血必净对高原MODS模型的防治作用研究及与炎性因子表达的关系

发布时间：2019-01-07 07:36

【摘要】：目的：本研究采用长白猪多器官功能障碍综合征（MODS）模型，通过实验研究，探讨中药血必净防治高原多器官功能障碍综合征（H-MODS）的疗效及其机制，为临床应用提供实验依据。方法：选用体质量为10～15kg的2月龄健康雄性长白猪24只，于兰州（海拔1520m）适应性喂养1周后，急进至桑科草原（海拔3200m）行动物实验。所有长白猪麻醉后，随机分为空白对照组（A组）、模型组（B组）、血必净低剂量组（C组）、血必净高剂量组（D组），每组6只。B组、C组、D组分别经耳缘静脉滴注内毒素（LPS），总量0.35mg/kg，制作MODS模型。内毒素输毕后，C组给予：血必净注射液1.5mL/kg，2/日；D组给予：血必净注射液3mL/kg，2/日； A、B组给予等体积生理盐水，2/日；共治疗3天。于不同时间段观察各组长白猪的生命体征、脏器功能指标（丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、肌酐（CR））、炎性因子（TNF-α、IL-1）及脏器病理改变，对比各组的统计学差异及组内各时间段的变化规律，，得出结论。实验数据应用SPSS17.0统计分析软件包进行分析。结果：1. B、C、D组体温、呼吸、心率明显升高，与A组相比，差异有统计学意义（P0.05或P0.01）；B组呼吸、心率较C、D组升高，差异有统计学意义（P0.05,P0.05）；24h B组死亡率为33.3%，C、D组死亡率均为16.6%。2. B、C、D组血白细胞（WBC）呈“勺型”变化。B组变化幅度较C、D组明显（P0.05或P0.01）。48h时，D组WBC升高幅度较C组低（P0.05）。3. B、C、D组AST、ALT、TBIL、CR于6h均较A组明显上升，差异有统计学意义（P0.05或P0.01），至48h达到峰值，以B组升高最明显，与C、D组比较，差异有统计学意义（P0.05或P0.01），后逐渐下降；24h后，D组AST、CR升高幅度较C组低（P0.05, P0.05）。4.与A组相比，B、C、D组TNF-α、IL-1表达于6h明显升高（均为P0.01），12h达到峰值（均为P0.01），以B组上升趋势最明显，与C、D组相比，差异有统计学意义（P0.05或P0.01），后逐渐下降。D组24h TNF-α及48h IL-1表达均低于C组，差异显著（P0.05, P0.05）；24h B、C、D组NF-κBmRNA表达量明显高于A组，差异有统计学意义（均为P0.01），以B组升高幅度最大；72h时，B组NF-κBmRNA表达量仍高于A组（P0.05），而C、D组表达量已接近A组水平。结论：血必净注射液干预治疗内毒素诱导的高原长白猪MODS模型，不仅可降低其死亡率，减轻内毒素所致的肝、肾功能损伤，而且可以阻断炎性介质的释放，降低炎性因子对机体产生的刺激作用，提高H-MODS的生存率，表明血必净对H-MODS有良好的防治作用。
[Abstract]:Objective: to investigate the effect and mechanism of Xuebijing, a Chinese medicine, on preventing and treating multiple organ dysfunction syndrome (H-MODS) at high altitude by using (MODS) model of Landrace pig multiple organ dysfunction syndrome. To provide experimental basis for clinical application. Methods: 24 healthy 2-month-old male Landrace pigs with body mass of 10~15kg were fed adaptively in Lanzhou (1520m above sea level) for one week, and then the animal experiment was carried out in the mulberry steppe (3200m above sea level). After anesthesia, all Landrace pigs were randomly divided into control group (group A), model group (group B), low dose group of Xuebijing (group C) and high dose group of Xuebijing (group D). Group D was given endotoxin (LPS), 0.35 mg / kg via ear vein to make MODS model. After endotoxin infusion, group C was given Xuebijing injection 1.5 mL / kg / d, group D was given 3 mL 路kg -1 路kg -1 / d of Xuebijing injection, and group A B was given saline of the same volume, 2 days, for 3 days. The vital signs and organ function indexes (alanine aminotransferase (ALT),) aspartate aminotransferase (AST),) total bilirubin (TBIL), creatinine (CR), inflammatory factor (TNF- 伪) were observed in different periods of time. IL-1) and pathological changes of viscera. The experimental data were analyzed by SPSS17.0 statistical analysis software package. Results: 1. The body temperature, respiration and heart rate in group D were significantly higher than those in group A (P0.05 or P0.01); B, P 0.05). The mortality rate of group B was 33.3% and that of group D was 16.60.2. The change of leukocyte (WBC) in group B was significantly higher than that in group C (P0.05 or P0.01). At 48 h, the increase of WBC in group D was lower than that in group C (P0.05). The AST,ALT,TBIL,CR in group B was significantly higher than that in group A at 6 h (P0.05 or P0.01), and reached its peak value at 48 h, especially in group B, which was significantly higher than that in group C (P 0.05 or P0.01), and was significantly higher than that in group C (P < 0.05). The difference was statistically significant (P0.05 or P0.01), and then decreased gradually. After 24 hours, the increase of AST,CR in group D was lower than that in group C (P 0.05, P 0.05). Compared with group A, the expression of TNF- 伪 and IL-1 in group B was significantly higher than that in group A at 6 h (all P0.01), and reached a peak at 12 h (P0.01). The expression of TNF- 伪 and IL-1 at 24 h and 48 h in group D were lower than those in group C (P0.05 or P0.01), and the difference was significant (P0.05, P0.05). The expression of NF- 魏 BmRNA in group B was significantly higher than that in group A (P0.01). At 72 h, the expression of NF- 魏 BmRNA in group B was still higher than that in group A (P0.05), while the expression of NF- 魏 BmRNA in group C was close to the level of group A. Conclusion: the intervention of Xuebijing injection in the treatment of MODS model induced by endotoxin can not only reduce the mortality, alleviate the damage of liver and kidney function induced by endotoxin, but also block the release of inflammatory mediators. Reducing the stimulating effect of inflammatory factors on the body and increasing the survival rate of H-MODS showed that Xuebijing had a good preventive and therapeutic effect on H-MODS.
【学位授予单位】：甘肃中医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R259;R285.5

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