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中药有效成分及方剂干预胰腺星状细胞治疗慢性胰腺炎的作用机制
DOI: 10.12449/JCH250429
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：程汝阳负责课题设计，资料分析，撰写论文；宋蔚宁负责论文修改；蒋鑫、王业豪、刘林参与收集数据；卢芳、刘树民负责拟定写作思路，指导撰写文章并最后定稿。
The mechanism of effective traditional Chinese medicine components and prescriptions in treatment of chronic pancreatitis by intervening against pancreatic stellate cells
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摘要: 慢性胰腺炎（CP）是一种以炎症反复发作和胰腺组织受到进行性损伤为特征的慢性疾病，其病情恶化时还会增加CP患者胰腺癌的发生风险，严重威胁着CP患者的身体健康。近些年，CP发病机制的研究多集中在胰腺星状细胞（PSC）的激活及在胰腺纤维化中的作用。本文详细叙述了PSC在CP中的作用机制，总结了中药有效成分及方剂干预PSC治疗CP的研究现状，指出了中药有效成分及方剂治疗CP的研究方向，为日后CP患者的临床治疗提供参考。Abstract: Chronic pancreatitis （CP） is a chronic disease characterized by recurrent inflammation and progressive damage to pancreatic tissue， and its deterioration may increase the risk of pancreatic cancer in patients with CP， which seriously threatens the health of patients with CP. In recent years， studies on the pathogenesis of CP have mostly focused on the activation of pancreatic stellate cells （PSCs） and its role in pancreatic fibrosis. This article elaborates on the mechanism of action of PSCs in CP， summarizes the current status of research on effective traditional Chinese medicine components and prescriptions for intervention of PSCs in the treatment of chronic CP， and proposes the future research directions for effective traditional Chinese medicine components and prescriptions， so as to provide a reference for the clinical treatment of CP patients in the future.
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注： FN，纤维连接蛋白；COL1A1，Ⅰ型胶原；MDA，丙二醛；SOD，超氧化物歧化酶；GSH，谷胱甘肽。
图 1 中药有效成分干预PSC活化治疗CP的作用机制
Figure 1. Mechanism of intervention of active ingredients of traditional Chinese medicine in the activation of PSCs in the treatment of CP
表 1 中药有效成分治疗CP的作用机制
Table 1. Mechanism of action of active ingredients of traditional Chinese medicine in the treatment of chronic pancreatitis
药理作用 中药有效成分 模型 作用机制 抗炎/抑制纤维化 异甘草素［10］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP；人源PSC；RAW 264.7巨噬细胞 NF-κB↓ 反式白藜芦醇［11］ 大鼠LTC-14 PSC NF-κB↓ 黄连素［12］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP；RAW 264.7巨噬细胞 TGF-β/Smad↓ 胡椒碱［13］、秦皮水提物［14］、儿茶素水合物［15］ 腹腔内注射雨蛙素诱导C57BL/6小鼠CP；小鼠PSC TGF-β/Smad↓ 柴胡皂苷D［16］ 尾静脉注射DBTC诱导Wistar大鼠；AR42J腺泡细胞；大鼠PSC JNK、P38-MAPK、ERK1/2↓；MMP/TIMP↑ 葛根素［17］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP；人源PSC JNK、P38-MAPK、ERK1/2↓；MMP/TIMP↑ 黄芩苷［18-19］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP；小鼠巨噬细胞；小鼠PSC p-TAK1↓ 番石榴叶总黄酮［20-21］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP； P2X7R、NLRP3↓ 氧化苦参碱［22］ 大鼠LTC-14 PSC miRNA-211-5p↑ 抑制氧化应激 白藜芦醇［23］ 人源PSC；人胰腺癌细胞系Panc-1 miRNA-21、ROS↓ 鸢尾素［24］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP；人源PSC MDA、SOD、GSH↓ 橄榄叶提取物［25］ 腹腔注射L-精氨酸诱导Sprague-Dawley大鼠CP MDA、SOD、GSH↓ 抑制自噬 柴胡皂苷D［26］ 尾静脉注射DBTC诱导Wistar大鼠CP；AR42J腺泡细胞；大鼠PSC mTOR↑ 柴胡皂苷A［27］ 大鼠PSC mTOR↑ 改善肠道菌群 桦褐孔菌多糖［28］ 腹腔注射DDC诱导小鼠CP 放线杆菌、蓝藻、变形杆菌↓ 灵芝多糖［29］ 腹腔注射DDC诱导小鼠CP 罗氏菌属、乳酸杆菌属↑ 注：DBTC，二氯二丁基酯；MDA，丙二醛；SOD，超氧化物歧化酶；GSH，谷胱甘肽；DDC，二乙基二硫代氨基甲酸钠；P2X7R，嘌呤能P2X7受体；JNK，c-Jun N末端激酶；ERK，细胞外信号调节激酶；MAPK，丝裂原活化蛋白激酶；p-TAK，磷酸化转化生长因子β活化酶1；MMP，基质金属蛋白酶；TIMP，金属蛋白酶组织抑制因子。
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表 2 中药方剂治疗CP的作用机制
Table 2. Mechanism of action of TCM compound in the treatment of chronic pancreatitis
药理作用 中药方剂 模型 作用机制 抑制纤维化 加味健脾疏肝通络方［42］ 尾静脉注射DBTC诱导SD大鼠CP ECM↓ 大柴胡汤［43-44］ 尾静脉注射DBTC诱导C57BL/6小鼠CP；腹腔注射L-精氨酸诱导C57BL/6小鼠CP ECM↓ 大黄丹参水煎液［45］ 腹腔注射DDC诱导Wistar大鼠CP ECM↓ 加味小柴胡汤［46］ 尾静脉注射DBTC诱导Wistar大鼠CP ECM↓ 抑制自噬 柴胡桂枝干姜汤［47］ 尾静脉注射DBTC诱导Wistar大鼠CP；大鼠PSC p-JNK、p-mTOR↑ 抗炎 小柴胡汤［48］ 腹腔注射雨蛙素诱导C57BL/6小鼠CP VD、VDR↑ 抑制氧化应激 大黄丹参汤［49］ 腹腔注射DDC诱导SD大鼠CP MMK-3/p38、Nrf2↑ 抑制内质网应激 胰泰方剂［50］ 腹腔注射L-精氨酸诱导SD大鼠CP CHOP、GRP78↑
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