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1.江西中医药大学临床医学院,南昌 330004
2.黑龙江中医药大学基础医学院,哈尔滨 150040
3.江西中医药大学中医学院,南昌 330004
4.江西中医药大学针灸推拿学院,南昌 330004
Received:06 July 2024,
Revised:2024-11-05,
Accepted:29 November 2024,
Published:30 January 2025
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郝峰,李冀,杜菁,等.乌梅抗肝纤维化的作用及机制研究[J].中国药房,2025,36(02):172-178.
HAO Feng,LI Ji,DU Jing,et al.Effect and mechanism of Prunus mume against hepatic fibrosis[J].ZHONGGUO YAOFANG,2025,36(02):172-178.
郝峰,李冀,杜菁,等.乌梅抗肝纤维化的作用及机制研究[J].中国药房,2025,36(02):172-178. DOI: 10.6039/j.issn.1001-0408.2025.02.07.
HAO Feng,LI Ji,DU Jing,et al.Effect and mechanism of Prunus mume against hepatic fibrosis[J].ZHONGGUO YAOFANG,2025,36(02):172-178. DOI: 10.6039/j.issn.1001-0408.2025.02.07.
目的
2
探讨乌梅抗肝纤维化(HF)的作用及机制。
方法
2
将雄性SD大鼠随机分为正常对照组(
n
=10)与造模组(
n
=50),造模组大鼠以四氯化碳诱导建立HF模型。将成模大鼠分为模型组(生理盐水)、阳性对照药组[秋水仙碱,0.09 mg/(kg·d)
]
及乌梅低、中、高剂量组[1.35、2.70、5.40 g/(kg·d)
]
,每组9只。大鼠每天灌胃相应药物/生理盐水1次,持续8周。末次给药后,计算大鼠肝脏指数,检测其肝功能指标、肝纤维化四项、氧化应激指标及炎症因子水平,采用苏木精-伊红(HE)染色法观察大鼠肝组织病理改变、Masson染色法观察大鼠HF程度、透射电镜法观察大鼠肝组织超微结构、TUNEL染色法检测大鼠肝细胞凋亡水平,并采用Western blot法检测大鼠肝组织中转化生长因子β
1
(TGF-β
1
)、血小板源性生长因子(PDGF)蛋白的表达。
结果
2
与正常对照组相比,模型组大鼠丙氨酸转氨酶、碱性磷酸酶、天冬氨酸转氨酶、总胆红素、丙二醛、Ⅲ型前胶原蛋白、Ⅳ型前胶原酶、层粘连蛋白、透明质酸、白细胞介素6、肿瘤坏死因子α水平和TGF-β
1
、PDGF蛋白表达水平均显著升高(
P
<0.01),超氧化物歧化酶、谷胱甘肽过氧化酶水平均显著降低(
P
<0.01);HE、Masson染色及透射电镜观察结果均提示模型组大鼠出现了明显的HF特征。与模型组比较,乌梅各剂量组大鼠上述指标均有不同程度改善,其中乌梅中、高剂量组大鼠上述指标均被显著逆转(
P
<0.05或
P
<0.01)。
结论
2
乌梅具有抗HF的作用,该作用可能是通过抗氧化、抗炎、减少胶原产生、抑制PDGF表达及调控TGF-β
1
信号通路等机制实现的。
OBJECTIVE
2
To explore the effect and mechanism of
Prunus mume
against hepatic fibrosis (HF).
METHODS
2
Male SD rats were randomly divided into normal control group (
n
=10) and modeling group (
n
=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)
]
, and
P. mume
low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)
]
, with 9 rats in each group. They were
given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β
1
(TGF-β
1
) and platelet-derived growth factor (PDGF) in liver tissue of rats.
RESULTS
2
Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β
1
and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (
P
<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in
P. mume
groups, and the above indicators of rats in
P. mume
medium-dose and high-dose groups were reversed significantly (
P
<0.05 or
P
<0.01).
CONCLUSIONS
2
P. mume
has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and re
gulation of TGF-β
1
signaling pathway.
LI M , WANG Z Q , ZHANG L , et al . Burden of cirrhosis and other chronic liver diseases caused by specific etiologies in China,1990-2016:findings from the global burden of disease study 2016 [J ] . Biomed Environ Sci , 2020 , 33 ( 1 ): 1 - 10 .
DAMIRIS K , TAFESH Z H , PYRSOPOULOS N . Efficacy and safety of anti-hepatic fibrosis drugs [J ] . World J Gastroentero , 2020 , 26 ( 41 ): 6304 - 6321 .
韦柳婷 , 高松林 , 吴凡 , 等 . 专利中药复方治疗肝纤维化的用药规律及机制研究 [J ] . 科学技术与工程 , 2024 , 24 ( 8 ): 3133 - 3144 .
WEI L T , GAO S L , WU F , et al . Medication regularity and mechanism of patented Chinese herbal compounds in treating hepatic fibrosis [J ] . Sci Technol Eng , 2024 , 24 ( 8 ): 3133 - 3144 .
张保伟 , 李爱峰 , 赵志敏 . 乌梅丸对免疫损伤性肝纤维化大鼠肝组织细胞因子TGF-β 1 及其mRNA的影响 [J ] . 中国中医急症 , 2007 ( 5 ): 585 - 586 .
ZHANG B W , LI A F , ZHAO Z M . The effects of Wumei pill on the expression TGF-β 1 and the mRNA in liver tissue of immunity-damaged liver fibrosis rats [J ] . J Emerg Tradit Chin Med , 2007 ( 5 ): 585 - 586 .
徐海龙 , 门科丽 , 潘林康 . 刘兴山教授运用乌梅丸治验 [J ] . 中医研究 , 2021 , 34 ( 1 ): 62 - 65 .
XU H L , MEN K L , PAN L K . Professor Liu Xingshan’s experience in treating Mume Fructus pill [J ] . Tradit Chin Med Res , 2021 , 34 ( 1 ): 62 - 65 .
杨亚湉 , 王瑞 , 钱程程 , 等 . 乌梅化学成分、药理作用研究进展及质量标志物预测 [J ] . 中成药 , 2023 , 45 ( 5 ): 1583 - 1588 .
YANG Y T , WANG R , QIAN C C , et al . Research pro- gress on chemical constituents and pharmacological effects of Mume Fructus and prediction of quality markers [J ] . Chin Tradit Pat Med , 2023 , 45 ( 5 ): 1583 - 1588 .
李燕 , 赖泳 . 炎症细胞和细胞因子在肝纤维化中的作用研究进展 [J ] . 中国医院药学杂志 , 2018 , 38 ( 18 ): 1980 - 1984 .
LI Y , LAI Y . Research progress on the roles of inflam-matory cells and cytokines in liver fibrosis [J ] . Chin J Hosp Pharm , 2018 , 38 ( 18 ): 1980 - 1984 .
梁文杰 , 陈晶 , 杜雅菊 . 参与肝纤维化形成的细胞和细胞因子的新进展 [J ] . 胃肠病学和肝病学杂志 , 2017 , 26 ( 5 ): 581 - 584 .
LIANG W J , CHEN J , DU Y J . New progress of the cells and cytokines involved in the formation of liver fibrosis [J ] . Chin J Gastroenterol Hepatol , 2017 , 26 ( 5 ): 581 - 584 .
YANG C Q , ZEISBERG M , MOSTERMAN B , et al . Liver fibrosis:insights into migration of hepatic stellate cells in response to extracellular matrix and growth factors [J ] . Gastroenterology , 2003 , 124 ( 1 ): 147 - 159 .
李高辉 , 吕文良 , 闫暾 , 等 . 四氯化碳致大鼠肝纤维化动物模型的文献再评价 [J ] . 实验动物科学 , 2021 , 38 ( 3 ): 39 - 46 .
LI G H , LYU W L , YAN T , et al . Re-evaluation of literature on rat liver fibrosis animal model induced by carbon tetrachloride [J ] . Lab Anim Sci , 2021 , 38 ( 3 ): 39 - 46 .
王颖 , 赵冠宇 , 薛淑萍 , 等 . 乌梅丸及其类方治疗胃肠疾病的临床与基础研究进展 [J ] . 中药药理与临床 , 2023 , 39 ( 3 ): 122 - 128 .
WANG Y , ZHAO G Y , XUE S P , et al . Mume Fructus wan and its similar prescriptions in the treatment of gastrointestinal diseases [J ] . Pharmacol Clin Chin Mater Med , 2023 , 39 ( 3 ): 122 - 128 .
章波 , 麦琬婷 , 檀燕君 , 等 . 秋水仙碱治疗肝纤维化的网络药理学研究 [J ] . 广西医科大学学报 , 2020 , 37 ( 3 ): 372 - 379 .
ZHANG B , MAI W T , TAN Y J , et al . A network pharmacological study of colchicine in the treatment of liver fibrosis [J ] . J Guangxi Med Univ , 2020 , 37 ( 3 ): 372 - 379 .
田甜 , 郑璐 , 汤雷 , 等 . 肝纤维化大鼠肝脏中组蛋白修饰水平的变化 [J ] . 中国病理生理杂志 , 2019 , 35 ( 3 ): 554 - 558 .
TIAN T , ZHENG L , TANG L , et al . Changes of histone modification levels in rats with liver fibrosis [J ] . Chin J Pathophysiol , 2019 , 35 ( 3 ): 554 - 558 .
付月月 , 朱兰平 , 张国梁 , 等 . 夏枯草硫酸多糖对CCl 4 致大鼠肝纤维化及TGF-β 1 诱导的大鼠肝星状细胞活化的影响 [J ] . 中国实验方剂学杂志 , 2018 , 24 ( 14 ): 147 - 152 .
FU Y Y , ZHU L P , ZHANG G L , et al . Effect of Prunellae Spica sulfated polysaccharide on carbon tetrachloride(CCl 4 )-induced hepatic fibrosis and activation of hepatic stellate cell induced by TGF-β 1 [J ] . Chin J Exp Tradit Med Formulae , 2018 , 24 ( 14 ): 147 - 152 .
ZHANG K , ZHANG M X , YAO Q B , et al . The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition [J ] . Theranostics , 2019 , 9 ( 25 ): 7566 - 7582 .
LIAO Z Z , ZHANG J Y , LIU B , et al . Polysaccharide from okra [ Abelmoschus esculentus (L.) Moench ] improves antioxidant capacity via PI3K/AKT pathways and Nrf2 translocation in a type 2 diabetes model [J ] . Mo- lecules , 2019 , 24 ( 10 ): 1906 .
陈秀梅 , 王英杰 , 赵成周 , 等 . 三味甘露对大鼠肝纤维化的改善作用及机制 [J ] . 中国药房 , 2024 , 35 ( 6 ): 707 - 711 .
CHEN X M , WANG Y J , ZHAO C Z , et al . Ameliorative effect and mechanism of Sanwei ganlu on hepatic fibrosis in rats [J ] . China Pharm , 2024 , 35 ( 6 ): 707 - 711 .
MASSAGUÉ J . TGF-β signalling in context [J ] . Nat Rev Mol Cell Biol , 2012 , 13 ( 10 ): 616 - 630 .
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