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通过核因子-κB/锌指转录因子 1 信号通路抑制高尿酸血症肾病肾小管上皮细胞间质转化。

inhibits epithelial-mesenchymal transition of renal tubular cells through the NF-κB/Snail signalling pathway in hyperuricaemia nephropathy.

机构信息

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

出版信息

Pharm Biol. 2023 Dec;61(1):1274-1285. doi: 10.1080/13880209.2023.2243086.

DOI:10.1080/13880209.2023.2243086
PMID:37599625
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10443970/
Abstract

CONTEXT

Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN).

OBJECTIVE

To investigate the molecular mechanism of action of CS in HN treatment using and experiments.

MATERIALS AND METHODS

Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN.

RESULTS

HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA ( < 0.05) and blood urea nitrogen ( < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 μg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. and studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function.

DISCUSSION AND CONCLUSIONS

These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.

摘要

背景

唇形科(Labiatae)植物夏枯草(CS)是一种传统的多年生中草药,能降低血清尿酸(sUA)水平,改善肾功能,广泛用于治疗高尿酸血症肾病(HN)。

目的

通过 和 实验研究 CS 治疗 HN 的分子作用机制。

材料与方法

将 Sprague-Dawley 大鼠随机分为对照组、HN 组、CS 低剂量组(3.125g/kg)、CS 高剂量组(6.25g/kg)和阳性对照组(别嘌呤醇)。HN 组大鼠腹腔注射 750mg/kg 氧嗪酸钾(OA),CS 组大鼠在注射 OA 的同时给予 CS 灌胃(低剂量 3.125g/kg,高剂量 6.25g/kg),共 5 周。在 研究中,使用尿酸处理的 HK2 细胞验证 CS 治疗 HN 的治疗机制。

结果

HN 大鼠表现出血清尿酸水平升高和肾损伤的病理表型。CS 可显著改善这些症状和 sUA(<0.05)和血尿素氮(<0.01)水平,并显著改善 HN 大鼠的肾小管损伤。HK2 细胞中 UA(尿酸)的 IC 值为 826.32±3.55μg/mL;然而,120ng/mL 的 CS 对 HK2 细胞没有明显的细胞毒性。 和 研究表明,CS 抑制 NF-κB 磷酸化,抑制α-平滑肌肌动蛋白(α-SMA)和波形蛋白表达,同时增加 E-钙黏蛋白表达,表明 CS 抑制了肾细胞的纤维化过程,从而保护肾功能。

讨论与结论

这些发现为 CS 在 HN 治疗中的应用提供了基本的认识,以更好地指导临床干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/8f4993139067/IPHB_A_2243086_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/719b069508aa/IPHB_A_2243086_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/fce678224176/IPHB_A_2243086_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/4fe6ba7e17ef/IPHB_A_2243086_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/90d8a46b215d/IPHB_A_2243086_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/7d612c75c71a/IPHB_A_2243086_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/8f4993139067/IPHB_A_2243086_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/719b069508aa/IPHB_A_2243086_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/fce678224176/IPHB_A_2243086_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/4fe6ba7e17ef/IPHB_A_2243086_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/90d8a46b215d/IPHB_A_2243086_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/7d612c75c71a/IPHB_A_2243086_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72d5/10443970/8f4993139067/IPHB_A_2243086_F0006_C.jpg

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