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姜黄素通过减少 MMP-2 和 MMP-9 来预防 l-NAME 诱导的高血压引起的肾脏损伤。

Curcumin Prevents Renal Damage of l-NAME Induced Hypertension in by Reducing MMP-2 and MMP-9.

机构信息

Food and Medicines Department, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil.

Faculty of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, São Paulo, Brazil.

出版信息

Cell Biochem Funct. 2024 Sep;42(7):e4119. doi: 10.1002/cbf.4119.

DOI:10.1002/cbf.4119
PMID:39244707
Abstract

In the present study, we investigated whether curcumin administration would interfere with the main renal features of l-NAME-induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l-NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l-NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l-NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP-2 activity, as well as MMP-9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP-2 activity, and reduced MMP-2, MMP-9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP-2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l-NAME-induced hypertension and renal glomerular alterations, inhibited MMP-2 and MMP-9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension-induced renal outcomes.

摘要

在本研究中,我们研究了姜黄素给药是否会干扰 l-NAME 诱导的高血压模型的主要肾脏特征。为此,我们进行了体外和体内实验,以评估炎症、氧化应激和金属蛋白酶 (MMPs) 表达/活性的肾脏指标。通过 l-NAME(70mg/kg/天)诱导高血压,来自对照和高血压组的 Wistar 大鼠分别用姜黄素(50 或 100mg/kg/天;灌胃)或载体处理 14 天。采集血液和肾脏以确定血清肌酐水平、组织学改变、氧化应激、MMPs 表达和活性以及 ED1 表达。l-NAME 增加了血压,但姜黄素治疗的两种剂量均降低了这些值。l-NAME 处理增加了肌酐水平、肾小球面积、鲍曼氏腔、肾脏 MMP-2 活性以及 MMP-9 和 ED1 的表达,并减少了肾小球的数量。姜黄素治疗可预防肌酐水平、MMP-2 活性的增加,并降低 MMP-2、MMP-9、ED1 和超氧化物水平,同时增加超氧化物歧化酶活性,并部分预防肾小球改变。此外,姜黄素在体外直接抑制 MMP-2 活性。因此,我们的主要发现表明,姜黄素降低了 l-NAME 诱导的高血压和肾脏肾小球改变,抑制了 MMP-2 和 MMP-9 的表达/活性,并减少了氧化应激和炎症过程,这可能间接影响高血压引起的肾脏结局。

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