Abdolmohammadi Kamal, Mahmoudi Tayebeh, Nojehdehi Shahrzad, Tayebi Lobat, Hashemi Seyed Mahmoud, Noorbakhsh Farshid, Abdollahi Alireza, Soleimani Masoud, Nikbin Behrouz, Nicknam Mohammad Hossein
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Adv Pharm Bull. 2020 Jun;10(2):297-306. doi: 10.34172/apb.2020.036. Epub 2020 Feb 18.
Acute pancreatitis (AP) is an inflammatory disorder distinguished by tissue injury and inflammation of the pancreas. Using paracrine potential of mesenchymal stem cells (MSCs) provides a useful clinical approach in treating inflammatory diseases. We investigated the therapeutic effects of adipose-derived MSC conditioned medium (CM) and hypoxia preconditioned adipose-derived MSC conditioned medium (HCM) in cerulein-induced AP in mice. AP was induced in C57BL/6 mice by intraperitoneal injection of cerulein (75 μg/ kg/h × 7 times). One hour following the last injection of cerulein, mice were treated with intraperitoneal injection of CM and HCM (500 µL/mice/30 min × 3 times). Twelve hours following the treatment, serum levels of amylase and lipase were measured. In addition, pancreas pathological changes, immunohistochemical examinations for evaluation of IL-6 expression and pancreatic myeloperoxidase (MPO) enzyme activity were analyzed. The results of the morphological, differentiation and immunophenotyping analyses confirmed that hypoxia preconditioned MSCs (HP-MSCs) conserve MSCs characteristics after preconditioning. However, HP-MSCs significantly expressed high mRNA level of hypoxia inducible factor 1-α and higher level of total protein. The findings of the current study showed that CM and HCM significantly reduced the amylase & lipase activity, the severity of pancreas tissue injury and the expression of IL-6 and MPO enzyme activity compared with the AP group. However, no significant difference between CM and HCM groups was demonstrated. Use of CM and HCM can attenuate cerulein-induced AP and decrease inflammation in the pancreas tissue in AP mice.
急性胰腺炎（AP）是一种以胰腺组织损伤和炎症为特征的炎症性疾病。利用间充质干细胞（MSCs）的旁分泌潜能为治疗炎症性疾病提供了一种有效的临床方法。我们研究了脂肪来源的MSC条件培养基（CM）和缺氧预处理的脂肪来源的MSC条件培养基（HCM）对小鼠雨蛙肽诱导的AP的治疗效果。通过腹腔注射雨蛙肽（75μg/kg/h×7次）在C57BL/6小鼠中诱导AP。在最后一次注射雨蛙肽1小时后，小鼠腹腔注射CM和HCM（500μL/小鼠/30分钟×3次）进行治疗。治疗12小时后，测量血清淀粉酶和脂肪酶水平。此外，分析胰腺病理变化、用于评估IL-6表达的免疫组织化学检查和胰腺髓过氧化物酶（MPO）酶活性。形态学、分化和免疫表型分析结果证实，缺氧预处理的MSCs（HP-MSCs）在预处理后保留了MSCs的特征。然而，HP-MSCs显著高表达缺氧诱导因子1-α的mRNA水平和更高水平的总蛋白。本研究结果表明，与AP组相比，CM和HCM显著降低了淀粉酶和脂肪酶活性、胰腺组织损伤的严重程度以及IL-6的表达和MPO酶活性。然而，CM组和HCM组之间未显示出显著差异。使用CM和HCM可以减轻雨蛙肽诱导的AP，并减少AP小鼠胰腺组织中的炎症。
