Irbesartan attenuates renal injury with diabetic nephropathy rats

Abstract

Abstract: Objective To observe the effect of Irbesartan on renal injury in diabetic nephropathy (DN) rats. Methods The rats were randomly divided into control group, DN model group and Irbesartan treatment group. At the age of 22 weeks, body weight, random blood sugar, serum creatinine,urea nitrogen,and 24-hour urinary microalbumin were measured.The morphological changes of kidneys were observed. The expression of microRNA-192 in rat kidney was detected by fluorescence quantitative PCR,the expression of TGF-beta 1, Zeb1 and collagen Ⅰ in rat kidney were detected by Western blot and immuno-histochemistry. Results Compared with the control group, the body weight, random blood sugar, serum creatinine,urea nitrogen,and 24-hour urinary micro-albumin of the model group rats increased significantly (P＜ 0.05); Compared with the DN group, the body weight, random blood sugar, serum creatinine,urea nitrogen,and 24-hour urinary micro-albumin of the Irbesartan treatment group rats decreased significantly(P＜0.05). Irbesartan treatment can improve the general condition and renal pathological damage of DN rats. Compared with the normal control group, the expression of microRNA-192 in the kidney of DN rats in the DN model group was down-regulated (P＜0.05), while that in the Irbesartan group was up-regulated (P＜0.05). WB and immuno-histochemical results showed that the expression of TGF-beta 1, ZEB1 and collagen Ⅰ protein in kidney tissue of DN model group was significantly increased as compared with that of normal group (P＜0.05); Compared with DN group, Irbesartan treatment reduced expression of TGF-beta 1, ZEB1 and collagen Ⅰ protein, with statistical significance (P＜ 0.05). Conclusions Irbesartan attenuates renal damage in diabetic nephropathy rats.

Key words: diabetic nephropathy, miR-192, Irbesartan

CLC Number:

ZHANG Ya, HUANG Wen-hui, HOU Zhi-min, LIU Ju-xiang, LIU Jing. Irbesartan attenuates renal injury with diabetic nephropathy rats[J]. Basic & Clinical Medicine, 2020, 40(4): 506-511.

References

[1] Menke A, Casagrande S, Geiss L, et al. Prevalence of and trends in diabetes among adults in the United States, 1988—2012[J]. JAMA, 2015,314:1021-1029.
[2] 曹晔, 杨丹, 苏津,等. 糖尿病肾病患者肾素-血管紧张素-醛固酮系统与血流动力学的关系[J]. 临床检验杂志, 2012,30:1004-1005.
[3] 刘红, 韩璐璐, 谢爽,等. 连续口服厄贝沙坦对健康中国志愿者血浆microRNAs表达的影响[C].中国心脏大会, 2011:248-250.
[4]Kantharidis P, Wang B, Carew RM, et al. Diabetes complications: the microRNA perspective[J]. Diabetes, 2011, 60: 1832-1837.
[5]Lan HY, Chung AC. TGF-β/Smad signaling in kidney disease[J]. Semin Nephrol, 2012, 32: 236-243.
[6]Chung AC, Dong Y, Yang W, et al. Smad7 suppresses renal fibrosis via altering expression of TGF-β/Smad3-regulated microRNAs[J]. Mol Ther, 2013, 21: 388-398.
[7]Kriegel AJ, Liu Y, Cohen B, et al. miR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis[J]. Physiol Genomics, 2012, 44: 259-267.
[8]房勃龙, 韩鸿玲. TGF-β、Smad信号通路蛋白及α-SMA在糖尿病肾病患者肾组织中的表达和意义[J]. 天津医药, 2013,11:1067-1069.
[9]Kantharidis P, Wang B, Carew RM, et al. Diabetes complications: the microRNA perspective[J]. Diabetes, 2011, 60:1832-1837.
[10]Krupa A,Jenkins R,Luo DD,et al.Loss of microRNA-192promotes fibrogenesisindiabetic nephropathy[J].J Am Soc Nephrol,2010,21:438-447.
[11]Kriegel AJ,Fang Y,Liu Y,et al.microRNA-target pairs in human renal epithelial cells treated with transforming growth factor beta 1:a novel role of miR-382[J].Nucleic Acids Res,2010,38:8338-8347.
[12]Putta S,Lanting L,Sun G,et al.Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy[J].J Am Soc Nephrol,2012,23:458-469.
[13]Zhong X,Chung AC,Chen HY,et al.Smad3-mediated upregulation of miR-21 promotes renalfibrosis[J].J Am Soc Nephrol,2011,22:1668-1681.
[14]Kato M, Arce L, Wang M, et al. A microRNA circuit mediates transforming growth factor-β1 autoregulation in renal glomerular mesangial cells[J]. Kidney Int, 2011, 80: 358-368.
[15]Lv C, Zhou Y, Wu C, et al. The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy[J]. Diabetes Metab Res, 2015, 31: 717-724.