Moustafa Enas M, Moawed Fatma S M, Abdel-Hamid Gehan R
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.
Dose Response. 2020 Oct 30;18(4):1559325820970810. doi: 10.1177/1559325820970810. eCollection 2020 Oct-Dec.
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.
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.
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.
The potent bioactive therapeutic Icariin combined with MSCs induces a significantly greater improvement, compared to each therapy alone.
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。
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。
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。
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。
