桦褐孔菌多糖对慢性非细菌性前列腺炎的作用及对Th17/Treg免疫失衡的影响

doi:10.5246/jcps.2025.02.010

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (2): 126-134.DOI: 10.5246/jcps.2025.02.010

桦褐孔菌多糖对慢性非细菌性前列腺炎的作用及对Th17/Treg免疫失衡的影响

赵晓茹, 韩立华, 郝渺, 彭莉莉, 原红霞^*(), 李青山^*()

山西中医药大学中药与食品工程学院基于炎性反应的重大疾病创新药物山西省重点实验室, 山西晋中 030619

收稿日期:2024-10-26 修回日期:2024-11-15 接受日期:2024-12-08 出版日期:2025-03-01 发布日期:2025-03-02
通讯作者: 原红霞, 李青山

Effect of inonotus obliquus polysaccharide on chronic nonbacterial prostatitis and its effect on Th17/Treg immune imbalance

Xiaoru Zhao, Lihua Han, Miao Hao, Lili Peng, Hongxia Yuan^*(), Qingshan Li^*()

Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, College of Traditional Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi, China

Received:2024-10-26 Revised:2024-11-15 Accepted:2024-12-08 Online:2025-03-01 Published:2025-03-02
Contact: Hongxia Yuan, Qingshan Li
Supported by:
Shanxi Province Traditional Chinese Medicine Administration Research Project (Grant No. 2022ZYYC094), Science and technology innovation project of universities in Shanxi Province (Grant No. 2022L342), Shanxi Leader Team of Medical Science & Technology Innovations (Grant No. 2020TD02), Discipline Construction Project of Chinese Medicine Chemistry (Grant No. 2024XKJS-25).

摘要/Abstract

摘要：

本研究旨在观察桦褐孔菌多糖(IOP)对慢性非细菌性前列腺炎(CNP)的治疗作用及对辅助性T细胞(Th17)和调节性T细胞(Treg)免疫失衡的影响。将注射消痔灵注射液建立的CNP大鼠模型随机分为模型组、舍尼通(40 mg/kg)组及IOP低剂量组(35 mg/kg)、中剂量组(70 mg/kg)以及高剂量组(140 mg/kg), 同部位注射等体积生理盐水作为对照组。以前列腺湿重和体质量作为计算前列腺指数的依据。ELISA法检测血清前列腺特异性抗原(PSA)水平, HE染色检测前列腺组织病理学。Western blot检测大鼠前列腺组织中Foxp3、ROR-γt和STAT3蛋白的表达。流式细胞术检测脾脏中浸润的Th17和Treg细胞水平。结果显示, IOP治疗可显著降低前列腺指数和血清PSA水平, 减轻CNP诱导的前列腺组织病理损伤。与模型组相比, 各给药组前列腺组织中IL-6、IL-17、IL-21、IL-23、ROR-γt和STAT3 mRNA水平及ROR-γt和STAT3蛋白表达水平均有不同程度的降低, IL-10、TGF-β和Foxp3 mRNA水平及Foxp3蛋白表达水平均有不同程度的升高。流式细胞术分析进一步证明IOP治疗调节了CNP大鼠脾脏中Th17和Treg细胞之间的平衡。研究首次阐明了IOP通过调控Th17/Treg平衡对CNP具有显著的治疗作用, 为IOP治疗CNP的潜力提供了证据。

关键词: 桦褐孔菌多糖, 慢性非细菌性前列腺炎, Th17, Treg, Th17/Treg平衡

Abstract:

The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide (IOP) on chronic nonbacterial prostatitis (CNP) and its effect on the helper T cells (Th17) and regulatory T cells (Treg) immune imbalance. The CNP rat models established by injecting Xiaozhiling injection were randomly divided into the model group, cernilton (40 mg/kg, i.g.) group and low-dose (35 mg/kg, i.g.), medium-dose (70 mg/kg, i.g.) and high-dose (140 mg/kg, i.g.) groups, with the same volume of saline injected into the same site as the control group. The prostate’s wet weight and body mass served as the basis for calculating the prostate index. The serum level of prostate-specific antigen (PSA) was detected by ELISA and the histopathology of prostate tissue was detected by HE staining. The protein expression of Foxp3, ROR-γt and STAT3 in rat prostatic tissue was determined by Western blot. The levels of Th17 and Treg cells infiltrated into the spleen were measured by flow cytometry. The results showed that treatment with IOP significantly reduced the levels of prostate index and serum PSA, and attenuated the pathological injury of the prostate tissue induced by CNP. With respect to samples induced by CNP alone, IOP treatment repressed the increased mRNA levels of IL-6, IL-17, IL-21, IL-23, ROR-γt and STAT3 in prostate tissue, while increasing the mRNA levels of IL-10, TGF-β and Foxp3 in prostate tissue. Meanwhile, IOP treatment attenuated the upregulation of the protein expression levels of ROR-γt and STAT3 in prostate tissue. Additionally, the protein expression of Foxp3 in prostate tissue was increased in the IOP-treated group. Flow cytometry analysis further demonstrated that IOP treatment regulated the balance between Th17 and Treg cells in the spleen in rat with CNP. Our study is the first to elucidate that IOP has significant therapeutic effects on CNP through regulation of Th17/Treg balance. Collectively, the study provides evidence for the potential of IOP to treat CNP.

Key words: Inonotus obliquus polysaccharide, Chronic nonbacterial prostatitis, Th17, Treg, Th17/Treg balance

Supporting:

赵晓茹, 韩立华, 郝渺, 彭莉莉, 原红霞, 李青山. 桦褐孔菌多糖对慢性非细菌性前列腺炎的作用及对Th17/Treg免疫失衡的影响[J]. 中国药学(英文版), 2025, 34(2): 126-134.

Xiaoru Zhao, Lihua Han, Miao Hao, Lili Peng, Hongxia Yuan, Qingshan Li. Effect of inonotus obliquus polysaccharide on chronic nonbacterial prostatitis and its effect on Th17/Treg immune imbalance[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(2): 126-134.

图/表 7

Table 1. Primers sequence information.

Figure 1. Effect of IOP on prostate index of CNP rats. Data are means ± SD, n = 8. ##P < 0.01 vs. control group; **P < 0.01 vs. model group.

Figure 2. Effect of IOP on pathological morphologic changes of prostate tissue in CNP rats.

Figure 3. Effect of IOP on serum PSA expression in CNP rats. The expression of PSA in serum was detected using ELISA analysis. Data are presented as means ± SD, n = 8. ##P < 0.01 vs. control group; *P < 0.05, **P < 0.01 vs. model group.

Figure 4. Effect of IOP on Th17/Treg balance in spleen of CNP rats. (A) The expression of Th17 cells in spleen were detected using flow cytometry analysis. (B) The expression of Treg cells in spleen were detected using flow cytometry analysis. (C) Proportion of Th17 cells in spleen. (D) Proportion of Treg cells in spleen. (E) Proportion of Th17/Treg cells in spleen. Data are presented as means ± SD, n = 8. ##P < 0.01 vs. control group; **P < 0.01 vs. model group, &P < 0.05, &&P < 0.01 vs. cernilton.

Figure 5. Effect of IOP on mRNA expression of Th17/Treg balance related genes in prostate tissues of CNP rats. (A, B) The expression of IL-21, IL-23, IL-6, IL-17, ROR-γt and STAT3 mRNA in prostate tissue were detected using qRT-PCR analysis. (C) The expression of IL-10, Foxp3 and TGF-β mRNA in prostate tissue were detected using qRT-PCR analysis. Data are presented as means ± SD, n = 8. ##P < 0.01 vs. control group; *P < 0.05, **P < 0.01 vs. model group, &&P＜0.01 vs. cernilton.

Figure 6. Expression of IOP on Th17/Treg balance in prostate tissue of CNP rats. (A, B) The expression of Foxp3, ROR-γt and STAT3 protein in prostate tissue were detected using Western blot analysis. Data are presented as means ± SD, n = 5. ##P < 0.01 vs. control group; *P < 0.05, **P < 0.01 vs. model group, &P < 0.05, &&P < 0.01 vs. cernilton.

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桦褐孔菌多糖对慢性非细菌性前列腺炎的作用及对Th17/Treg免疫失衡的影响

Effect of inonotus obliquus polysaccharide on chronic nonbacterial prostatitis and its effect on Th17/Treg immune imbalance

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