Department of Pharmacology and Toxicology, Faculty of Pharmacy, MTI University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Inflammation. 2018 Mar;41(2):541-554. doi: 10.1007/s10753-017-0710-6.
Sepsis is a systemic inflammatory disorder which often occurs during extremely stressful conditions such as trauma, burn, shock, and infection. This study investigated the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) against hepatic, renal, and pulmonary responses caused by a single administration of lipopolysaccharide (LPS) (10 mg/kg, i.p) in rats. Treatment with BM-MSCs (5 × 10 in 0.1 ml PBS, i.p.) 3 h after LPS antagonized the LPS-induced increment of the liver enzymes (ALT, AST) and kidney functions (BUN, sCr). BM-MSCs decreased tissue levels of P38-MAPK, NF-κB, STAT-3, TNF-α, IL-1β, iNOS, Bax together with elevation of the anti-inflammatory cytokine IL-10 and the anti-apoptotic biomarker Bcl-2. Meanwhile, rats exhibited marked reduction of the broncho-alveolar lavage fluid levels of TNF-α, IL-1β, and IFN-γ. Interestingly, BM-MSCs normalized both broncho-alveolar lavage fluid (BALF) neutrophils count and lung wet/dry ratios. Briefly, these findings may provide a preclinical platform for the management of LPS-induced sepsis using BM-MSCs via their ameliorative anti-inflammatory, anti-oxidant, and anti-apoptotic potentials.
脓毒症是一种全身性炎症失调，常发生在创伤、烧伤、休克和感染等极度应激状态下。本研究探讨了骨髓间充质干细胞（BM-MSCs）对单次腹腔注射脂多糖（LPS）（10mg/kg）引起的肝、肾和肺反应的治疗效果。在 LPS 后 3 小时用 BM-MSCs（5×10 在 0.1ml PBS 中，腹腔内注射）治疗可拮抗 LPS 诱导的肝酶（ALT、AST）和肾功能（BUN、sCr）升高。BM-MSCs 降低了 P38-MAPK、NF-κB、STAT-3、TNF-α、IL-1β、iNOS、Bax 的组织水平，同时升高了抗炎细胞因子 IL-10 和抗凋亡生物标志物 Bcl-2。同时，大鼠支气管肺泡灌洗液中 TNF-α、IL-1β 和 IFN-γ 的水平明显降低。有趣的是，BM-MSCs 使支气管肺泡灌洗液（BALF）中性粒细胞计数和肺湿/干比正常化。总之，这些发现可能为使用 BM-MSCs 通过其改善的抗炎、抗氧化和抗凋亡潜力来管理 LPS 诱导的脓毒症提供一个临床前平台。
