活血清解灵通过调控Sirt1-自噬信号通路减轻胆管结扎诱导的大鼠肝纤维化

doi:10.12122/j.issn.1673-4254.2026.03.05

摘要/Abstract

摘要：

目的探讨活血清解灵（HXQJL）通过调控沉默信息调节因子1（Sirt1）信号通路介导的自噬改善胆管结扎（BDL）诱导的肝纤维化。方法采用BDL处理SD大鼠，并随机分为：假手术组（Sham）、模型组（BDL）、活血清解灵低、高剂量组（HXQJL-L、HXQJL-H），Sirt1抑制剂Ex527组（EX527），活血清解灵联合Ex527组（HXQJL+EX527）。HE和天狼星红染色观察肝组织病变和胶原沉积变化；生化检测血清ALT、AST、ALP和GGT水平。RT-PCR 和Western blotting法分别检测α-SMA、FN、COL I、Atg 5、Beclin1、p62、LC3B和Sirt1 的表达。免疫荧光检测α-SMA、LC3B和Sirt1的表达。结果与Sham组比较，BDL组肝细胞损伤、炎细胞浸润及胶原沉积面积增多（P<0.05），血清中ALT、AST、ALP、GGT水平增加（P<0.05）。同时肝组织中α-SMA、FN、COL I、Atg 5和Beclin1表达增加， LC3B-II/I比值增加（P<0.05），而p62和Sirt1表达降低（P<0.05）。与BDL组相比，活血清解灵各剂量组肝细胞损伤、炎细胞浸润及胶原沉积面积减少（P<0.05），ALT、AST、TBA、ALP水平降低（P<0.05），肝组织中α-SMA、FN、COL I、Atg 5和Beclin1表达降低（P<0.05），LC3B-II/I比值降低，而p62和Sirt1表达增加（P<0.05）；而Ex527组肝细胞损伤、炎细胞浸润及胶原沉积面积增多（P<0.05），ALT、AST、TBA、ALP水平升高（P<0.05），肝组织中α-SMA、FN、COL I、Atg 5和Beclin1表达升高，LC3B-II/I比值升高（P<0.05），而p62和Sirt1表达降低（P<0.05）。与HXQJL-H组相比， Ex527可以阻断活血清解灵对大鼠肝组织损伤、肝功能、肝纤维化和自噬的作用。结论活血清解灵通过调控Sirt1-自噬信号通路对胆管结扎诱导肝纤维化具有保护作用。

关键词: 活血清解灵, 肝纤维化, 自噬, Sirt1, EX527

Abstract:

Objective To investigate the protective effect of Huoxue Qingjie Ling (HXQJL) agaisnt bile duct ligation (BDL)-induced liver fibrosis in rats and the underlying mechanism. Methods SD rats were randomized into sham-operated group, BDL model group, low- and high-dose HXQJL treatment groups, Ex527 (a Sirt1 inhibitor) group (EX527), and HXQJL+Ex527 group. Liver histopathological changes and collagen deposition were observed using HE and Sirius Red staining, and serum levels of ALT, AST, ALP, and GGT of the rats were measured using biochemical assays. The expression levels of α‑SMA, FN, COL I, Atg5, Beclin1, p62, LC3B, and Sirt1 were determined by RT-PCR and Western blotting. Immunofluorescence staining was used to detect the expression of α-SMA, LC3B, and Sirt1. Results Compared with the sham-operated rats, the rats in BDL model group exhibited increased hepatocyte injury, inflammatory cell infiltration, and collagen deposition area with elevated serum levels of ALT, AST, ALP, and GGT, enhanced haptic expressions of α‑SMA, FN, COL I, Atg5, and Beclin1, an increased LC3B-II/I ratio, and lowered hepatic expressions of p62 and Sirt1. All these changes were significantly alleviated in the two HXQJL treatment groups but aggravated in EX527 treatment group. Compared with those in high-dose HXQJL group, the protective effects of HXQJL on liver tissue injury, liver function, liver fibrosis, and autophagy were obviously mitigated by treatment with Ex527. Conclusion HXQJL has protective effect against BDL-induced liver fibrosis in rats by modulating the Sirt1-autophagy signaling pathway.

Key words: Huoxue Qingjie Ling, hepatic fibrosis, autophagy, Sirt1, EX527

李彩霞, 崔立华, 曹婕, 樊宇星, 周雪颖, 张淑坤, 左艳洁. 活血清解灵通过调控Sirt1-自噬信号通路减轻胆管结扎诱导的大鼠肝纤维化[J]. 南方医科大学学报, 2026, 46(3): 513-522.

Caixia LI, Lihua CUI, Jie CAO, Yuxing FAN, Xueying ZHOU, Shukun ZHANG, Yanjie ZUO. Huoxue Qingjie Ling alleviates bile duct ligation-induced hepatic fibrosis in rats by regulating the Sirt1-autophagy signaling pathway[J]. Journal of Southern Medical University, 2026, 46(3): 513-522.

图/表 17

表1 引物序列

Tab.1 Primer sequences for qRT-PCR

Gene	Primer sequences (5'-3') (Forward)	Primer sequences (5'-3') (Reverse)
FN	GATTCTTCTGGCGTCTGCAC	GATTCTTCTGGCGTCTGCAC
COL I	GGATAGGGACTTGTGTGA	GCTGGAAGAGTGAAGAGG
α-SMA	AGGGAGTGATGGTTGGAATG	GATGATGCCGTGTTCTATCG
Beclin-1	AGGGAGTGATGGTTGGAATG	GATGATGCCGTGTTCTATCG
Atg5	AGGGAGTGATGGTTGGAATG	GATGATGCCGTGTTCTATCG
LC3B	AGGGAGTGATGGTTGGAATG	GATGATGCCGTGTTCTATCG
P62	ACGACTGGACGCATTTGTCT	TGGTGGGAGATGTGGGATCA
Sirt 1	ACCGAGACAACCTCCTGTTG	ATGGACCTATCCGTGGCCTT
GAPDH	AGATGGGTGAAGGTCGGTGTG	CTGGAAGATGGTGATGGGTT

表2 活血清解灵对BDL诱导肝纤维化大鼠体质量、肝脏质量和肝脏指数的影响

Tab.2 Effect of Huoxue Qingjie Ling (HXQJL) on body weight, liver mass and liver index in rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	Body mass (g)	Liver mass (g)	Liver index (%)
Sham		296.0±6.6	11.4±1.0	3.8±0.3
BDL		198.1±11.8¹⁾	17.9±1.8¹⁾	9.0±0.8¹⁾
HXQJL-L	7.74	235.6±11.2²⁾	14.9±0.8²⁾	6.3±0.4²⁾
HXQJL-H	15.48	258.2±10.9²⁾³⁾	12.4±1.3²⁾³⁾	4.8±0.6²⁾
EX527	0.005	163.6±8.8²⁾	21.4±1.0²⁾	13.1±1.0²⁾
EX527+HXQJL	0.005+15.48	204.0±13.0⁴⁾	17.5±2.1⁴⁾	8.6±0.9⁴⁾

表3 活血清解灵对BDL诱导肝纤维化大鼠血清ALT、AST、ALP和GGT水平的影响

Tab.3 Effect of HXQJL on serum levels of ALT, AST, ALP and GGT in rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	ALT (U/L)	AST (U/L)	ALP (U/L)	GGT (U/L)
Sham		52.0±15.8	136.8±13.3	155±26.9	1.8±0.7
BDL		128.2±13.1¹⁾	383.3±71¹⁾	389.2±53.5¹⁾	47.7±19.6¹⁾
HXQJL-L	7.74	59.3±9.6²⁾	182.8±20.5²⁾	214.7±31.4²⁾	15.8±4.2²⁾
HXQJL-H	15.48	53.6±7.4²⁾	141.9±28.1²⁾	179.4±57.6²⁾	10.1±4.9²⁾
EX527	0.005	169.7±16.4²⁾	490±107.8²⁾	577.5±70.9²⁾	78.2±7.7²⁾
EX527+HXQJL	0.005+15.48	105.7±31.6⁴⁾ 289.7±101.3⁴⁾		361.2±54.2⁴⁾	41.3±14.4⁴⁾

图1 活血清解灵对 BDL诱导的肝纤维化大鼠肝组织 HE 染色和天狼星红染色的影响

Fig.1 HE staining (Original magnification: ×200) and Sirius red staining (×100) of the liver tissue of rats in different groups.

表4 活血清解灵对BDL诱导肝纤维化大鼠肝组织病理学损伤的影响

Tab.4 Effect of HXQJL on liver histopathological damage in rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	Pathology score	Sirius red positive area (%)
Sham		1.2±0.1	3.2±0.6
BDL		3.9±0.3¹⁾	47.5±7.8¹⁾
HXQJL-L	7.74	1.9±0.3²⁾	28.9±5.5²⁾
HXQJL-H	15.48	1.6±0.1²⁾	16.0±2.2^{2) 3)}
EX527	0.005	5.3±0.5²⁾	64.9±5.4²⁾
EX527+HXQJL	0.005+15.48	3.1±0.6⁴⁾	47.3±3.2²⁾

表 5 活血清解灵对BDL诱导肝纤维化大鼠肝组织中FN、COL I和α-SMA mRNA表达的影响

Tab.5 Effect of HXQJL on mRNA level of FN, COL I and α-SMAin the liver tissues of rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	FN	COL I	α-SMA
Sham		1.00±0.19	1.00±0.08	1.03±0.15
BDL		2.84±0.62¹⁾	11.87±3.15¹⁾	4.62±1.12¹⁾
HXQJL-L	7.74	1.62±0.26²⁾	6.07±1.19²⁾	2.67±0.62²⁾
HXQJL-H	15.48	1.36±0.44²⁾	3.46±0.69²⁾	1.79±0.47²⁾
EX527	0.005	5.36±1.06²⁾	18.96±3.36²⁾	8.56±1.39²⁾
EX527+HXQJL	0.005+15.48	3.08±1.40⁴⁾	13.79±4.92⁴⁾	3.91±1.5⁴⁾

图2 HXQJL对 BDL诱导的肝纤维化大鼠肝组织中FN 、COL I和α-SMA蛋白表达的影响

Fig.2 Effect of HXQJL on expression of FN, COL I and α‑SMA protein in liver tissues in rats with BDL-induced liver fibrosis. A: Sham group; B: BDL group; C: HXQJL-L group; D: HXQJL-H group; E: EX527 group; F: EX527+HXQJL group.

表6 活血清解灵对BDL诱导肝纤维化大鼠肝组织中FN 、COL I和α-SMA蛋白表达的影响

Tab.6 Effect of HXQJL on protein expression levels of FN, COL I and α-SMAin the liver tissues of rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	FN	COL I	α-SMA
Sham		0.11±0.02	0.14±0.03	0.36±0.06
BDL		0.36±0.02¹⁾	0.38±0.01¹⁾	0.75±0.07¹⁾
HXQJL-L	7.74	0.14±0.01	0.20±0.03²⁾	0.40±0.01²⁾
HXQJL-H	15.48	0.12±0.01²⁾	0.17±0.03²⁾	0.33±0.04²⁾
EX527	0.005	2.33±0.17²⁾	1.12±0.11²⁾	1.22±0.10²⁾
EX527+HXQJL	0.005+15.48	1.44±0.13⁴⁾	0.70±0.06⁴⁾	1.00±0.02⁴⁾

图3 活血清解灵对 BDL诱导的肝纤维化大鼠肝组织中α-SMA蛋白表达的影响

Fig.3 Effect of HXQJL onα-SMA expression in the liver tissues of rats with BDL-induced liver fibrosis(×200). A: Sham group; B: BDL group; C: HXQJL-L group; D: HXQJL-H group; E: EX527 group; F: EX527+HXQJL group.

表7 活血清解灵对BDL诱导肝纤维化大鼠肝组织中Beclin-1、Atg5、LC3B 和 p62 mRNA 表达的影响

Tab.7 Effect of HXQJL on mRNA levels of Beclin-1, Atg5, LC3B and p62in the liver tissues of rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Groups	Dose (g/kg)	Beclin-1	Atg5	LC3B	p62
Sham		1.01±0.08	1.00±0.20	1.00±0.17	1.00±0.14
BDL		2.13±0.49¹⁾	1.61±0.12¹⁾	1.48±0.14¹⁾	0.63±0.10¹⁾
HXQJL-L	7.74	1.11±0.08²⁾	1.09±0.18²⁾	0.92±0.16²⁾	0.83±0.18²⁾
HXQJL-H	15.48	1.03±0.18²⁾	0.85±0.20²⁾	0.83±0.25²⁾	0.98±0.14²⁾
EX527	0.005	2.99±0.25²⁾	2.01±1.38²⁾	1.92±0.17²⁾	0.24±0.08²⁾
EX527+HXQJL	0.005+15.48	1.91±0.43⁴⁾	1.5±0.30⁴⁾	1.47±0.27⁴⁾	0.68±0.16⁴⁾

图4 活血清解灵对 BDL诱导的肝纤维化大鼠肝组织中Beclin-1、Atg5、LC3B 和p62蛋白表达的影响

Fig. 4 Effect of HXQJL on expressions of Beclin-1, Atg5, LC3B and p62 in the liver tissues of rats with BDL-induced liver fibrosis. A: Sham group; B: BDL group; C: HXQJL-L group; D: HXQJL-H group; E: EX527 group; F: EX527+HXQJL group.

表8 活血清解灵对BDL诱导肝纤维化大鼠肝组织中Beclin-1、Atg5、LC3B 和 p62蛋白表达的影响

Tab.8 Effect of HXQJL on protein level of Beclin-1, Atg5, LC3B and p62in the liver tissues of rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	Beclin-1	Atg5	p62	LC3B-II/LC3B-I
Sham		0.48±0.01	0.60±0.04	1.25±0.11	1.81±0.01
BDL		0.77±0.02¹⁾	0.99±0.07¹⁾	0.43±0.03¹⁾	2.35±0.12¹⁾
HXQJL-L	7.74	0.52±0.03²⁾	0.73±0.03²⁾	0.57±0.03	2.14±0.02²⁾
HXQJL-H	15.48	0.49±0.02²⁾	0.67±0.04²⁾	0.83±0.07²⁾	1.83±0.02²⁾
EX527	0.005	1.15±0.11²⁾	1.27±0.08²⁾	0.25±0.05²⁾	2.66±0.03²⁾
EX527+HXQJL	0.005+15.48	0.78±0.10⁴⁾	0.86±0.03⁴⁾	0.47±0.03⁴⁾	2.56±0.09⁴⁾

图 5 活血清解灵对 BDL诱导的肝纤维化大鼠肝组织中LC3B蛋白表达的影响

Fig.5 Effect of HXQJL on expressions of LC3B in the liver tissues of rats with BDL-induced liver fibrosis (×200). A: Sham group; B: BDL group; C: HXQJL-L group; D: HXQJL-H group; E: EX527 group; F: EX527+HXQJL group.

表 9 活血清解灵对BDL诱导肝纤维化大鼠肝组织中Sirt 1mRNA 表达的影响

Tab.9 Effect of HXQJL on mRNA level ofSirt1in the liver tissues of the rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	Sirt 1
Sham		1.00±0.14
BDL		0.60±0.04¹⁾
HXQJL-L	7.74	0.99±0.11²⁾
HXQJL-H	15.48	0.99±0.08²⁾
EX527	0.005	0.28±0.08²⁾
EX527+HXQJL	0.005+15.48	0.51±0.15⁴⁾

图 6 活血清解灵对 BDL诱导的肝纤维化大鼠肝组织中Sirt 1蛋白表达的影响

Fig.6 Effect of HXQJL on expression of Sirt 1 in liver tissues in rats with BDL-induced liver fibrosis. A: Sham group; B: BDL group; C: HXQJL-L group; D: HXQJL-H group; E: EX527 group; F: EX527+HXQJL group.

表10 活血清解灵对BDL诱导肝纤维化大鼠肝组织中Sirt 1蛋白表达的影响

Tab.10 Effect of HXQJL on protein level of Sirt1in the liver tissues of the rats with BDL-induced liver fibrosis (Mean±SD, n=8)

Group	Dose (g/kg)	Sirt 1
Sham		1.14±0.10
BDL		0.43±0.04¹⁾
HXQJL-L	7.74	1.09±0.04²⁾
HXQJL-H	15.48	1.13±0.10²⁾
EX527	0.005	0.21±0.01²⁾
EX527+HXQJL	0.005+15.48	0.39±0.03⁴⁾

图 7 活血清解灵对 BDL诱导的肝纤维化大鼠肝组织中Sirt 1蛋白表达的影响

Fig.7 Effect of HXQJL on Sirt 1 expression in the liver tissues of the rats with BDL-induced liver fibrosis(×200). A: Sham group; B: BDL group; C: HXQJL-L group; D: HXQJL-H group; E: EX527 group; F: EX527+HXQJL group.

参考文献 31

[1]	Horn P, Tacke F. Metabolic reprogramming in liver fibrosis[J]. Cell Metab, 2024, 36(7): 1439-55. doi：10.1016/j.cmet.2024.05.003
[2]	Filali-Mouncef Y, Hunter C, Roccio F, et al. The ménage à trois of autophagy, lipid droplets and liver disease[J]. Autophagy, 2022, 18(1): 50-72. doi：10.1080/15548627.2021.1895658
[3]	Hernández-Gea V, Ghiassi-Nejad Z, Rozenfeld R, et al. Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues[J]. Gastroenterology, 2012, 142(4): 938-46. doi：10.1053/j.gastro.2011.12.044
[4]	Ma LQ, Fu RG, Duan ZY, et al. Sirt1 is essential for resveratrol enhancement of hypoxia-induced autophagy in the type 2 diabetic nephropathy rat[J]. Pathol Res Pract, 2016, 212(4): 310-8. doi：10.1016/j.prp.2016.02.001
[5]	Gu LN, Tao XF, Xu YW, et al. Dioscin alleviates BDL- and DMN-induced hepatic fibrosis via Sirt1/Nrf2-mediated inhibition of p38 MAPK pathway[J]. Toxicol Appl Pharmacol, 2016, 292: 19-29. doi：10.1016/j.taap.2015.12.024
[6]	李锡晶, 沈洪昇, 王璐瑶, 等. 基于TGR5/NLRP3信号通路探讨活血清解灵对非酒精性脂肪性肝炎大鼠炎症反应的影响[J]. 中国现代应用药学, 2024, 41(10): 1324-31. doi：10.13748/j.cnki.issn1007-7693.20224076
[7]	无徐列明, 刘平, 沈锡中, 等. 肝纤维化中西医结合诊疗指南(2019年版)[J]. 中国中西医结合杂志, 2019, 39(11): 1286-95.
[8]	李婉华, 张桂贤, 沈洪昇, 等. 基于TGR5-NLRP3-Caspase1通路探讨活血清解灵对大鼠胆汁淤积性肝病的治疗作用[C]//第15届中国中西医结合学会基础理论专业委员会学术年会暨第二届广东省中西医结合学会转化医学专业委员会年会论文集. 广州, 2019: 47-8.
[9]	Cai YJ, Zheng Q, Sun R, et al. Recent progress in the study of Artemisiae Scopariae Herba (Yin Chen), a promising medicinal herb for liver diseases[J]. Biomed Pharmacother, 2020, 130: 110513. doi：10.1016/j.biopha.2020.110513
[10]	Gijbels E, Pieters A, De Muynck K, et al. Rodent models of cholestatic liver disease: a practical guide for translational research[J]. Liver Int, 2021, 41(4): 656-82. doi：10.1111/liv.14800
[11]	Ibrahim SH, Kamath BM, Loomes KM, et al. Cholestatic liver diseases of genetic etiology: Advances and controversies[J]. Hepatology, 2022, 75(6): 1627-46. doi：10.1002/hep.32437
[12]	王琳琳, 朱正望, 赵静涵, 等. 茵陈蒿汤对胆汁淤积性肝损伤的干预作用及调控机制[J/OL]. 中国实验方剂学杂志, 2025: 1-18. (2025-04-22). .
[13]	向杰, 邓敏贞, 李泽森, 等. 茵陈蒿汤方剂挥发油对肝纤维化小鼠的治疗作用及其机制[J]. 暨南大学学报: 自然科学与医学版, 2023, 44(6): 563-75. doi：10.11778/j.jdxb.20230125
[14]	朱晓东, 邸学士, 杨佳潞, 等. 基于网络药理学探讨茵陈蒿汤治疗肝纤维化的作用机制[J]. 中医药学报, 2021, 49(6): 29-36. doi：10.19664/j.cnki.1002-2392.210134
[15]	王晶, 欧阳冰琛. 茵陈蒿汤防治肝脏疾病的药理作用及药动学研究进展[J]. 药物评价研究, 2021, 44(3): 628-37. doi：10.7501/j.issn.1674-6376.2021.03.026
[16]	Cui XY, Zhang RH, Li YF, et al. Bie Jia Jian pill ameliorates BDL-induced cholestatic hepatic fibrosis in rats by regulating intestinal microbial composition and TMAO-mediated PI3K/AKT signaling pathway[J]. J Ethnopharmacol, 2025, 337(Pt 2): 118910. doi：10.1016/j.jep.2024.118910
[17]	Xiao Z, Gao SQ, Li SS, et al. Taohong Siwu Decoction modulates glutathione metabolism to suppress hepatocyte ferroptosis and demonstrates anti-fibrotic effects in the liver[J]. J Ethnopharmacol, 2025, 350: 120025. doi：10.1016/j.jep.2025.120025
[18]	Qu JR, Xue XY, Wang ZX, et al. Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition[J]. Chin J Nat Med, 2024, 22(1): 31-46. doi：10.1016/s1875-5364(24)60560-1
[19]	Liu HM, Dong F, Li GQ, et al. Liuweiwuling tablets attenuate BDL-induced hepatic fibrosis via modulation of TGF-β/Smad and NF-κB signaling pathways[J]. J Ethnopharmacol, 2018, 210: 232-41. doi：10.1016/j.jep.2017.08.029
[20]	Hou LS, Zhai XP, Zhang YW, et al. Targeted inhibition of autophagy in hepatic stellate cells by hydroxychloroquine: an effective therapeutic approach for the treatment of liver fibrosis[J]. Liver Int, 2024, 44(8): 1937-51. doi：10.1111/liv.15915
[21]	Liu Y, Yao L, Liu YY, et al. Micheliolide alleviates hepatic fibrosis by inhibiting autophagy in hepatic stellate cells via the TrxR1/2-mediated ROS/MEK/ERK pathway[J]. Pharmaceuticals (Basel), 2025, 18(3): 287. doi：10.3390/ph18030287
[22]	Wu LW, Zhang QH, Mo WH, et al. Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-β1/Smads and PI3K/Akt pathways[J]. Sci Rep, 2017, 7: 9289. doi：10.1038/s41598-017-09673-5
[23]	Ji J, Yu Q, Dai WQ, et al. Apigenin alleviates liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-β 1/Smad3 and p38/PPAR α pathways[J]. PPAR Res, 2021, 2021: 6651839. doi：10.1155/2021/6651839
[24]	Qin TT, Hasnat M, Wang ZW, et al. Geniposide alleviated bile acid-associated NLRP3 inflammasome activation by regulating SIRT1/FXR signaling in bile duct ligation-induced liver fibrosis[J]. Phytomedicine, 2023, 118: 154971. doi：10.1016/j.phymed.2023.154971
[25]	Xia Y, Luo QH, Gao Q, et al. SIRT1 activation ameliorates Rhesus monkey liver fibrosis by inhibiting the TGF‑β/smad signaling pathway[J]. Chem Biol Interact, 2024, 394: 110979. doi：10.1016/j.cbi.2024.110979
[26]	Zheng W, Guan F, Xu G, et al. FAT10 silencing prevents liver fibrosis through regulating SIRT1 expression in hepatic stellate cells[J]. Int J Med Sci, 2023, 20(4): 557-65. doi：10.7150/ijms.77367
[27]	Lu HJ, Zhang RH, Zhang SK, et al. HSC-derived exosomal miR-199a-5p promotes HSC activation and hepatocyte EMT via targeting SIRT1 in hepatic fibrosis[J]. Int Immunopharmacol, 2023, 124(Pt B): 111002. doi：10.1016/j.intimp.2023.111002
[28]	Yang L, Ao QF, Zhong QM, et al. SIRT1/IGFBPrP1/TGF β1 axis involved in cucurbitacin B ameliorating concanavalin A-induced mice liver fibrosis[J]. Basic Clin Pharmacol Toxicol, 2020, 127(5): 371-9. doi：10.1111/bcpt.13446
[29]	Zhu J, Wang RW, Xu T, et al. Salvianolic acid a attenuates endoplasmic reticulum stress and protects against cholestasis-induced liver fibrosis via the SIRT1/HSF1 pathway[J]. Front Pharmacol, 2018, 9: 1277. doi：10.3389/fphar.2018.01277
[30]	Patra S, Praharaj PP, Singh A, et al. Targeting SIRT1-regulated autophagic cell death as a novel therapeutic avenue for cancer prevention[J]. Drug Discov Today, 2023, 28(9): 103692. doi：10.1016/j.drudis.2023.103692
[31]	Mei ZG, Huang YG, Feng ZT, et al. Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway[J]. Aging (Albany NY), 2020, 12(13): 13187-205. doi：10.18632/aging.103420