The relationship between visfatin and HOMA-IR in hypertensive patients, and the effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients with insulin resistance

Objective

To investigate the correlation between serum visfatin and insulin resistance (IR) in non-diabetic essential hypertensive (EH) patients with and without IR, and to evaluate the effect of antihypertensive treatment on serum visfatin and IR in these patients.

Methods

A total of 81 non-diabetic EH patients, including 54 with IR and 27 without IR, were enrolled. After two weeks wash-out, patients with IR were randomly assigned to telmisartan (group T) or amlodipine (group A) for 6 months. Blood samples were taken before and after treatment for measurement of routine biochemical parameters, visfatin and insulin resistance (measured by HOMA-IR).

Results

Visfatin was independently correlated with HOMA-IR (r = 0.845, P = 0.000). After 6 months of treatment, both drugs lowered HOMA-IR, more significantly so in group T than group A (P = 0.010). Serum visfatin levels increased in group T but decreased in group A.

Conclusion

Serum visfatin levels were higher in non-diabetic EH patients with IR compared with those without IR. Visfatin is independently correlated with HOMA-IR. Telmisartan lowers HOMA-IR to a greater extent than amlodipine. Interestingly, serum visfatin increased with telmisartan yet decreased with amlodipine treatment.     

替米沙坦对糖尿病大鼠肾脏组织中内质网应激介导相关细胞凋亡的保护作用

探讨血管紧张素Ⅱ受体拮抗剂对糖尿病大鼠肾脏组织中内质网应激相关的细胞凋亡的影响.31只雄性SD大鼠分为正常对照组、糖尿病组、替米沙坦干预组.12周试验结束后测量大鼠体重、24h尿蛋白量,检测血糖、血胰岛素、血肌酐等.肾脏细胞凋亡用TUNEL法检测;肾脏细胞内质网应激信号通路分子糖调节蛋白78( GRP78)、caspase12和CHOP用免疫组化及实时定量PCR法检测.糖尿病组的血糖、24h尿蛋白量、血肌酐显著高于对照组(P＜0.05);体重和血胰岛素较对照组低(P＜0.05).替米沙坦干预组的24h尿蛋白量、血肌酐较糖尿病组明显减少(P＜0.05),凋亡指数也显著低于糖尿病组(P＜0.05).大鼠内质网应激信号通路分子GRP78、caspase12、CHOP蛋白及其mRNA的表达,糖尿病组显著高于对照组和替米沙坦干预组(P＜0.05).内质网应激参与了糖尿病大鼠肾脏细胞的凋亡,替米沙坦对内质网应激介导相关的肾脏细胞凋亡有保护作用.     

替米沙坦对代谢综合征患者血管内皮功能的影响

目的观察替米沙坦对代谢综合征患者血管内皮功能的影响。方法代谢综合征患者76例随机分为常规组和实验组,每组38例,同时选择健康体检者38例作为对照组。实验组在常规用药的基础上加服替米沙坦80mg/d,治疗3个月。检测三组患者治疗前后血糖、血脂代谢指标、血浆一氧化氮（NO）、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性,观察血压及血管内皮舒张功能变化。结果治疗后常规组和实验组的血压、空腹血糖均明显下降（P〈0.05）,但两组间的血压、空腹血糖相比差异无统计学意义（P〉0.05）;实验组的肱动脉血流介导的舒张内径（FMD）（P〈0.05）、NO含量明显升高（P〈0.01）,MDA含量下降、SOD活性升高（P〈0.05）。治疗后常规组FMD、NO及MDA含量、SOD活性均无明显变化（P〉0.05）,与实验组相比差异有统计学意义（P〈0.05）。结论替米沙坦可减轻代谢综合征患者胰岛素抵抗及氧化应激水平,增加一氧化氮含量,改善血管内皮功能。     

美卡素联合氢氯噻嗪治疗原发性高血压65例疗效观察

日的观察美卡素（替米沙坦）与氢氯噻嗪联合治疗原发性高血压的疗效．方法将65例轻、中度原发性高血压患者随机分两组,治疗组（35例）用美卡素80mg／d,氢氯噻嗪25mg／d,对照组（30例）用美卡素80m洲,两组治疗时间均为7周．结果（1）与治疗前相比,治疗组及对照组患者血压均有下降,但治疗组疗效更显著,总有效率达97．14％,而对照组总有效率为93．33％,两组间比较差异有统计学意义（P〈0．05）;（2）不良反应：治疗前后两组间血糖、血脂、尿酸等比较均无统计学意义（P〉0．05）．结论美卡素与氢氯噻嗪联合治疗原发性高血压病疗效显著,且安全性良好．     

替米沙坦对原发性高血压患者心率变异性及心率震荡的影响

目的探讨替米沙坦对原发性高血压(EH)患者心率变异性(HRV)和心率震荡(HRT)的影响。方法选取2015年1月～2018年6月就诊的50例轻中度EH患者(观察组),予以口服替米沙坦40 mg,1次/d,血压下降不理想者则增至80 mg,连用8周。另取同期健康体检者30例作为对照组。观察并比较观察组治疗前后与对照组收缩压和舒张压、HRV和HRT水平的差异。结果观察组治疗前收缩压和舒张压水平均高于对照组(P0.01)。治疗8周后,观察组收缩压和舒张压较前下降(P0.05)。观察组治疗前SDNN、SDANN、RMSSD和PNN50水平低于对照组(P0.05或P0.01)。治疗8周后,观察组SDNN、SDANN、RMSSD和PNN50水平较前上升(P0.05)。观察组治疗前TO水平高于对照组,TS水平低于对照组(P0.01)。治疗8周后,观察组TO水平均较前下降,TS水平较前上升(P0.01)。结论 EH患者存在心脏自主神经功能紊乱。替米沙坦治疗EH降压作用良好平稳,能显著改善患者HRV和HRT水平,调节心脏自主神经功能,从而改善患者的预后。     

Liquid chromatographic-tandem mass spectrometric method for the simultaneous quantitation of telmisartan and hydrochlorothiazide in human plasma

A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of telmisartan and hydrochlorothiazide in human plasma. Sample preparation involved liquid-liquid extraction with diethyl ether-dichloromethane (60:40, v/v). The analytes and internal standard, probenecid, were separated on a Venusil XBP-C(8) column using gradient elution with acetonitrile-10 mM ammonium acetate-formic acid at a flow rate of 1.2 mL/min. Detection was by electrospray negative ionization mass spectrometry using multiple reaction monitoring of the transitions at m/z 513.0-->469.4 for telmisartan, m/z 295.9-->268.9 for hydrochlorothiazide and m/z 283.9-->239.9 for probenecid. For both analytes, the method was linear in the range 1.00-600 ng/mL with intra- and inter-day precision (as relative standard deviation) 相似文献   

Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study

Background: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular repair. EPCs may be reduced in HIV-infected (HIV+) persons, contributing to cardiovascular disease (CVD). Telmisartan is an angiotensin receptor blocker that increases EPCs in HIV-uninfected adults.

Objective: To assess telmisartan’s effects on EPC number and immunophenotype in older HIV + adults at risk for CVD.

Methods: HIV + persons ≥50 years old with HIV-1 RNA < 50 copies/mL on suppressive antiretroviral therapy and ≥1 CVD risk factor participated in a prospective, open-label, pilot study of oral telmisartan 80 mg daily for 12 weeks. Using CD34 and CD133 as markers of early maturity and KDR as a marker of endothelial lineage commitment, EPCs were quantified via flow cytometry and defined as viable CD3^?/CD33^?/CD19^?/glycophorin^? cells of four immunophenotypes: CD133⁺/KDR⁺, CD34⁺/KDR⁺, CD34⁺/CD133⁺, or CD34⁺/KDR⁺/CD133⁺. The primary endpoint was a 12-week change in EPC subsets (NCT01578772).

Results: Seventeen participants (88% men, median age 60 years and peripheral CD4⁺ T lymphocyte count 625 cells/mm³) enrolled and completed the study. After 6 and 12 weeks of telmisartan, frequencies of all EPC immunophenotypes were higher than baseline (all p < 0.10 except week 12 CD133⁺/KDR⁺ EPC, p = 0.13). Participants with lower baseline EPC levels had the largest gains. Additionally, the percentage of CD34⁺ cells with endothelial commitment (KDR⁺) increased.

Conclusions: Our data suggest that telmisartan use is associated with an increase in circulating EPCs in older HIV + individuals with CVD risk factors. Further controlled studies are needed to assess whether EPC increases translate to a reduction in CVD risk in this population.     

慢性心衰采用美托洛尔联合贝那普利治疗的临床疗效分析

目的：探讨慢性心力衰竭采用美托洛尔联合贝那普利治疗临床疗效。方法方便选取2015年2月-2016年3月该院收治慢性心力衰竭患者80例为研究对象,采用随机分组表将患者分为研究组和对照组,对照组采用常规强心、利尿、扩血管方法治疗,研究组在对照组治疗基础上给予美托洛尔联合贝那普利治疗,比较两组患者治疗前后左室射血分数(LVEF)、心率、B型尿钠肽(BNP)水平及疗效。结果治疗前两组患者LVEF、心率、BNP水平比较差异无统计学意义(P>0.05);治疗后研究组患者LVEF水平高于对照组,心率、BNP水平低于对照组[(66.8±5.8)% vs (54.8±5.9)%,(73.5±5.4)次/min vs (86.4±6.1)次/min,(135.4±23.8)pg/mL vs (355.7±45.7)pg/mL,P<0.05]。研究组患者治疗总有效率(95.00%)显著高于对照组(77.50%),比较差异有统计学意义(P<0.05)。结论慢性心力衰竭采用美托洛尔联合贝那普利治疗可减轻心脏负荷和耗氧量,改善患者临床症状,提高治疗效果。     

替米沙坦对糖尿病心肌病大鼠心肌超微结构的影响及其作用机制

目的 探讨替米沙坦对糖尿病心肌病(DCM)大鼠心肌超微结构的影响及其可能作用机制.方法 30只健康雄性Wistar大鼠,随机分成空白组10只和糖尿病组20只,糖尿病组用链脲佐菌素腹腔注射诱导建立DCM模型,建模成功后随机分成对照组及治疗组各10只.治疗组给予替米沙坦(20 mg/kg)灌胃治疗,空白组和对照组给予相同体积的生理盐水灌胃.给药16周后,光镜和电镜下观察各组大鼠心肌病理改变,采用脱氧核苷酸末端转移酶介导的dUTP缺口末端标记法检测心肌细胞凋亡情况,免疫组化法检测心肌细胞B淋巴细胞瘤因子-2(Bcl-2)、半胱氨酸-天冬氨酸蛋白酶-3(Caspase-3)及转化生长因子β1(TGF-β1)的表达情况.结果 光镜下对照组心肌细胞排列紊乱,心肌细胞核出现融合、消失、间质纤维化等改变,电镜下对照组心肌线粒体肿胀、嵴断裂甚至空泡化,肌丝成分减少、断裂.与对照组相比,治疗组光镜下心肌病理改变减轻,电镜下心肌超微结构病理改变也减轻.与空白组相比,对照组左室指数明显升高、凋亡细胞增多、Bcl-2表达减少,Caspase-3的表达及TGF-β1的A值增加(P＜0.05);与对照组比较,治疗组左室指数及凋亡指数下降、Bcl-2表达增加,而Caspase-3及TGF-β1的表达减少(P＜0.05).结论 替米沙坦可以改善DCM大鼠心肌超微结构,延缓心室重构.     

反相高效液相色谱法测定人血浆中替米沙坦的浓度

目的　建立RP -HPLC法测定人血浆中替米沙坦浓度。方法　用AgilentZORBAX×ODS柱 (4 .6× 1 5 0mm ,5 μm) ,流动相为水 -乙腈 -三乙胺 (6 0∶4 0∶0 .1 ) ,荧光检测激发波长为 30 0nm ,发射波长为 380nm ,采用萘乙酸为内标。结果　替米沙坦保留时间为 9min左右 ,浓度线性范围 1 0～ 35 0 0 μg·L-1 。结论　该法准确、快速、简便 ,可用作人血浆中替米沙坦浓度测定方法