Bankey P, Beecherl E, Bibus D, See D, McIntyre K
Department of Surgery, University of Texas Southwestern Medical Center at Dallas, USA.
Arch Surg. 1995 Dec;130(12):1266-72. doi: 10.1001/archsurg.1995.01430120020003.
To test the hypothesis that pretreatment with liposomes enriched with the omega 3 fatty acid docosahexaenoic acid (22:6 omega 3) will alter the Kupffer's cell and systemic cytokine (tumor necrosis factor and interleukin-6) response to endotoxin challenge, and to demonstrate alterations in Kupffer's cell phospholipid fatty acid composition after in vivo liposome treatment.
Nonrandomized controlled laboratory investigation in Wistar rats.
Animals were assigned to three pretreatment groups: no liposomes; liposomes, 100 mg/kg; or liposomes, 400 mg/kg given by bolus intravenous injection with the animals under inhalation anesthesia. Eighteen hours after liposome treatment, each group was challenged with Escherichia coli lipopolysaccharide (3 mg/kg intraperitoneally in 10 mL of lactated Ringer's solution) or lactated Ringer's solution only. In a separate set of experiments, Kupffer's cells were obtained from animals pretreated with liposome, 400 mg/kg, or controls and challenged with lipopolysaccharide (1, 100, or 10(4) ng/mL) in vitro.
Serum and Kupffer's cell supernatant tumor necrosis factor and interleukin-6 bioactivity, Kupffer's cell phospholipid fatty acid composition, survival, and liver histologic findings.
In vivo liposome pretreatment (400 mg/kg) resulted in significant increases in serum tumor necrosis factor and interleukin-6 levels 90 minutes after intraperitoneal lipopolysaccharide challenge (P < .05 vs no liposomes). Kupffer's cells isolated from liposome-treated animals (400 mg/kg) compared with untreated controls release significantly more tumor necrosis factor and interleukin-6 after lipopolysaccharide stimulation in vitro in a dose-dependent response (P < .05). Liposome treatment increased total polyunsaturated fatty acid, total omega 3, and docosahexaenoic acid 22:6 omega 3 content in Kupffer's cell phospholipids compared with untreated controls. Survival 24 hours after lipopolysaccharide challenge was reduced by liposome (400 mg/kg) pretreatment (P < .05 by chi 2 test). Livers from each treatment group demonstrated focal areas of hepatocyte necrosis and inflammatory cells.
Liposome pretreatment increases the circulating and Kupffer's cell cytokine response to endotoxemia, increases Kupffer's cell polyunsaturated fatty acid content, and is associated with reduced survival.
验证富含ω-3脂肪酸二十二碳六烯酸（22:6ω-3）的脂质体预处理是否会改变库普弗细胞和全身细胞因子（肿瘤坏死因子和白细胞介素-6）对内毒素攻击的反应，并证明体内脂质体处理后库普弗细胞磷脂脂肪酸组成的变化。
对Wistar大鼠进行非随机对照实验室研究。
将动物分为三个预处理组：不使用脂质体；脂质体，100mg/kg；或脂质体，400mg/kg，在吸入麻醉下通过静脉推注给药。脂质体处理18小时后，每组用大肠杆菌脂多糖（3mg/kg腹腔内注射于10mL乳酸林格氏液中）或仅用乳酸林格氏液进行攻击。在另一组实验中，从用400mg/kg脂质体预处理的动物或对照组中获取库普弗细胞，并在体外用脂多糖（1、100或10⁴ng/mL）进行攻击。
血清和库普弗细胞上清液中肿瘤坏死因子和白细胞介素-6的生物活性、库普弗细胞磷脂脂肪酸组成、存活率和肝脏组织学结果。
体内脂质体预处理（400mg/kg）导致腹腔内注射脂多糖90分钟后血清肿瘤坏死因子和白细胞介素-6水平显著升高（与不使用脂质体相比，P<.05）。与未处理的对照组相比，从脂质体处理的动物（400mg/kg）分离的库普弗细胞在体外脂多糖刺激后释放的肿瘤坏死因子和白细胞介素-6明显更多，呈剂量依赖性反应（P<.05）。与未处理的对照组相比，脂质体处理增加了库普弗细胞磷脂中总多不饱和脂肪酸、总ω-3和二十二碳六烯酸22:6ω-3的含量。脂多糖攻击24小时后的存活率因脂质体（400mg/kg）预处理而降低（χ²检验，P<.05）。每个治疗组的肝脏均显示肝细胞坏死和炎性细胞的局灶性区域。
脂质体预处理增加了对内毒素血症的循环和库普弗细胞细胞因子反应，增加了库普弗细胞多不饱和脂肪酸含量，并与存活率降低有关。
