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淫羊藿苷促进L-精氨酸/辐射诱导的大鼠慢性胰腺炎中干细胞再生及腺泡细胞修复

Icariin Promote Stem Cells Regeneration and Repair Acinar Cells in L-arginine / Radiation -Inducing Chronic Pancreatitis in Rats.

作者信息

Moustafa Enas M, Moawed Fatma S M, Abdel-Hamid Gehan R

机构信息

Department of Radiation Biology, Cairo, Egypt.

Department of Health Radiation Research, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.

出版信息

Dose Response. 2020 Oct 30;18(4):1559325820970810. doi: 10.1177/1559325820970810. eCollection 2020 Oct-Dec.

Abstract

OBJECTIVE

Chronic Pancreatitis (CP) is a multifactorial disease. It was characterized by severe inflammation and acinar cell destruction. Thus, the present study was initiated to evaluating the ability of bone marrow-based mesenchymal stem cell (MSCs) combined with Icariin to restore and regenerate acinar cells in the pancreas of rats suffering chronic pancreatitis.

METHODS

Chronic pancreatitis was induced in rats via both L-arginine plus radiation, repeated L-arginine injection (2.5g/Kg body-weight, 1, 4,7,10,13,16,19 days), then, on day 21, rats were exposed to a single dose of gamma-radiation (6 Gy), which exacerbate injury of pancreatic acinar cells. One day after irradiation, rats were treated with either MSCs (1 × 10 /rat, once, tail vein injection) labeled PKH26 fluorescent linker dye and/or Icariin (100 mg/Kg, daily, orally) for 8 weeks.

RESULTS

Icariin promotes MSCs proliferation boosting its productivity . MSCs, and/or icariin treatments has regulated molecular factors TGF-β/PDGF and promoted the regeneration of pancreatic tissues by releasing PDX-1 and MafA involved in the recruitment of stem/progenitor cell in the tissue, and confirmed by histopathological examination. Moreover, a significant decrease in IL-8 and TNF-α cytokines with significant amelioration of myeloperoxidase activity were noted. As well as, reduction in MCP-1 and collagen type-1 levels along with Hedgehog signaling down-regulating expression in such cells, Patched-1, Smoothened, and GLi-1.

CONCLUSION

The potent bioactive therapeutic Icariin combined with MSCs induces a significantly greater improvement, compared to each therapy alone.

摘要

目的

慢性胰腺炎(CP)是一种多因素疾病。其特征为严重炎症和腺泡细胞破坏。因此,本研究旨在评估基于骨髓的间充质干细胞(MSCs)联合淫羊藿苷恢复和再生慢性胰腺炎大鼠胰腺腺泡细胞的能力。

方法

通过L-精氨酸加辐射、重复注射L-精氨酸(2.5g/千克体重,第1、4、7、10、13、16、19天)诱导大鼠患慢性胰腺炎,然后在第21天,大鼠接受单剂量γ辐射(6 Gy),这加剧了胰腺腺泡细胞的损伤。辐射后一天,大鼠接受用PKH26荧光连接染料标记的MSCs(1×10⁶/只大鼠,单次,尾静脉注射)和/或淫羊藿苷(100mg/千克,每日,口服)治疗8周。

结果

淫羊藿苷促进MSCs增殖,提高其活性。MSCs和/或淫羊藿苷治疗调节了分子因子TGF-β/PDGF,并通过释放参与组织中干细胞/祖细胞募集的PDX-1和MafA促进胰腺组织再生,组织病理学检查证实了这一点。此外,还注意到IL-8和TNF-α细胞因子显著降低,髓过氧化物酶活性显著改善。同时,MCP-1和I型胶原水平降低,以及刺猬信号通路在这些细胞中Patched-1、Smoothened和Gli-1的表达下调。

结论

与单独的每种疗法相比,强效生物活性治疗药物淫羊藿苷联合MSCs诱导的改善显著更大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f0/7607780/e089e7c8d43f/10.1177_1559325820970810-fig1.jpg

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