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五味子乙素联合桔梗皂苷D通过抑制JAK2/STAT6通路调控巨噬细胞M1/M2极化改善肺纤维化

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中草药 | 药理与临床 2026,57(3): 968-980

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中草药 |药理与临床 2026 , 57 (3) : 968 -980

五味子乙素联合桔梗皂苷D通过抑制JAK2/STAT6通路调控巨噬细胞M1/M2极化改善肺纤维化

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孙梦迪¹, 孙志运¹, 卢芳¹, 于栋华¹, 王宇¹, 陈平平¹, 刘树民¹

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通讯作者:

刘树民

作者简介:

孙梦迪: 孙梦迪，博士研究生，研究方向为中药药性理论及药效物质基础。E-mail:sunmengdi1209@outlook.com

Schisandrin B combined with platycodin D ameliorates pulmonary fibrosis by regulating macrophage M1/M2 polarization via inhibition of JAK2/STAT6 pathway

SUN Mengdi, SUN Zhiyun, LU Fang, YU Donghua, WANG Yu, CHEN Pingping, LIU Shumin

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doi: 10.7501/j.issn.0253-2670.2026.03.015

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目的探讨五味子乙素（schisandrin B，Sch B）与桔梗皂苷D（platycodin D，PD）配伍对肺纤维化的改善作用，并研究其是否通过抑制Janus激酶（Janus kinase 2，JAK2）/信号转导与转录激活因子6（signal transducer and activator of transcription 6，STAT6）通路、调控巨噬细胞M1/M2极化平衡发挥作用。方法建立博来霉素诱导的大鼠肺纤维化模型，随机分为对照组、模型组、泼尼松（5 mg/kg）组、Sch B（10 mg/kg）组、PD（20 mg/kg）组和Sch B＋PD组，每组8只。给药28 d后，检测肺脏系数；采用苏木素-伊红（hematoxylin-eosin，HE）、Masson、天狼星红染色观察肺组织病理变化；检测支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）中白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）及肺组织羟脯氨酸（hydroxyproline，Hyp）水平；免疫荧光法检测肺组织α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、上皮钙黏蛋白（E-cadherin）表达；qRT-PCR检测肺组织M1/M2巨噬细胞标志物[诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）、TNF-α、IL-1β、白细胞分化抗原206（cluster of differentiation 206，CD206）、精氨酸酶1（arginase 1，Arg1）、IL-10]mRNA表达；Western blotting检测肺组织JAK2/STAT6通路相关蛋白表达。体外实验中，利用IL-4/IL-13诱导的巨噬细胞M2极化模型，验证Sch B与PD配伍对JAK2/STAT6通路的作用。结果与对照组比较，模型组大鼠肺脏系数显著升高（P＜0.01），肺泡内有大量炎性细胞浸润，肺泡膈断裂增多，肺泡破坏严重，BALF中IL-1β、TNF-α、IL-6和肺组织Hyp水平显著升高（P＜0.01）；肺组织α-SMA表达显著升高（P＜0.01），E-cadherin表达显著降低（P＜0.01）；肺组织iNOS、TNF-α、IL-1β、CD206、Arg1 mRNA表达水平显著升高（P＜0.01），IL-10 mRNA表达水平显著降低（P＜0.01）；肺组织JAK2、p-STAT6/STAT6蛋白表达水平显著升高（P＜0.01）。与模型组比较，Sch B与PD配伍能显著降低大鼠肺脏系数（P＜0.01），改善肺纤维化病理损伤，抑制炎症因子释放和肺组织Hyp水平（P＜0.01），减少α-SMA表达（P＜0.01），并部分恢复E-cadherin表达（P＜0.01），显著下调肺组织iNOS、TNF-α、IL-1β、CD206、Arg1 mRNA表达（P＜0.01），上调IL-10 mRNA表达（P＜0.01），并抑制JAK2和p-STAT6/STAT6蛋白表达（P＜0.01）。体外实验结果显示，与对照组比较，模型组CD206、Arg1 mRNA表达水平显著升高（P＜0.01），JAK2、p-STAT6/STAT6蛋白表达显著上调（P＜0.01）；与模型组比较，Sch B与PD配伍能显著抑制M2极化标志物CD206、Arg1表达（P＜0.01），下调JAK2和p-STAT6/STAT6蛋白表达（P＜0.01）。与单独给药组比较，Sch B与PD配伍效果更佳（P＜0.05、0.01）。结论 Sch B与PD配伍能够协同缓解肺纤维化，其机制可能与抑制JAK2/STAT6通路活化，从而纠正M1/M2巨噬细胞极化失衡有关。

关键词

五味子乙素 / 桔梗皂苷D / 肺纤维化 / 巨噬细胞极化 / JAK/STAT通路

Abstract

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Objective To investigate the ameliorative effect of combination of schisandrin B (Sch B) and platycodin D (PD) on pulmonary fibrosis, and explore whether it acts by inhibiting Janus kinase 2 (JAK2)/signal transducer and activator of transcription 6 (STAT6) pathway and regulating the balance of macrophage M1/M2 polarization. Methods A rat model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. The rats were randomly divided into control group, model group, prednisone (5 mg/kg) group, Sch B (10 mg/kg) group, PD (20 mg/kg) group and Sch B + PD group, with eight rats in each group. After 28 d of administration, lung index was measured. Pathological changes in lung tissue were observed using hematoxylin-eosin (HE), Masson and Sirius red staining. Levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), as well as hydroxyproline (Hyp) level in lung tissue were detected. Expressions of α-smooth muscle actin (α-SMA) and E-cadherin in lung tissue were assessed by immunofluorescence. The mRNA expressions of M1/M2 macrophage markers [inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, cluster of differentiation 206 (CD206), arginase 1 (Arg1) and IL-10] in lung tissue were measured by qRT-PCR. The expressions of JAK2/STAT6 pathway related proteins in lung tissue was determined by Western blotting. In vitro experiments, the effect of Sch B combined with PD on JAK2/STAT6 pathway were validated using an IL-4/IL-13-induced macrophage M2 polarization model. Results Compared with control group, lung index of rats in model group was significantly increased (P < 0.01), with a large amount of inflammatory cell infiltration in alveoli, increased alveolar diaphragmatic rupture and severe alveolar damage, levels of IL-1β, TNF-α, IL-6 in BALF and Hyp in lung tissue were significantly increased (P < 0.01); The expression of α-SMA in lung tissue was significantly increased (P < 0.01), while the expression of E-cadherin was significantly decreased (P < 0.01); The expression levels of iNOS, TNF-α, IL-1β, CD206 and Arg1 mRNA in lung tissue were significantly increased (P < 0.01), while the expression level of IL-10 mRNA was significantly decreased (P < 0.01); The expression levels of JAK2 and p-STAT6/STAT6 proteins in lung tissue were significantly increased (P < 0.01). Compared with model group, the combination of Sch B and PD could significantly reduce the lung index of rats (P < 0.01), improve pulmonary fibrosis pathological damage, inhibit the release of inflammatory factors and Hyp level in lung tissue (P < 0.01), reduce α-SMA expression (P < 0.01), partially restore E-cadherin expression (P < 0.01), significantly down-regulate iNOS, TNF-α, IL-1β, CD206, Arg1 mRNA expressions in lung tissue (P < 0.01), up-regulate IL-10 mRNA expression (P < 0.01), inhibit JAK2 and p-STAT6/STAT6 protein expressions (P < 0.01). The in vitro experimental results showed that compared with control group, the expression levels of CD206 and Arg1 mRNA in model group were significantly increased (P < 0.01), and the expressions of JAK2 and p-STAT6/STAT6 proteins were significantly up-regulated (P < 0.01); Compared with model group, the combination of Sch B and PD significantly inhibited the expressions of M2 polarization markers CD206 and Arg1 (P < 0.01), and down-regulated the expressions of JAK2 and p-STAT6/STAT6 proteins (P < 0.01). Compared with the group treated alone, the combination of Sch B and PD showed better efficacy (P < 0.05, 0.01). Conclusion The combination of Sch B and PD could synergistically alleviate pulmonary fibrosis, and its mechanism may be related to inhibiting the activation of JAK2/STAT6 pathway, thereby correcting the imbalance of M1/M2 macrophage polarization.

Key words

schisandrin B / platycodin D / pulmonary fibrosis / macrophage polarization / JAK/STAT pathway

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孙梦迪, 孙志运, 卢芳, 于栋华, 王宇, 陈平平, 刘树民. 五味子乙素联合桔梗皂苷D通过抑制JAK2/STAT6通路调控巨噬细胞M1/M2极化改善肺纤维化. 中草药, 2026 , 57 (3) : 968 -980 . DOI: 10.7501/j.issn.0253-2670.2026.03.015

SUN Mengdi, SUN Zhiyun, LU Fang, YU Donghua, WANG Yu, CHEN Pingping, LIU Shumin. Schisandrin B combined with platycodin D ameliorates pulmonary fibrosis by regulating macrophage M1/M2 polarization via inhibition of JAK2/STAT6 pathway[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (3) : 968 -980 . DOI: 10.7501/j.issn.0253-2670.2026.03.015

基金

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黑龙江省自然科学基金重点项目(ZD2020H006)

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2026年第57卷第3期

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doi: 10.7501/j.issn.0253-2670.2026.03.015

接收时间：2025-11-01
首发时间：2026-09-08

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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