Page 33 - 《中国药房》2021年21期

·药学研究·

扶脾柔肝颗粒对肝纤维化模型大鼠的改善作用机制研究 Δ

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安祯祥 ，何远利，唐东昕，黄 丹，王 敏，王 芳（贵州中医药大学第一附属医院消化内科，贵阳 550001）

中图分类号 R285.5 文献标志码 A 文章编号 1001-0408（2021）21-2587-06
DOI 10.6039/j.issn.1001-0408.2021.21.05
摘 要 目的：研究扶脾柔肝颗粒（FRG）对肝纤维化模型大鼠的改善作用机制。方法：将大鼠随机分为空白组、模型组、秋水仙碱
片组（化学药阳性对照，0.2 mg/kg）、扶正化瘀胶囊组（中药阳性对照，0.415 g/kg）和FRG低、中、高剂量组（20、40、80 g/kg），除空白
组和模型组各11只大鼠外（各取1只用于判断是否造模成功），其余每组10只。除空白组外，其余各组大鼠腹腔注射50％ CCl4橄
榄油溶液并灌胃30％乙醇以复制肝纤维化模型。造模成功后，各给药组大鼠灌胃相应药物，空白组和模型组大鼠灌胃等体积生
理盐水，每天1次，连续4周。末次灌胃后，观察大鼠肝组织病理形态学变化；检测大鼠血清中透明质酸（HA）、层粘连蛋白（LN）、
Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原蛋白（Col Ⅳ）水平；检测大鼠肝组织中Beclin-1、LC3-Ⅱ蛋白表达水平；检测大鼠肝组织中蛋白激酶
B（Akt）、腺苷酸活化蛋白激酶（AMPK）、哺乳动物雷帕霉素靶蛋白（mTOR）、p70核糖体蛋白S6激酶（p70S6K）的mRNA和蛋白表
达水平。结果：与空白组比较，模型组大鼠肝小叶结构紊乱，纤维组织增生明显，部分有假小叶形成；血清中HA、LN、PCⅢ、Col Ⅳ
水平和肝组织中 Beclin-1、LC3-Ⅱ蛋白表达水平以及 Akt、AMPK、mTOR、p70S6K 的 mRNA 和蛋白表达水平均显著升高（P＜
0.01）。与模型组比较，FRG各剂量组大鼠肝组织损伤明显减轻，血清和肝组织中上述指标（FRG低剂量组LN 、PCⅢ除外）水平均
显著降低（P＜0.05或P＜0.01）。结论：FRG可改善大鼠肝纤维化，其作用机制可能与下调肝组织中自噬相关蛋白和Akt/AMPK/
mTOR/p70S6K信号通路相关蛋白的表达有关。
关键词 扶脾柔肝颗粒；肝纤维化；自噬；Akt/AMPK/mTOR/p70S6K信号通路；大鼠

Mechanism of Improvement Effects of Fupi Rougan Granules on Hepatic Fibrosis Model Rats
AN Zhenxiang，HE Yuanli，TANG Dongxin，HUANG Dan，WANG Min，WANG Fang（Dept. of Gastroenterology，
the First Affiliated Hospital of Guizhou University of TCM，Guiyang 550001，China）

ABSTRACT OBJECTIVE：To study the mechanism of improvement effects of Fupi rougan granule（FRG）on hepatic fibrosis
model rats. METHODS：The rats were randomly divided into blank group，model group，Colchicine tablet group （chemical
positive control，0.2 mg/kg），Fuzheng huayu capsule group（TCM positive control，0.415 g/kg），FRG low-dose，medium-dose
and high-dose groups（20，40，80 g/kg），with 10 rats in each group，except for 11 rats in blank group and model group（one rat
was used to judge whether the modeling was successful）. Except for blank group，other groups were given intraperitoneal injection
of 50％ CCl4 olive oil solution and intragastric administration of 30％ ethanol to induce hepatic fibrosis model. After modeling，
administration groups were given relevant medicine intragastrically；blank group and model group were given constant volume of
normal saline intragastrically，once a day，for consecutive 4 weeks. After last administration，morphology changes of liver tissue in
rats were observed. The serum levels of HA，LN，PCⅢ and Col Ⅳ in rats were detected，and protein expression of Beclin-1 and
LC3-Ⅱin liver tissue were also determined. mRNA and protein expression of Akt，AMPK，mTOR，p70S6K were detected in liver
tissues of rats. RESULTS：Compared with blank group，the structure of hepatic lobules in the model group was disordered，the
proliferation of fibrous tissue was obvious，and some pseudolobules were formed；the serum levels of HA，LN，PCⅢ and Col Ⅳ，
the protein expression of Beclin-1 and LC3-Ⅱ in liver tissue as well as mRNA and protein expression of Akt，AMPK，mTOR and
p70S6K were increased significantly （P＜0.01）. Compared with model group，the liver injury of rats in FRG groups was
significantly relieved，and the levels of the above indexes in serum and liver tissue（except for LN and PCⅢ in FRG low-dose
group） were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS：FRG can improve hepatic fibrosis in rats，the
mechanism of which may be associated with down-regulating the expression of autophagy associated protein and Akt/AMPK/mTOR/
p70S6K signaling pathway related protein.
KEYWORDS Fupi rougan granule；Hepatic fibrosis；Autophagy；Akt/AMPK/mTOR/p70S6K signaling pathway；Rats

肝纤维化是由多种不同病因所致慢性肝损伤而引
Δ 基 金 项 目 ：国 家 自 然 科 学 基 金 资 助 项 目（No.81760865，
起的病理性修复过程，以细胞外基质（ECM）异常沉积为
No.81460726）；贵州省科技计划项目（No.黔科合LH字〔2017〕7141号）
特点，进一步可转变为肝硬化或肝癌 。研究表明，肝纤
[1]
＊主任医师，教授，硕士生导师，博士。研究方向：中西医结合防
治 消 化 系 统 疾 病 的 基 础 及 临 床 。 电 话 ：0851-85637044。 E-mail： 维化患者经过干预治疗后，可以得到缓解甚至恢复；若
[2]
407206115@qq.com 干预不及时，可进展为肝硬化，从而难以恢复 。因此，
中国药房 2021年第32卷第21期 China Pharmacy 2021 Vol. 32 No. 21 ·2587 ·