Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China.
J Transl Med. 2012 Dec 7;10:244. doi: 10.1186/1479-5876-10-244.
We tested whether apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) were superior to healthy (H)-ADMSCs at attenuating organ damage and mortality in sepsis syndrome following cecal ligation and puncture (CLP).
Adult male rats were categorized into group 1 (sham control), group 2 (CLP), group 3 [CLP + H-ADMSC administered 0.5, 6, and 18 h after CLP], group 4 [CLP + A-ADMSC administered as per group 3].
Circulating peak TNF-α level, at 6 h, was highest in groups 2 and 3, and higher in group 4 than group 1 (p < 0.0001). Immune reactivity (indicated by circulating and splenic helper-, cytoxic-, and regulatory-T cells) at 24 and 72 h exhibited the same pattern as TNF-α amongst the groups (all p < 0.0001). The mononuclear-cell early and late apoptosis level and organ damage parameters of liver (AST, ALT), kidney (creatinine) and lung (arterial oxygen saturation) also displayed a similar pattern to TNF-α levels (all p < 0.001). Protein levels of inflammatory (TNF-α, MMP-9, NF-κB, ICAM-1), oxidative (oxidized protein) and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than group 1, whereas anti-apoptotic (Bcl-2) biomarker was lower in groups 2 and 3 than in group 1 but anti-oxidant (GR, GPx, HO-1, NQO-1) showed an opposite way of Bcl-2; these patterns were reversed for group 4 (all p < 0.001). Mortality was highest in group 3 and higher in group 2 than group 4 than group 1 (all p < 0.001).
A-ADMSC therapy protected major organs from damage and improved prognosis in rats with sepsis syndrome.
我们测试了凋亡脂肪间充质干细胞（A-ADMSCs）是否优于健康脂肪间充质干细胞（H-ADMSCs），以减轻盲肠结扎和穿刺（CLP）后脓毒症综合征中的器官损伤和死亡率。
成年雄性大鼠分为 1 组（假对照）、2 组（CLP）、3 组（CLP 后 0.5、6 和 18 小时给予 H-ADMSC）、4 组（按 3 组给予 A-ADMSC）。
循环中 TNF-α 水平的峰值在 6 小时时在 2 组和 3 组中最高，在 4 组中高于 1 组（p<0.0001）。24 和 72 小时的循环和脾辅助性、细胞毒性和调节性 T 细胞的免疫反应表现出与 TNF-α 相同的模式（均 p<0.0001）。单核细胞早期和晚期凋亡水平以及肝（AST、ALT）、肾（肌酐）和肺（动脉血氧饱和度）的器官损伤参数也表现出与 TNF-α 水平相似的模式（均 p<0.001）。炎症（TNF-α、MMP-9、NF-κB、ICAM-1）、氧化（氧化蛋白）和凋亡（Bax、caspase-3、PARP）生物标志物的蛋白水平在 2 组和 3 组中高于 1 组，而抗凋亡（Bcl-2）生物标志物在 2 组和 3 组中低于 1 组，但抗氧化（GR、GPx、HO-1、NQO-1）则与 Bcl-2 相反；这些模式在 4 组中均发生逆转（均 p<0.001）。3 组的死亡率最高，2 组高于 4 组，4 组高于 1 组（均 p<0.001）。
A-ADMSC 治疗可保护脓毒症综合征大鼠的主要器官免受损伤，并改善其预后。
