绿原酸通过 BMP-7 和 HGF 的抗纤维化作用减轻肾脏纤维化。

Chlorogenic acid attenuates kidney fibrosis via antifibrotic action of BMP-7 and HGF.

机构信息

Universitas Gadjah Mada, Public Health, and Nursing, Faculty of Medicine, Department of Anatomy, Jl. Farmako Sekip Utara, Yogyakarta, Indonesia.

Universitas Tadulako, Faculty of Medicine, Department of Anatomy, Tondo, Mantikulore, Palu City, Central Sulawesi, Indonesia.

出版信息

Med J Malaysia. 2020 May;75(Suppl 1):5-9.

PMID:32471962

Abstract

BACKGROUND

Kidney fibrosis, characterised by tubulointerstitial fibrosis, is a histological landmark of chronic kidney disease. The body attempts to compensate for progressive detrimental process of kidney fibrosis by producing antifibrotic substances, such as bone morphogenetic protein-7 (BMP-7) and hepatocyte growth factor (HGF). Chlorogenic acid is known to have renoprotective and antifibrotic properties. This study aims to evaluate the effect of chlorogenic acid on unilateral ureteral obstruction (UUO)-induced kidney fibrosis mice model.

METHODS

This study was a quasi-experimental with posttestonly control group design. Twenty-five adult male Swiss Webster mice were randomly divided into five groups: shamoperated group (SO), UUO-control day-7 (U7), UUO-control day-14 (U14), UUO-chlorogenic acid day-7 (UC7), and UUOchlorogenic acid day 14 (UC14). Myofibroblasts were identified by immunohistochemical staining of alphasmooth muscle actin (α-SMA) while collagen fibers were identified by Sirius Red staining. Both data were presented as area fraction. BMP-7 and HGF mRNA expressions were assessed by reverse transcription PCR (RT-PCR). Data were quantified using ImageJ software.

RESULTS

UUO-control groups (U7 and U14) showed higher α- SMA-immunopositive (6.52±1.33, 18.24±1.39 vs. 0.22±0.01; p<0.05) and Sirius Red-positive area fractions (6.61±0.8, 12.98±2.31 vs. 0.62±0.10; p<0.05), lower BMP-7 (1.02±0.47, 1.18±0.65 vs. 2.09±0.87; p<0.05) and HGF mRNA expressions (1.06±0.31, 0.89±0.14 vs. 1.88±0.81; p<0.05) compared to SO group. UUO-chlorogenic acid groups (UC7 and UC14) showed lower α-SMA-immunopositive (1.24±0.37, 4.58±0.61; p<0.05) and Sirius Red-positive area fractions (4.76±1.03, 3.72±0.54; p<0.05), higher BMP-7 (1.84±0.49, 2.19±0.43; p<0.05) and HGF (1.58±0.38; p>0.05, 1.84±0.42; p<0.05) mRNA expressions compared to UUO-control groups. UUOchlorogenic acid groups showed BMP-7 and HGF mRNA expressions that were not significantly different from the SO group.

CONCLUSION

Chlorogenic acid administration prevents kidney fibrosis in UUO mice model through modulating antifibrotic pathway.

摘要

背景

肾小管间质纤维化是慢性肾脏病的组织学标志，其特征是肾纤维化。为了代偿肾纤维化的进行性损害，机体产生了一些抗纤维化物质，如骨形态发生蛋白-7（BMP-7）和肝细胞生长因子（HGF）。绿原酸具有肾保护和抗纤维化的特性。本研究旨在评估绿原酸对单侧输尿管梗阻（UUO）诱导的肾纤维化小鼠模型的影响。

方法

这是一项准实验性研究，采用后测仅有对照组的设计。25 只成年雄性瑞士韦伯斯特小鼠被随机分为五组：假手术组（SO）、UUO 对照组第 7 天（U7）、UUO 对照组第 14 天（U14）、UUO 绿原酸组第 7 天（UC7）和 UUO 绿原酸组第 14 天（UC14）。α-平滑肌肌动蛋白（α-SMA）的免疫组织化学染色鉴定肌成纤维细胞，而天狼星红染色鉴定胶原纤维。这两个数据都以面积分数表示。采用逆转录 PCR（RT-PCR）评估 BMP-7 和 HGF mRNA 的表达。使用 ImageJ 软件对数据进行量化。

结果

UUO 对照组（U7 和 U14）的α-SMA 免疫阳性（6.52±1.33、18.24±1.39 与 0.22±0.01；p<0.05）和天狼星红阳性面积分数（6.61±0.8、12.98±2.31 与 0.62±0.10；p<0.05）更高，BMP-7（1.02±0.47、1.18±0.65 与 2.09±0.87；p<0.05）和 HGF mRNA 表达（1.06±0.31、0.89±0.14 与 1.88±0.81；p<0.05）更低，与 SO 组相比。UUO 绿原酸组（UC7 和 UC14）的α-SMA 免疫阳性（1.24±0.37、4.58±0.61；p<0.05）和天狼星红阳性面积分数（4.76±1.03、3.72±0.54；p<0.05）更低，BMP-7（1.84±0.49、2.19±0.43；p<0.05）和 HGF（1.58±0.38；p>0.05，1.84±0.42；p<0.05）mRNA 表达更高，与 UUO 对照组相比。UUO 绿原酸组的 BMP-7 和 HGF mRNA 表达与 SO 组无显著差异。