厄贝沙坦与黄葵胶囊对糖尿病肾病患者血清胱抑素C和β_2-微球蛋白的影响

目的:探讨厄贝沙坦联合黄葵胶囊对糖尿病肾病患者血清胱抑素C(CysC)和β_2-微球蛋白的影响。方法:将糖尿病肾病患者120例随机分为试验组和对照组各60例。对照组行常规降血糖方案治疗,试验组患者在对照组治疗的基础上口服厄贝沙坦联合黄葵胶囊治疗,连续治疗2个月。对患者治疗前后血肌酐(Scr)、尿素氮(BUN)、24小时尿蛋白定量、CysC、β_2-微球蛋白等指标进行观察。结果:试验组总有效率(86.7%)高于对照组(53.3%),差异具有统计学意义(χ2=30.86,P=0.000)。治疗前2组患者Scr、BUN、尿酸等肾功能指标以及CysC、β_2-微球蛋白等血清生化指标比较差异均无统计学意义(P0.05);治疗后2组患者Scr、BUN、尿酸等肾功能指标均有不同程度降低,试验组降低程度优于对照组,差异有统计学意义(P0.05)。2组患者CysC、β_2-微球蛋白等血清生化指标均有不同程度降低,且试验组低于对照组,差异具有统计学意义(P0.05)。结论:厄贝沙坦联合黄葵胶囊治疗糖尿病肾病疗效确切,能减少患者血清肌酐与尿蛋白浓度,能有效降低CysC和β_2-微球蛋白浓度,起到保护肾脏微血管作用。     

厄贝沙坦氢溴酸盐的毒理学和药效学研究

目的比较厄贝沙坦氢溴酸盐与厄贝沙坦的毒性和药效。方法采用无创血压测量比较了厄贝沙坦氢溴酸盐、厄贝沙坦对自发性高血压大鼠血压的影响。分别ip、ig给药,观察两种药物的半数致死量(LD50),对心率、呼吸以及动物自主活动的影响。结果自发性高血压大鼠的血压明显高于非自发性高血压大鼠,给予厄贝沙坦氢溴酸盐、厄贝沙坦后血压均降至正常水平,且两种药物的降压作用差异无显著性,但厄贝沙坦氢溴酸盐的药效持续时间更长。厄贝沙坦氢溴酸盐、厄贝沙坦对动物的呼吸、心率以及自主活动的影响无差异,但厄贝沙坦氢溴酸盐的LD50明显高于厄贝沙坦。结论厄贝沙坦氢溴酸盐具有和厄贝沙坦相同的降压作用,但是作用时间更长,安全性更高。     

PBPK modeling of irbesartan: incorporation of hepatic uptake

Physiological based pharmacokinetic (PBPK) modeling is now commonly used in drug development to integrate human or animal physiological data in order to predict pharmacokinetic profiles. The aim of this work was to construct and refine a PBPK model of irbesartan taking into account its active uptake via OATP1B1/B3 in order to predict more accurately its pharmacokinetic profile using Simcyp^®. The activity and expression of the human hepatocyte transporters OATP1B1 and OATP1B3 were studied. The relative activity factors (RAFs) for OATP1B1 and OATP1B3 transporters were calculated from intrinsic clearances obtained by concentration dependent uptake experiments in human hepatocytes and HEK overexpressing cells: RAF_1B1 using estrone‐3‐sulfate and pitavastatine clearances, and RAF_1B3 using cholecystokinine octapeptide (CCK‐8) clearances. The relative expression factor (REF) was calculated by comparing immunoblotting of hepatocytes (REF_HH) or tissues (REF_tissue) with those of overexpressing HEK cells for each transporter. These scaling factors were applied in a PBPK model of irbesartan using the Simcyp® simulator. Pharmacokinetic simulation using REF_HH (1.82 for OATP1B1, 8.03 for OATP1B3) as an extrapolation factor was the closest to the human clinical pharmacokinetic profile of irbesartan. These investigations show the importance of integrating the contribution of the active uptake of a drug in the liver to improve PBPK modeling. Copyright © 2015 John Wiley & Sons, Ltd.     

生脉注射液联合厄贝沙坦治疗冠心病慢性心力衰竭的疗效

目的研究生脉注射液联合厄贝沙坦治疗冠心病慢性心力衰竭的疗效。方法选取我院2017年3月—2018年3月收治的100例慢性心力衰竭患者,随机分为两组各50例。对照组患者口服厄贝沙坦片,1片/次,1次/d,治疗组患者在对照组基础上每日给予生脉注射液,将30 mL生脉注射液溶于250 mL 5%葡萄糖注射液中,两组患者均持续治疗30 d。对比两组临床疗效、心功能相关指标、IL-6、CRP和TNF-α水平、临床症状消失时间和不良反应发生率。结果治疗后治疗组治疗有效率较高(P<0.05);两组患者心输出量(cardiac output,CO)、心脏指数(cardiac index,CI)、有效循环血量(effective circulatory volume,ECV)和心肌耗氧量(myocardial oxygen consumption,MVO)水平均低于治疗前(P<0.05);并且治疗组降低程度较大(P<0.05);两组患者左室射血分数(left ventricular ejection fraction,LVEF)、左室舒张末期内径(left ventricular end-diastolic dimension,LVDd)、室间隔厚度(interventricular septal thickness,IVST)、左室后壁厚度(left ventricular posterior wall thickness,LVPWT)改善(P<0.05);并且治疗组改善程度较大(P<0.05);两组患者C反应蛋白(C-reactive protein,CRP)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白介素-6(Interleukin-6,IL-6)水平低于治疗前(P<0.05);并且治疗组降低程度较大(P<0.05)。结论慢性心力衰竭采用生脉注射液联合厄贝沙坦进行治疗,具有较好的临床疗效。     

真武汤联合厄贝沙坦、美托洛尔治疗心肾综合征患者的临床效果

目的研究真武汤联合厄贝沙坦、美托洛尔治疗心肾综合征患者的临床效果。方法选取2016年5月至2019年5月我院收治的100例心肾综合征患者为研究对象,根据入院顺序随机将其分为对照组与观察组,各50例。对照组给予厄贝沙坦、美托洛尔治疗,观察组在对照组基础上给予真武汤治疗。比较两组的临床疗效。结果治疗后,两组患者的Scr、BUN、BNP水平均降低,且观察组低于对照组(P<0.05)。观察组的治疗总有效率高于对照组(P<0.05)。治疗后,两组的CRP、IL-18、TNF-α水平均降低,且观察组低于对照组(P<0.05)。治疗后,两组的ET-1水平均降低,NO水平均升高,观察组优于对照组(P<0.05)。结论真武汤联合厄贝沙坦、美托洛尔治疗心肾综合征患者具有显著的协同作用,且能够降低患者的血清炎症因子水平,值得临床推广应用。     

What is the impact of PRIME on real‐life diabetic nephropathy?

Type 2 diabetes is increasing globally and is a major cause of conditions such as cardiovascular disease, retinopathy and nephropathy. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study demonstrated that the progression of renal disease could be slowed by tight glycaemic control and treating any associated hypertension with angiotensin-converting enzyme inhibition. Recent clinical trials have supported the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, resulting in the approval of new therapeutic indications in the United States and Europe. The objective of this review is to demonstrate how results from the Program for Irbesartan Mortality and morbidity Evaluation studies apply to clinical practice, and to show how the benefits of irbesartan therapy can be realised at any stage of renal disease in patients with diabetes.     

Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T₁ (AT₁) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.     

伊贝沙坦对急性心肌梗死后左室功能及重塑的影响

目的 :观察伊贝沙坦对急性心肌梗死 (AMI)后左室重塑的阻抑作用。方法 :将 72例 AMI患者随机分为常规治疗组 36例、伊贝沙坦治疗组 36例 ,并于 AMI后 2、2 4周分别进行超声心动图和平衡法核素心室造影 ,测定左室心肌质量、左室收缩功能和舒张功能 ,了解伊贝沙坦对 AMI后左室重塑的阻抑作用。结果 :AMI后 2 4周时伊贝沙坦与常规治疗组比较室间隔厚度、左室后壁厚度、左室舒张末内径和左室心肌质量指数均明显降低 (P<0 .0 5或 P<0 .0 1)。AMI后 2 4周时 ,伊贝沙坦治疗组与对照组比较左室射血分数明显增加 (P<0 .0 5 ) ,左室高峰射血率明显升高 ,左室高峰射率时间显著下降 (P均 <0 .0 5 ) ,同时左室高峰充盈率明显升高(P<0 .0 1) ,左室高峰充盈率时间显著下降 (P<0 .0 1)。结论 :伊贝沙坦能明显减轻心肌梗死后心肌肥厚和左室重塑 ,改善左室功能。     

重组人脑利钠肽联合厄贝沙坦对心肌梗死PCI术后患者疗效及HCY、IMA、Lp-PLA2影响

目的 观察重组人脑利钠肽（recombinant human brain natriuretic peptide,rhBNP）联合厄贝沙坦对急性心肌梗死（acutemyocardial infarction,AMI）经皮冠状动脉介入术（percutaneous coronary intervention,PCI）后患者疗效及对同型半胱氨酸（homocysteine,Hcy）、缺血修饰白蛋白（ischemia modified albumin,IMA）、脂蛋白相关磷脂酶A （2 lipoprotein-associated phospholipase A2,Lp-PLA2）影响。方法 选取2015年1月—2017年12月150例行PCI术成功的AMI患者,随机分为观察组（75例）和对照组（75例）,对照组患者术后予常规药物治疗和静脉注射rhBNP72 h;观察组在此基础上给予口服厄贝沙坦150 mg·d^-1。观察2组患者临床疗效、心肌酶学改变、心功能指标及不良反应情况;观察2组患者Hcy、IMA、Lp-PLA2改变。结果 观察组治疗后的临床治疗总有效率（89.33%）显著高于对照组（65.33%）（P<0.05）。与治疗前相比,治疗后2组患者体内CK和CK-MB峰值明显降低,观察组患者明显低于对照组（P<0.05）。与对照组比较,治疗后,观察组左心室功能参数改善明显（P<0.05）;血清HCY、IMA、Lp-PLA2含量下降更为明显（P<0.05）;心源性死亡、心肌二次梗死、再发心绞痛、心力衰竭人数较少,但不具有统计学差异;不良反应总数明显较低（P<0.05）。结论 rhBNP联合厄贝沙坦对PCI术后的AMI患者心肌具有保护作用,明显改善患者预后,可明显降低患者体内HCY、IMA、Lp-PLA2水平。     

川芎嗪通过抑制PI3K/Akt/mTOR通路诱导自噬改善糖尿病肾病大鼠肾损害

目的 探讨川芎嗪对糖尿病肾病（DN）大鼠肾脏 PI3K/Akt/mTOR信号通路和自噬标志蛋白 LC3B表达以及 尿微量白蛋白与尿肌酐比值（UACR）、肾脏病理的影响。方法 采用链脲佐菌素建立 DN大鼠模型,将模型大鼠随机 分为模型组,川芎嗪低、中、高剂量组,厄贝沙坦组;另设正常组,每组 12只。分别干预 8周后,采用酶法测定尿肌酐, 免疫比浊法测定尿微量白蛋白,计算 UACR;取肾组织,经甲醛固定后,进行苏木精-伊红（HE）和过碘酸-雪夫（PAS） 染色;通过蛋白免疫印迹法（Western blot）和免疫组化检测大鼠肾组织 PI3K/Akt/mTOR信号通路以及自噬标志蛋白 LC3B 表达的变化。结果 川芎嗪能减缓 DN 大鼠 UACR 的升高,改善其肾脏病理变化,其中川芎嗪中、高剂量组 UACR显著低于模型组（P＜0.05）,且川芎嗪中、高剂量组与厄贝沙坦组间比较差异无统计学意义（P＞0.05）。此外, 川芎嗪能抑制 DN大鼠肾组织 p-PI3K、p-Akt、p-mTOR的表达,进而提高自噬标志蛋白 LC3B的表达水平和 LC3B-Ⅱ/ LC3B-Ⅰ比值。结论 川芎嗪能降低 DN大鼠 UACR的升高、改善其肾脏病理变化,发挥以上肾保护作用的机制可能 与其抑制 PI3K/Akt/mTOR信号通路,进而促进肾脏自噬有关。