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目的探讨大鼠内毒素休克模型的肠道病变、血液TNF-α、IL-1β、IL-10改变和血管活性肠肽(VIP)的保护作用。方法28只成年SD大鼠随机分成3组:对照组(8只),内毒素休克组(10只)和血管活性肠肽干预组(10只)。内毒素休克组大鼠左侧颈外静脉注射内毒素10 mg/kg,血管活性肠肽干预组注射同量内毒素后,即刻注射血管活性肠肽5 nmol,对照组注射等容量生理盐水。各组于实验开始后1、2、4、6 h分别留取血液,用ELISA法测定TNF-α、IL-1β和IL-10水平。大鼠自然死亡和实验持续6 h时放血处死,留取小肠段,进行病理学检查。结果内毒素休克组和血管活性肠肽干预组血液TNFα-、IL-1β和IL-10水平与对照组相比呈现升高(P<0.05 orP<0.01),其中TNF-α于2 h时达到高峰点,IL-1β和IL-10持续升高至6 h时间点。血管活性肠肽干预组TNF-α和IL-1β升高幅度低于内毒素休克组,IL-10升高幅度高于内毒素休克组(P<0.01)。注射内毒素后小肠光镜和电镜下均显示肠段病变,内毒素休克组病变明显较血管活性肠肽干预组严重。结论血管活性肠肽可减轻内毒素休克大鼠肠道病变,其保护机制与下调促炎症细胞因子和上调抑炎症细胞因子的表达有关。血管活性肠肽是脓毒症休克治疗中有潜力的免疫调节物质。
Objective To investigate the protective effects of intestinal tract injury, changes of blood TNF-α, IL-1β, IL-10 and vasoactive intestinal peptide (VIP) in rats with endotoxic shock. Methods Twenty-eight adult SD rats were randomly divided into three groups: control group (n = 8), endotoxic shock group (n = 10) and vasoactive intestinal peptide intervention group (n = 10). In the endotoxin shock group, the left external jugular vein was injected with endotoxin 10 mg / kg. After the same amount of endotoxin was injected into the vasoactive intestinal peptide group, 5 nmol of vasoactive intestinal peptide was injected immediately and the control group was injected with the same volume of normal saline. The blood samples were collected at 1, 2, 4 and 6 h after the start of the experiment, and the levels of TNF-α, IL-1β and IL-10 were measured by ELISA. Rats were sacrificed and the animals were sacrificed at 6 hours after their death and the small intestine was taken for pathological examination. Results Compared with the control group, the levels of TNFα-, IL-1β and IL-10 in the endotoxin shock group and the vasoactive intestinal peptide group were significantly increased (P <0.05 or P <0.01), and the level of TNF-α reached at 2 h Peak point, IL-1β and IL-10 continued to rise to 6 h time point. The increase of TNF-α and IL-1βin vasoactive intestinal peptide intervention group was lower than that of endotoxin shock group, and the increase of IL-10 was higher than that of endotoxin shock group (P <0.01). Small intestine injection of endotoxin light microscopy and electron microscopy showed bowel lesions, endotoxic shock group was significantly more than vasoactive intestinal peptide intervention group. Conclusion Vasoactive intestinal peptide can relieve intestinal pathological changes induced by endotoxic shock in rats. The protective mechanism is related to the downregulation of proinflammatory cytokines and the upregulation of anti - inflammatory cytokines. Vasoactive intestinal peptide is a potential immunomodulatory substance in the treatment of septic shock.