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维格列汀与替米沙坦联合治疗实验性2型糖尿病大鼠糖尿病肾病

Dual therapy of vildagliptin and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats.

作者信息

Sharma Ashish Kumar, Kanawat Devendra Singh, Mishra Akanksha, Dhakad Prashant Kumar, Sharma Prashant, Srivastava Varnika, Joshi Sneha, Joshi Megha, Raikwar Sachin Kumar, Kurmi Muneem Kumar, Srinivasan Bharthu Parthsarthi

机构信息

Department of Pharmacology, Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, India

Department of Pharmacology, Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, India.

出版信息

J Renin Angiotensin Aldosterone Syst. 2014 Dec;15(4):410-8. doi: 10.1177/1470320313475908. Epub 2013 Feb 8.

Abstract

INTRODUCTION

The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats.

MATERIALS AND METHODS

In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed.

RESULTS

Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats.

CONCLUSIONS

The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin-angiotensin system.

摘要

引言

本文的目的是研究替米沙坦与维格列汀联合治疗与维格列汀和替米沙坦单药治疗对2型糖尿病大鼠糖尿病肾病的影响。

材料与方法

给成年大鼠腹腔注射链脲佐菌素(65mg/kg)和烟酰胺(110mg/kg)以诱导糖尿病肾病。将雌雄大鼠随机分为以下几组:(i)三联疗法:二甲双胍(120mg/kg,口服)+吡格列酮(1.25mg/kg,口服)+格列美脲(0.7mg/kg,口服);(ii)双联疗法:维格列汀(8.76mg/kg,口服)+替米沙坦(6.48mg/kg,口服);(iii)维格列汀(8.76mg/kg,口服);(iv)替米沙坦(6.48mg/kg,口服);口服给药35天。在第7、14、21、28和35天每周测量血压、血糖水平、体重、血清肌酐水平、尿蛋白白蛋白水平和血尿素氮(BUN)。观察肾脏结构变化。

结果

与正常对照大鼠相比,糖尿病大鼠的血压、血糖水平、血清肌酐水平、尿蛋白白蛋白水平、BUN和肾脏恶化程度显著增加。维格列汀+替米沙坦治疗组在糖尿病神经病变大鼠中未出现体重增加,且血压、肾血管结构和生化参数得到控制。

结论

与单药治疗相比,维格列汀联合替米沙坦对血压、血糖和糖尿病肾病标志物的控制效果最佳,可改善肾脏结构变化和肾功能,这可能是由于对肾素-血管紧张素系统的双重抑制作用。

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