紫草素抑制TGF-β1/Smad信号通路改善小鼠肾纤维化的实验研究

doi:10.12092/j.issn.1009-2501.2026.01.005

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (1): 48-54.doi: 10.12092/j.issn.1009-2501.2026.01.005

• 基础研究 • 上一篇

紫草素抑制TGF-β1/Smad信号通路改善小鼠肾纤维化的实验研究

汪涛¹^,²(), 程筱雯¹^,*(), 张智瑞³, 焦浩⁴

1. 安徽医科大学第一附属医院检验科，合肥 230022，安徽
2. 皖南医学院第一附属医院（弋矶山医院）检验科，芜湖 241000，安徽
3. 皖南医学院第一附属医院（弋矶山医院）临床药学科，芜湖 241000，安徽
4. 皖南医学院第一附属医院（弋矶山医院）药事管理科，芜湖 241000，安徽

收稿日期:2024-06-17 修回日期:2024-08-05 出版日期:2026-01-26 发布日期:2026-02-13
通讯作者: 程筱雯 E-mail:m19556281637@163.com;windy135@sina.com
作者简介:汪涛，男，初级检验师，主要从事临床检测工作。E-mail：m19556281637@163.com
基金资助:
癌症转化医学安徽省重点实验室2022年底开放研究基金项目（KFZZ202204）；皖南医学院第一附属医院（弋矶山医院）人才引进项目（YR20220216）；芜湖市科技厅应用基础研究项目（2023jc29）

Shikonin restrains TGF-β1/Smad signaling pathway to improve renal fibrosis

Tao WANG¹^,²(), Xiaowen CHENG¹^,*(), Zhirui ZHANG³, Hao JIAO⁴

1. Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical College, Hefei 230022, Anhui, China
2. Department of Clinical Laboratory, First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241000, Anhui, China
3. Department of Pharmacy, First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241000, Anhui, China
4. Pharmacy Management Section, First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241000, Anhui, China

Received:2024-06-17 Revised:2024-08-05 Online:2026-01-26 Published:2026-02-13
Contact: Xiaowen CHENG E-mail:m19556281637@163.com;windy135@sina.com

摘要/Abstract

摘要：

目的: 探究紫草素（shikonin，SK）治疗小鼠肾纤维化的作用及其机制。方法: 将C57BL/6小鼠随机分为假手术组、单侧输尿管梗阻（UUO）模型组、SK低剂量组和SK高剂量组，每组8只。采用UUO法构建小鼠肾纤维化模型，造模当日开始给药。SK低剂量组和SK高剂量组小鼠分别灌胃5、20 mg·kg^?1·d^?1紫草素，假手术组和UUO组给与等体积的生理盐水，连续干预10 d。按照试剂盒检测小鼠血清中尿素氮（BUN）、肌酐（Cr）和尿酸（UA）水平，ELISA法检测血清中炎症因子IL-6、IL-1β和TNF-α水平，HE染色、Masson染色以及qRT-PCR法检测小鼠肾组织损伤程度和胶原沉积。Western blot法检测TGF-β1、p-Smad2、Smad2、p-Smad3、Smad3的蛋白表达水平。结果: 与假手术组相比，UUO组小鼠炎症因子水平、肾功能指标、纤维化相关蛋白和TGF-β1/Smad信号通路蛋白表达均显著升高（P<0.05），肾脏纤维化程度加重。与UUO组相比，紫草素组小鼠炎症因子水平、肾功能指标、纤维化相关蛋白和TGF-β1/Smad信号通路蛋白表达则明显降低，肾脏纤维化程度得到改善，且SK高剂量组改善作用更为明显，差异均具有统计学意义（P<0.05）。结论: 紫草素可能通过抑制TGF-β1/Smad信号通路减轻肾脏炎症反应和纤维化程度，改善肾功能和肾损伤状态，延缓肾纤维化进展。

关键词: 紫草素, 肾纤维化, UUO, 胶原沉积, TGF-β1/Smad信号通路

Abstract:

AIM: To explore the effect of shikonin (SK) in the treatment of renal fibrosis in mice. METHODS: C57BL/6 mice were randomly divided into sham group, UUO group, shikonin low-dose group (5 mg·kg^?1·d^?1) and high-dose group (20 mg·kg^?1·d^?1), with 8 mice in each group. Mice in the experimental group were given different concentrations of shikonin, sham group and UUO group were given equal volume of normal saline, continuous intervention for 10 days. Serum urea nitrogen (BUN), creatinine (Cr) and uric acid (UA) levels were detected by automatic differentiation analyzer, serum inflammatory factors IL-6, IL-1β and TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA), and renal tissue damage and collagen deposition were detected by HE staining, Masson staining and qRT-PCR. Use protein blotting to detect the expression levels of TGF-β1, p-Smad2, Smad2, p-Smad3, Smad3. RESULTS: Compared with the sham group, the levels of inflammatory factors, renal function indexes, fibrosis-related proteins and TGF-β1/Smad signaling pathway proteins in UUO group were significantly increased (P<0.05), and the degree of renal fibrosis was aggravated. Compared with UUO group, the levels of inflammatory factors, renal function indexes, fibrosis-related proteins and TGF-β1/Smad signaling pathway proteins in the SK group were significantly decreased, and the degree of renal fibrosis was improved, and the improvement was more obvious in the SK high-dose group, with statistical significance (P<0.05). CONCLUSION: Shikonin may alleviate renal inflammation and fibrosis by inhibiting the TGF-β1/Smad signaling pathway, improve renal function and kidney injury status, and play a role in alleviating the progression of renal fibrosis.

Key words: shikonin, renal fibrosis, UUO, collagen deposition, TGF-β1/Smad signaling pathway

中图分类号:

R965.2

汪涛, 程筱雯, 张智瑞, 焦浩. 紫草素抑制TGF-β1/Smad信号通路改善小鼠肾纤维化的实验研究[J]. 中国临床药理学与治疗学, 2026, 31(1): 48-54.

Tao WANG, Xiaowen CHENG, Zhirui ZHANG, Hao JIAO. Shikonin restrains TGF-β1/Smad signaling pathway to improve renal fibrosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(1): 48-54.

图/表 6

表 1

Table 1 Comparison of serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) levels in each group of mice (n=5, $\overline x $±s)

Group	IL-6 (pg/mL)	IL-1β (ng/L)	TNF-α (ng/L)
Sham	19.89±4.54	23.88±5.13	343.85±33.36
UUO	112.25±11.76^b	69.66±4.61^b	903.84±32.09^b
SK-L	85.01±5.86^e	55.76±3.22^e	712.27±62.80^e
SK-H	59.37±9.51^e	43.71±4.18^e	548.81±76.54^e

表 2

Table 2 Comparion of serum blood urea nitrogen (BUN), creatinine (Cr) and Uric Acid (UA) levels in each group of mice (n=5, $\overline x $±s)

Group	BUN (mmol/L)	Cr (μmol/L)	UA (μmol/L)
Sham	3.02±0.27	2.88±0.55	91.00±10.12
UUO	10.70±1.71^b	153.4±11.55^b	215.20±11.63^b
SK-L	7.94±0.62^e	112.20±8.81^e	162.00±11.02^e
SK-H	5.22±0.98^e	82.40±9.53^e	128.60±11.44^e

图 1

Fig.1 Observation of renal pathology morphology by hematoxylin and eosin (HE) staining (×200) A: Sham group; B: UUO group; C: 5 mg·kg−1·d−1 shikonin group; D: 20 mg·kg−1·d−1 shikonin group.

图 2

Fig.2 Observation of renal fibrosis by Masson staining (×200) A: sham group; B: UUO group; C: 5 mg·kg−1·d−1 shikonin group; D: 20 mg·kg−1·d−1 shikonin group.

图 3

Fig.3 Collagen I and α-SMA expression in kidney tissues of each group (×200) A: sham group; B: UUO group; C: 5 mg·kg−1·d−1 shikonin group; D: 20 mg·kg−1·d−1 shikonin group.

图 4 bP<0.05,cP<0.01, compared with sham group; eP<0.05,fP<0.01, compared with UUO group.

Fig.4 Western blot analysis of the effects of SK on the expression of TGF-β1/Smad signaling pathway in mouse kidney ($\bar x $±s, n=3) bP<0.05,cP<0.01, compared with sham group; eP<0.05,fP<0.01, compared with UUO group.

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紫草素抑制TGF-β1/Smad信号通路改善小鼠肾纤维化的实验研究

Shikonin restrains TGF-β1/Smad signaling pathway to improve renal fibrosis

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