Bluth Martin H, Kandil Emad, Mueller Catherine M, Shah Vishal, Lin Yin-Yao, Zhang Hong, Dresner Lisa, Lempert Leonid, Nowakowski Maja, Gross Richard, Schulze Robert, Zenilman Michael E
SUNY Downstate Medical Center, Department of Surgery, Brooklyn, NY 11203, USA.
Crit Care Med. 2006 Jan;34(1):188-95. doi: 10.1097/01.ccm.0000196212.56885.50.
Sophorolipids, a family of natural and easily chemoenzymatically modified microbial glycolipids, are promising modulators of the immune response. The potential of the therapeutic effect of sophorolipids was investigated in vivo in a rat model of sepsis and in vitro by analysis of nitric oxide and cytokine production.
Prospective, randomized animal study.
Experimental laboratory.
Male Sprague-Dawley rats, 200-240 g.
Intra-abdominal sepsis was induced in vivo in 166 rats via cecal ligation and puncture (CLP); 60 rats were used to characterize the model. The remaining rats were treated with sophorolipids or vehicle (dimethylsulfoxide [DMSO]/physiologic saline) by intravenous (iv) tail vein or intraperitoneal (IP) injection immediately post-CLP (25/group). Survival rates were compared at 36 hrs after surgery. In vitro, macrophages were cultured in lipopolysaccharide (LPS) +/- sophorolipid and assayed for nitric oxide (NO) production and gene expression profiles of inflammatory cytokines. In addition, splenic lymphocytes isolated from CLP rats +/- sophorolipid treatment (three per group) were analyzed for cytokine production by RNase protection assay.
CLP with 16-gauge needles optimized sepsis induction and resultant mortality. Sophorolipid treatment improved rat survival by 34% (iv) and 14% (IP) in comparison with vehicle controls (p < .05 for iv treatment). Sophorolipids decreased LPS-induced macrophage NO production by 28% (p < .05). mRNA expression of interleukin (IL)-1beta was downregulated by 42.5 +/- 4.7% (p < .05) and transforming growth factor (TGF)-beta1 was upregulated by 11.7 +/- 1.5% (p < .05) in splenocytes obtained 6 hrs postsophorolipid treatment. LPS-treated macrophages cultured 36 hrs with sophorolipids showed increases in mRNA expression of IL-1alpha (51.7%), IL-1beta (31.3%), and IL-6 (66.8%) (p < .05).
Administration of sophorolipids after induction of intra-abdominal sepsis significantly decreases mortality in this model. This may be mediated in part by decreased macrophage NO production and modulation of inflammatory responses.
槐糖脂是一类天然且易于通过化学酶法修饰的微生物糖脂，是很有前景的免疫反应调节剂。通过在脓毒症大鼠模型中进行体内研究以及分析一氧化氮和细胞因子的产生来体外研究槐糖脂的治疗效果潜力。
前瞻性、随机动物研究。
实验实验室。
体重200 - 240克的雄性斯普拉格 - 道利大鼠。
通过盲肠结扎和穿刺（CLP）在166只大鼠体内诱导腹腔脓毒症；60只大鼠用于模型特征描述。其余大鼠在CLP后立即通过静脉（iv）尾静脉或腹腔（IP）注射用槐糖脂或赋形剂（二甲基亚砜[DMSO]/生理盐水）进行治疗（每组25只）。比较术后36小时的存活率。在体外，将巨噬细胞培养于脂多糖（LPS）±槐糖脂中，并检测一氧化氮（NO）的产生以及炎性细胞因子的基因表达谱。此外，通过核糖核酸酶保护试验分析从CLP大鼠±槐糖脂治疗组（每组3只）分离的脾淋巴细胞的细胞因子产生情况。
用16号针头进行CLP可优化脓毒症诱导及由此产生的死亡率。与赋形剂对照组相比，槐糖脂治疗使大鼠存活率提高了34%（静脉注射）和14%（腹腔注射）（静脉注射治疗p < 0.05）。槐糖脂使LPS诱导的巨噬细胞NO产生减少了28%（p < 0.05）。在槐糖脂治疗6小时后获得的脾细胞中，白细胞介素（IL）-1β的mRNA表达下调了42.5±4.7%（p < 0.05），转化生长因子（TGF）-β1的mRNA表达上调了11.7±1.5%（p < 0.05）。用槐糖脂培养36小时的LPS处理的巨噬细胞显示IL-1α（51.7%）、IL-1β（31.3%）和IL-6（66.8%）的mRNA表达增加（p < 0.05）。
腹腔脓毒症诱导后给予槐糖脂可显著降低该模型中的死亡率。这可能部分是通过减少巨噬细胞NO产生和调节炎症反应来介导的。
