Imidapril improves l-NAME-exacerbated nephrosclerosis with TGF-β1 inhibition in spontaneously hypertensive rats
Imidapril improves l-NAME-exacerbated nephrosclerosis with TGF-β1 inhibition in spontaneously hypertensive rats
复制标题
咪达普利通过抑制 TGF-β1 改善自发性高血压大鼠的 l-NAME 加剧的肾硬化
DOI：
10.1097/01.hjh.0000125458.28861.49
复制
发表时间：
2004
影响因子：
4.9
通讯作者：
H. Matsuoka
中科院分区：
文献类型：
--
作者：
H. Ono;Mayumi Saitoh;Y. Ono;Toshihiko Ishimitu;H. Matsuoka
目的探讨慢性血管紧张素转换酶（ACE）抑制对自发性高血压大鼠（SHR）高血压性肾小球损伤的保护作用，以及在长期应用左旋硝基精氨酸甲酯（l-NAME）抑制一氧化氮合酶（NOS）过程中对凋亡诱导因子caspase-3和转化生长因子β1（TGF-β1）mRNA水平和免疫组织化学表达的影响。方法和结果3周，我们研究了三组20周龄的雄性SHR：对照组，L-NAME组，L-NAME和ACE抑制剂咪达普利治疗组。L-NAME大鼠发生严重的高血压性肾硬化，血压显著升高，尿蛋白排泄和血清肌酐水平显著增加，肾小球硬化和肾小管间质改变更严重。L-NAME组大鼠肾组织TGF-β1 mRNA水平较对照组明显升高。与l-NAME/SHR相比，咪达普利可显著降低血压，抑制肾硬化，降低TGF-β1 mRNA水平。在组织学上，咪达普利可降低肾小球细胞凋亡指数、TUNEL法检测凋亡细胞的DNA片段，减少caspase-3活性和TGF-β1阳性细胞面积。结论咪达普利可能通过抑制TGF-β1的产生和细胞凋亡而减轻肾小球和小动脉的损伤，保护肾功能。
Objective This study was designed to investigate whether chronic angiotensin-converting enzyme (ACE) inhibition prevents hypertensive glomerular injury and inhibits increases in the mRNA levels and immunohistological expression of the apoptosis inducer caspase-3, and transforming growth factor (TGF)-β1 during prolonged nitric oxide synthase (NOS) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in spontaneously hypertensive rats (SHR). Methods and results For 3 weeks, we studied three groups of 20-week-old male SHR: a control group, a l-NAME group, and a group treated with l-NAME and the ACE inhibitor imidapril. l-NAME rats developed severe hypertensive nephrosclerosis with significantly elevated blood pressure, markedly increased urinary protein excretion and serum creatinine levels, and more severe glomerulosclerosis and tubulo-interstitial changes. Levels of TGF-β1 mRNA in the renal tissue was also significantly increased in l-NAME rats compared with control SHR. Addition of imidapril significantly lowered blood pressure, inhibited nephrosclerosis and attenuated the mRNA level of TGF-β1 in comparison with l-NAME/SHR. Histologically, the glomerular cell apoptosis labeling index, terminal doxynucleotidil transferase-mediated dUTP nick-end labeling of fragmented DNA (TUNEL) and active caspase-3, and TGF-β1 positive areas were also reduced by imidapril. Conclusion These data suggest that imidapril prevents glomerular and arteriolar damages and renal functions, through inhibiting both TGF-β1 production and apoptosis induction.
影响因子：
15.9
作者：
KAGAMI, S;BORDER, WA;NOBLE, NA
通讯作者：
NOBLE, NA
卡托普利诱导的转化生长因子-β1 血清水平降低与胰岛素依赖型糖尿病患者的长期肾脏保护作用相关。
DOI：
10.1016/s0272-6386(99)70037-5
发表时间：
1999
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Sharma,K;Eltayeb,BO;McGowan,TA;Dunn,SR;Alzahabi,B;Rohde,R;Ziyadeh,FN;Lewis,EJ
通讯作者：
Lewis,EJ
影响因子：
120.7
作者：
Wright, JT;Bakris, G;Rostand, SG
通讯作者：
Rostand, SG