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expression of α-SMA in hepatic tissue were determined， and HE and Masson staining were performed to observe the
histopathology. Using the difference multiple of expression quantity as the index，TMT technology was used to screen the
differentially expressed protein in medicine group（combining the liver tissue samples of Qiwei qinggan powder groups）and HF
model group. Uniprot-GOA database and KAAS，KEGG mapper online tools were used to analyze GO and KEGG pathway
enrichment. RESULTS：The rats in the blank group were in good health；the liver was bright red and smooth，the liver lobules
were intact，no degeneration and necrosis，inflammatory cell infiltration or fibrous tissue proliferation was found. Compared with
blank group，the rats in HF model group had poor diet，depressed spirit，disordered and lusterless fur；the liver was dark red or
yellow with rough surface，hard texture，inflammatory cell infiltration，fiber tissue destruction，bridge connection and so on；the
hepatic index，the contents of liver function indexes and the expression of α-SMA were increased significantly （P＜0.05）.
Compared with HF model group，above symptoms of rats were improved to different extent in different dose groups of Qiwei
qinggan powder；hepatic index in Qiwei qinggan powder low-dose group，the content of ALP in high-dose group，the contents of
ALT，AST and HYP and the expression of α-SMA in different dose groups were decreased significantly（P＜0.05）. A total of 42
differentially expressed proteins related to HF were screened，of which 15 were up-regulated and 27 were down-regulated in
expression，including fatty acid binding protein 4（FABP4），cholesterol 7 α-hydroxylase（CYP7A1）. The results of enrichment
analysis showed that the differentially expressed proteins were mainly enriched in extracellular space，blood particles and other cell
parts，involving the molecular functions of oxidoreductase activity and fatty acid binding，the biological processes of the regulation
of heterotypic cell adhesion，protein activation cascade，as well as retinol metabolism，arachidonic acid metabolism，PPAR and
other signal pathway. CONCLUSIONS：Qiwei qinggan powder can reduce the hepatic index，ALT，AST，ALP and HYP contents
in serum，down-regulate the expression of α-SMA，improve the degree of inflammation and fibrosis of liver tissue，and have a
certain protective effect on rats. The anti-HF mechanism of it involves multiple targets and signal pathways，such as FABP4，
CYP7A1 and PPAR.
KEYWORDS Hepatic fibrosis；Qiwei qinggan powder；Proteomics；TMT technology；Differentially expressed proteins；Rats

肝纤维化（Hepatic fibrosis，HF）是一种慢性的肝损 效；石膏性凉，有清热解毒的功效；香青兰具有清胃肝
伤疾病，主要发病原因包括病毒性肝炎、酒精肝、脂肪 热、止血的作用；瞿麦可清热解毒；五灵脂具有活血散瘀
[10]
肝、寄生虫感染、化学毒物侵害、自身免疫性疾病等 [1-3] 。 的功效；诸药合用，共奏清肝热之效 。本课题组前期
[11]
被损伤的肝脏细胞可分泌多种炎症细胞因子，后者可激 已通过动物实验证实了七味清肝散具有抗HF的作用 。
活肝星状细胞（HSC），活化的HSC可合成分泌大量的以 为进一步证明该方是通过多靶点的协同和/或竞争作用
胶原纤维为主的细胞外基质（ECM）。在此过程中， 来治疗 HF，本研究拟利用蛋白质组学的方法对其作用
ECM 的暂时增生有利于肝脏的自我修复；活化的 HSC 机制及靶点进行预测分析，旨在为后续该方抗 HF 相关
可转化为成纤维细胞进而形成多能干细胞，进而分化成 的转录组学、代谢组学的深入研究奠定基础。
肝细胞，最终有利于肝脏的重塑 [4-6] 。由此可见，上述过 1 材料
程是肝脏损伤自我修复的一种保护机制。然而，当损伤 1.1 仪器
长期累积，ECM将会大量聚集，造成肝硬化、肝癌等严重 ELx800型酶标仪（美国BioTek公司）；725型紫外分
后果，严重危害人体健康 [7-8] 。有数据显示，HF的发病率 光光度计（日本 Shimadzu 公司）；BX51 型显微镜（日本
在全世界范围内呈上升趋势；而且有研究表明，在排除 Olympus 公司）；Odyssey 型红外激光成像系统（美国
了发病原因（如饮酒）之后，HF仍可继续进展，最终导致 LI-COR 公司）；EASY-nLC 1000 型超高效液相系统、Or-
[9]
不良后果 。目前，用于治疗HF的药物大多价格昂贵且 bitrap Fusion Lumos 型三合一质谱系统（美国 Thermo
毒副作用大，临床应用受限。 Fisher Scientific 公司）；SM2010R 型切片机（德国 Leica
蒙药七味清肝散由蓝盆花、红花、人工牛黄、石膏、 公司）；3K15 型高速冷冻离心机（美国 Sigma 公司）；
香青兰、瞿麦、五灵脂等药材组成，临床可用于治疗肝热 BS2202S 型电子分析天平[塞多利斯科学仪器（北京）有
[10]
目赤、黄疸、肝区疼痛、发烧口渴、头痛等症 。方中，蓝 限公司]；HH-6型数显恒温水浴锅（常州国华电器有限公
盆花具有甘、涩、钝、燥、腻、重、凉等性味，可清热、清“协 司）。
日”、泻火，主要用于治疗肺热、肝热、咽喉热等疾病；红 1.2 药品与试剂
花味辛、性温，入心、肝、肾经，具有清肝热的作用；牛黄 蓝盆花（批号：171219，产地：内蒙古）、红花（批号：
可用于解热、解毒、定惊，具有清热凉肝、息风止痉的功 171103，产地：新疆）、瞿麦（批号：170910，产地：内蒙

中国药房 2020年第31卷第11期 China Pharmacy 2020 Vol. 31 No. 11 ·1295 ·