中国临床药理学杂志

淫羊藿苷通过miRNA-98-5p介导AMPK/mTOR/ULK1信号通路调节免疫失耐受影响免疫性血小板减少症的研究

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李洁冰 ¹^,^2a , 吴静静 ³ , 胥晓琦 ³ , 张晓冬 ^2b

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(5): 678-685

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (5) : 678 -685

淫羊藿苷通过miRNA-98-5p介导AMPK/mTOR/ULK1信号通路调节免疫失耐受影响免疫性血小板减少症的研究

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李洁冰¹^,^2a, 吴静静³, 胥晓琦³, 张晓冬^2b

作者信息

^1.河南中医药大学儿科医学院，河南郑州 450000

^2a.南阳市第一人民医院儿二科，河南南阳 473000

^2b.南阳市第一人民医院血液科，河南南阳 473000

^3.河南中医药大学第一附属医院儿科，河南郑州 450000

通讯作者:

张晓冬，副主任医师 MP: 13937713145 E-mail: lijiebing_1994@163.com

作者简介:

李洁冰（1984-），女，副主任医师，主要从事中西医结合防治小儿肾病方面的临床工作和研究

Research of icariin in immune thrombocytopenia by regulating immune tolerance loss through the AMPK/mTOR/ULK1 signaling pathway mediated by miRNA-98-5p

Jie-bing LI¹^,^2a, Jing-jing WU³, Xiao-qi XU³, Xiao-dong ZHANG^2b

Affiliations

^1.School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China

^2a.Department of Pediatrics Ⅱ, Nanyang First People’s Hospital, Nanyang 473000, Henan Province, China

^2b.Department of Hematology, Nanyang First People’s Hospital, Nanyang 473000, Henan Province, China

^3.Department of Pediatrics, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine pediatrics, Zhengzhou 450000, Henan Province, China

出版时间: 2026-03-17 doi: 10.13699/j.cnki.1001-6821.2026.05.014

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摘要

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目的

探讨淫羊藿苷通过微小RNA（miRNA）-98-5p介导腺苷酸活化蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）/Unc-51样自噬激活激酶1（ULK1）信号通路调节免疫失耐受对免疫性血小板减少症（ITP）的作用及机制。

方法

小鼠腹腔注射豚鼠抗小鼠血小板血清构建ITP模型，另取12只正常小鼠为对照组，将造模成功的小鼠分为模型组、低剂量实验组、高剂量实验组和阳性药组。低、高剂量实验组和阳性药组分别在小鼠造模后灌胃1.25、5.00 mg·kg^-1淫羊藿苷及9.1 mg·kg^-1醋酸泼尼松。用全自动血液分析仪检测血小板（PLT）和血红蛋白（Hb）的水平；用酶联免疫吸附实验法检测血小板生成素（TPO）和炎症因子水平；用苏木素-伊红染色法检测脾组织病理损伤；用胸骨骨髓涂片法观察巨核细胞；用实时荧光定量聚合酶链反应法检测miRNA-98-5p表达水平；用蛋白质印迹法检测AMPK/mTOR/ULK1信号通路蛋白表达。

结果

对照组、模型组、低剂量实验组、高剂量实验组和阳性药组的PLT水平分别为（1 504.56±166.99）、（752.68±80.33）、（862.95±98.33）、（1 212.35±134.23）和（1 363.23±155.33）×10⁹·L^-1，Hb水平分别为（151.33±18.96）、（124.11±13.56）、（138.32±14.02）、（145.33±16.88）和（149.22±16.02）g·L^-1，TPO水平分别为（12.05±1.33）、（5.86±0.78）、（6.62±0.96）、（7.85±0.92）和（9.66±0.89）pg·mL^-1，白介素（IL）-6水平分别为（18.96±2.33）、（44.33±5.39）、（39.25±4.46）、（32.32±4.33）和（22.98±3.78）ng·L^-1，IL-10水平分别为（42.15±6.48）、（23.12±3.56）、（26.89±3.99）、（31.02±4.65）和（33.66±4.86）ng·L^-1，肿瘤坏死因子-α（TNF-α）水平分别为（31.02±4.65）、（77.36±8.98）、（67.65±7.88）、（60.52±7.34）和（40.56±5.99）ng·L^-1，干扰素-γ（IFN-γ）水平分别为（4.33±0.68）、（8.33±0.96）、（7.35±0.89）、（6.02±0.81）和（5.86±0.75）ng·L^-1，miRNA-98-5p相对表达水平分别为1.00±0.16、1.78±0.21、1.51±0.18、1.22±0.16和1.15±0.15，磷酸化（p）-AMPK/AMPK相对表达水平分别为1.00±0.14、1.81±0.28、1.60±0.19、1.31±0.16和1.25±0.21，p-mTOR/β-肌动蛋白（β-actin）相对表达水平分别为1.00±0.16、0.48±0.07、0.59±0.09、0.79±0.12和0.82±0.14，p-ULK1/β-actin相对表达水平分别为1.00±0.15、0.42±0.06、0.53±0.09、0.89±0.14和0.93±0.16，模型组上述指标与对照组比较，低、高剂量实验组和阳性药组上述指标与模型组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。

结论

淫羊藿苷通过下调miRNA-98-5p表达调控AMPK/mTOR/ULK1信号通路来调节ITP小鼠免疫失耐受，抑制细胞自噬，从而提升血小板水平。

关键词

淫羊藿苷 / 免疫性血小板减少症 / 免疫失耐受 / 微小RNA-98-5p / 腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白/Unc-51样自噬激活激酶1信号通路 / 自噬

Abstract

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Objective

To explore the mechanism of action by which icariin regulates the loss of immune tolerance to immune thrombocytopenia (ITP) through the microRNA (miRNA)-98-5p-mediated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like autophagy-activating kinase 1 (ULK1) signaling pathway.

Methods

The ITP model was established by intraperitoneal injection of guinea pig anti-mouse platelet serum into mice. Another 12 normal mice were taken as the control group. The mice with successful modeling were divided into model group, the experimental-low group, the experimental-high group and the positive drug group. The experimental-low and experimental-high groups and the positive drug group were gavaged with 1.25, 5.00 mg·kg^-1 icariin and 9.1 mg·kg^-1 prednisone acetate, respectively, after the mice were modeled. The levels of platelets (PLT) and hemoglobin (Hb) were detected by automatic blood analyzer; the levels of thrombopoietin (TPO) and inflammatory factors were detected by enzyme-linked immunosorbent assay; the pathological damage of spleen tissue was detected by hematoxylin-eosin staining; megakaryocytes were observed with sternum bone marrow smears; the relative expression level of miRNA-98-5p was detected by real-time fluorescence quantitative polymerase chain reaction; and the protein relative expression levels of the AMPK/mTOR/ULK1 signaling pathway was detected by Western blotting.

Results

The PLT levels in control group, model group, experimental-low group, experimental-high group and positive drug group were (1 504.56±166.99), (752.68±80.33), (862.95±98.33), (1 212.35±134.23) and (1 363.23±155.33)×10·L^-1, respectively; the Hb levels were (151.33±18.96), (124.11±13.56), (138.32±14.02), (145.33±16.88) and (149.22±16.02) g·L^-1, respectively; the TPO levels were (12.05±1.33), (5.86±0.78), (6.62±0.96), (7.85±0.92) and (9.66±0.89) pg·mL^-1, respectively; the levels of interleukin-6 (IL-6) were (18.96±2.33), (44.33±5.39), (39.25±4.46), (32.32±4.33) and (22.98±3.78) ng·L^-1, respectively; the levels of IL-10 were (42.15±6.48), (23.12±3.56), (26.89±3.99), (31.02±4.65) and (33.66±4.86) ng·L^-1, respectively; the levels of tumor necrosis factor-α(TNF-α) were (31.02±4.65), (77.36±8.98), (67.65±7.88), (60.52±7.34) and (40.56±5.99) ng·L^-1, respectively; the levels of interferon-gamma (IFN-γ) were (4.33±0.68), (8.33±0.96), (7.35±0.89), (6.02±0.81) and (5.86±0.75) ng·L^-1, respectively; the relative expression levels of miRNA-98-5p were 1.00±0.16, 1.78±0.21, 1.51±0.18, 1.22±0.16 and 1.15±0.15, respectively; the relative expression levels of phosphorylated (p)-AMPK/AMPK were 1.00±0.14, 1.81±0.28, 1.60±0.19, 1.31±0.16 and 1.25±0.21, respectively; the relative expression levels of p-mTOR/β-actin were 1.00±0.16, 0.48±0.07, 0.59±0.09, 0.79±0.12 and 0.82±0.14, respectively; the relative expression levels of p-ULK1/β-actin were 1.00±0.15, 0.42±0.06, 0.53±0.09, 0.89±0.14 and 0.93±0.16, respectively. There were statistically significant differences when comparing the above indicators of model group with those of control group, and also when comparing the above indicators of the experimental-low, experimental-high groups and positive drug group with those of model group (P<0.05, P<0.01, P<0.001).

Conclusion

Icariin regulates the loss of immune tolerance in rats with ITP, inhibits autophagy, and thus elevates platelet levels by down-regulating the expression of miRNA-98-5p and modulating the AMPK/mTOR/ULK1 signaling pathway.

Key words

icariin / immune thrombocytopenia / loss of immune tolerance / microRNA-98-5p / adenosine monophosphate-activated protein kinase/mammalian target of rapamycin/unc-51-like autophagy-activating kinase 1 signaling pathway / autophagy

引用本文

李洁冰, 吴静静, 胥晓琦, 张晓冬. 淫羊藿苷通过miRNA-98-5p介导AMPK/mTOR/ULK1信号通路调节免疫失耐受影响免疫性血小板减少症的研究. 中国临床药理学杂志, 2026 , 42 (5) : 678 -685 . DOI: 10.13699/j.cnki.1001-6821.2026.05.014

Jie-bing LI, Jing-jing WU, Xiao-qi XU, Xiao-dong ZHANG. Research of icariin in immune thrombocytopenia by regulating immune tolerance loss through the AMPK/mTOR/ULK1 signaling pathway mediated by miRNA-98-5p[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (5) : 678 -685 . DOI: 10.13699/j.cnki.1001-6821.2026.05.014

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2026年第42卷第5期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.05.014

接收时间：2025-06-20
首发时间：2026-08-06
出版时间：2026-03-17

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收稿日期：2025-06-20

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作者信息

^1.河南中医药大学儿科医学院，河南郑州 450000

^2a.南阳市第一人民医院儿二科，河南南阳 473000

^2b.南阳市第一人民医院血液科，河南南阳 473000

^3.河南中医药大学第一附属医院儿科，河南郑州 450000

通讯作者:

张晓冬，副主任医师 MP: 13937713145 E-mail: lijiebing_1994@163.com

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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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