治疗后,两组患者的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)的水平均较同组治疗前显著降低,差异均具有统计学意义(P0.05);高密度脂蛋白胆固醇(HDL-C)均较同组治疗前明显升高,差异有统计学意义(P0.05);40 mg组hs-CRP含量下降,较20mg组显著,差异明显具有统计学意义(P0.05)。结论:对于冠心病伴血脂增高患者,采用高剂量氟伐他汀进行降脂治疗临床疗效较好,且安全性高,建议推广应用。     

高效液相色谱法测定氟伐他汀钠缓释片的含量

建立高效液相色谱法测定含量和含量均匀度的方法。采用SHIMADZU CLC-ODS色谱柱,以乙睛-水-冰醋酸(380∶120∶0.2)为流动相,234nm波长处检测。氟伐他汀钠在41μg/mL~328μg/mL浓度范围内线性关系良好(r=0.9998),平均回收率为100.5%,相对标准偏差(relative standaral deviation,RSD)0.5%(n=9)。本方法具有简单,柱效高,经济等优点。     

阿托伐他汀治疗阿尔茨海默病疗效观察

目的：研究他汀类药物在改善阿尔茨海默病患者认知功能障碍的作用。方法：将阿尔茨海默痛患者40例,随机分成治疗组（阿托伐他汀钙20mg1次／d口服）和对照组（茴拉西坦0．2g3次／天口服）,连续用药90d,在30d、60d、90d分别对两组病人进行认知功能评分（简易精神量表）。结果：利用t检验的方法计算t值,30d比较,t=-0．938（P〉0．05,差异无统计学意义）;60d比较,t=1．333（P〉0．05,差异无统计学意义）;90d比较t=2．356（P〈0．05,差异具有统计学意义）,提示90天后治疗组改善认知功能障碍优于对照组,且随着用药时间的延长,优势显现可能越为明显。结论：阿托伐他汀可能有助于阿尔茨海默病的治疗。     

瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的：观察他汀类调脂药物瑞舒伐他汀（Rosuvastatin）对2型糖尿病（type2diabetesmellitus,T2DM）大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法：将45只雄性SD大鼠随机分为正常对照组（NC组）、2型糖尿病组（DM组）、2型糖尿病瑞舒伐他汀治疗组（DR组）,每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/（kg.d）灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）水平与稳态血糖（BG）、稳态胰岛素（PGI）浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40（clusterofdifferentiation 40,CD40）及基质金属蛋白酶-2（MMP-2）、激活蛋白-1（activator protein-1,AP-1）的表达水平。结果：DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高（F=33.71~426.05,q=5.26~40.82,P〈0.01）,但2组间各指标比较差异无显著性（P〉0.05）。DR组CD40、MMP-2、AP-1表达水平和浸润的单核细胞数明显低于DM组（F=36.86~716.82,q=8.59~37.86,P〈0.05）,DR组主动脉内皮损伤明显轻于DM组。结论：瑞舒伐他汀能抑制CD40、MMP-2、AP-1表达和单核细胞浸润,防止早期AS形成。     

瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的:观察他汀类调脂药物瑞舒伐他汀(Rosuvastatin)对2型糖尿病(type2diabetesmellitus,T2DM)大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法:将45只雄性SD大鼠随机分为正常对照组(NC组)、2型糖尿病组(DM组)、2型糖尿病瑞舒伐他汀治疗组(DR组),每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/(kg.d)灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平与稳态血糖(BG)、稳态胰岛素(PGI)浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40(clusterofdifferentiation 40,CD40)及基质金属蛋白酶-2(MMP-2)、激活蛋白-1(activator protein-1,AP-1)的表达水平。结果:DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高(F=33.71~426....     

匹伐他汀临床应用的最新进展

匹伐他汀(pitavastatin)是新一代人工合成的降血脂类药物。该药是新一代HMG-COA还原酶抑制剂,用于治疗原发型高脂血症和混合型血脂障碍,能够显著降低LDL、TC、TG、及升高HDL-C。药物动力学性质优良,具有肝细胞选择性,并且毒性低,安全性好,具有抗动脉粥样硬化、促进血管生成和抗炎作用。本文就匹伐他汀的临床研究进展进行综述。     

川芎嗪联合阿托伐他汀治疗肺动脉高压的临床疗效分析

目的:观察川芎嗪联合阿托伐他汀治疗肺动脉高压的临床疗效及安全性。方法:将96例肺动脉高压患者随机分成两组,其中治疗组48人,对照组48人。治疗组患者在常规治疗基础上采川芎嗪联合阿托伐他汀治疗,对照组患者在常规治疗基础上单采用阿托伐他汀治疗,通过检测平均动脉压(mAP)、平均肺动脉压(mPAP)、肺血管阻力(PVR)、心脏指数(CI)、左心室射血分数(LVER)、Borg呼吸困难指数(Borg dyspnea)、6分钟步行距离(6TWD)以及肺功能升级(WHO FC)等指标评价其疗效。结果:两组患者经过6个月的治疗后,mPAP、PVR与治疗前相比显著降低,而CI、LVEF和6MWD均显著升高,差异均有统计学意义(P<0.05),治疗前后两组mAP与Borg呼吸困难指数均没有统计学差异(P>0.05),治疗组的mAP、LVEF以及6TWD与对照组相比差异有统计学意义(P<0.05)。结论:川芎嗪联合阿托伐他汀治疗充肺动脉高压临床疗效优于单纯应用阿托伐他汀。     

Cardiovascular disease in patients with diabetic nephropathy

Diabetic nephropathy, which represents a major form of chronic kidney disease (CKD), is a leading cause of end-stage renal disease worldwide, and is also a risk factor for cardiovascular disease (CVD). Patients with diabetes and CKD have poorer outcomes after myocardial infarction. The underlying pathogenic mechanism that links diabetic nephropathy to a high risk of CVD remains unclear. In addition to traditional risk factors, including hypertension, hyperglycemia, and dyslipidemia, identification of novel modifiable risk factors is important in preventing CVD in people with diabetes. Inflammation/oxidative stress are known to be associated with an increased risk for CVD in patients with diabetic nephropathy. Moreover, homocysteine, advanced glycation end products, asymmetric dimethylarginine, and anemia may play a role in the development and progression of atherosclerosis in patients with diabetic nephropathy. This review summarizes the epidemiologic evidence, molecular mechanisms responsible for the increased risk for CVD in patients with diabetic nephropathy, and therapeutic intervention for diabetic nephropathy as evidenced by large-scale clinical trials.     

Clinical significance of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy

Objective

To investigate the levels of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy at different stages.

Methods

A total of 80 patients with type 2 diabetes mellitus were enrolled in the present study. According to 24 h urinary albumin excretion ratio and renal function, they were further divided into group of diabetes without microalbuminuria (DN0, n = 20), microalbuminuria group (DN1, n = 20), macroalbuminuria group (DN2, n = 20) and renal insufficiency group (DN3, n = 20). Another 20 healthy subjects were enrolled as control group (non-DM). Plasma CD146 and P-selectin were measured by ELISA.

Results

Plasma CD146 and P-selectin were significantly increased in patients with type 2 diabetes with microalbuminuria (DN1) compared with health control (CD146: 415.3 ± 29.0 vs. 243.5 ± 14.7 ng/ml, P < 0.05; P-selectin: 66.8 ± 3.4 vs. 45.3 ± 2.7 ng/ml, P < 0.001). With the development of diabetic nephropathy, both plasma CD146 and P-selectin level progressively rise, with the highest levels in patients with significant renal insufficiency (DN3: 515.9 ± 36.9 and 81.5 ± 5.1 ng/ml respectively, P < 0.001). Moreover, the increase in CD146 is positively co-related to the rise of P-selectin in patients with type 2 diabetes.

Conclusion

Expression of CD146 and P-selectin in patients with type 2 diabetes is elevated, and they are positively correlated with severity of diabetic nephropathy.     

Clinical examination of diabetic patients treated with monocomponent insulin manufactured by MP Polfa

An effect of replacing conventional forms of insulin by the monocomponent insulin manufactured by "Polfa" was studied in the group of 22 diabetics. The patients were followed up for 12 months. An effect of monocomponent insulin on daily requirement of insulin, levels of anti-insulin, monocomponent and pancreatic peptide antibodies, compensation of diabetes mellitus, and lipodystrophy were investigated. New insulin preparation decreased anti-insulin and pancreatic peptide antibodies level and markedly diminished lipodystrophy. However, daily insulin requirement, degree of diabetes mellitus compensation, and anti-proinsulin antibodies level remained unchanged.     

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy.

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks'' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.     

Plasma proteome analysis of patients with type 1 diabetes with diabetic nephropathy

Background  

As part of a clinical proteomics program focused on diabetes and its complications we are looking for new and better protein biomarkers for diabetic nephropathy. The search for new and better biomarkers for diabetic nephropathy has, with a few exceptions, previously focused on either hypothesis-driven studies or urinary based investigations. To date only two studies have investigated the proteome of blood in search for new biomarkers, and these studies were conducted in sera from patients with type 2 diabetes. This is the first reported in depth proteomic study where plasma from type 1 diabetic patients was investigated with the goal of finding improved candidate biomarkers to predict diabetic nephropathy. In order to reach lower concentration proteins in plasma a pre-fractionation step, either hexapeptide bead-based libraries or anion exchange chromatography, was performed prior to surface enhanced laser desorption/ionization time-of-flight mass spectrometry analysis.     

Increased serum levels of interleukin-18 in patients with diabetic nephropathy

In the present study we measured interleukin-18 (IL-18) and tumour necrosis factor-alpha (TNF-alpha) levels by enzyme linked immunosorbent assay (ELISA) in sera from 65 diabetic [30 with type 1 insulin dependent diabetes mellitus (IDDM) and 35 with type 2 non-insulin dependent diabetes mellitus (NIDDM)] patients and 15 healthy volunteers, to investigate their associations with metabolic parameters and to elucidate their roles in the pathogenesis of diabetic complications especially diabetic nephropathy. Levels of IL-18 and TNF-alpha were significantly higher in both IDDM and NIDDM individuals as compared to the control group. Similarly, their levels in patients with diabetic nephropathy increased gradually according to the clinical stage of the disease, being highest in macroalbuminuric stage. Correlation analyses showed that the serum IL-18 and TNF-alpha concentration were positively correlated with each other and positively with fasting plasma glucose (FPG), 2h postprandial glucose, glycosylated hemoglobin (HbA1c), triglyceride, and urinary albumin levels and negative correlation between TNF-alpha and high density lipoprotein cholesterol (HDL-C) were also found in diabetic subjects. High serum levels of IL-18 and TNF-alpha suggested that they might play a role in the pathogenesis of DM and in the development of nephropathy in diabetic patients whether of type 1 or 2.     

Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy

Adiponectin, a novel adipose-derived adipocytokine, has beneficial effects not only on improvement of insulin sensitivity but also on mitigation of vascular damage. To evaluate whether adiponectin is implicated in the pathogenesis of diabetic nephropathy characterized by microvascular damage, we examined urinary and serum adiponectin levels in type 2 diabetic patients with different stages of nephropathy. We first confirmed adiponectin is excreted into urine through Western blot analysis, followed by measurements of urinary and serum adiponectin levels by radioimmunoassay. Interestingly, urinary adiponectin excretion levels were markedly increased in patient group with overt nephropathy relative to the groups without nephropathy and with incipient nephropathy. Surprisingly, serum adiponectin levels were also elevated in patient group with overt nephropathy. Increased urinary adiponectin excretion may result from elevations in circulating adiponectin levels and enhanced filtration of circulating adiponectin through the damaged kidney. Furthermore, adiponectin synthesis in adipose tissue and its secretion into circulating blood may be enhanced to mitigate microvascular damage in the advanced stage of diabetic nephropathy.     

Gene polymorphisms in patients with type 2 diabetes and diabetic nephropathy

A considerable variability in the incidence and prevalence of diabetic nephropathy (DN) coheres with an important contribution of multigenetic predisposition in the development of DN. Some genes, which probably participate in the pathogenesis of diabetic nephropathy, also play a role in the regulation of blood pressure, familial hyperlipidemia, familial hypertension and other diseases of the cardiovascular system. We have examined the association of diabetic nephropathy, nephropathy of non-diabetic origin, hypertension and of type 2 diabetes itself with several genetic polymorphisms (the insertion/deletion polymorphism in the gene for angiotensin-converting enzyme, the G/T polymorphism in the glucose transporter 1 gene, the G/T (894) polymorphism and the T/C (−786) polymorphism in the eNOS gene in three groups of patients with diabetes mellitus: 1) patients without diabetic nephropathy (DM); 2) patients with DN; 3) patients with nephropathy of non-diabetic origin (NDRD). Angiotensin-converting enzyme is an important factor in a development of arterial hypertension, but in our groups of Central European diabetic patients the I/D polymorphism was not associated with diabetic nephropathy. Furthermore, we have confirmed that the T/C (T786C) polymorphism in the eNOS gene is associated with metabolic syndrome including type 2 diabetes.