摘要
目的探讨低分子肝素对脓毒症大鼠肺组织高迁移率族蛋白B1（HMGB-1）的影响以及对由大鼠盲肠结扎穿孔（CLP）所致的急性肺损伤的保护作用。方法144只SPF级雄性sD大鼠（体质量200～220g）被随机分为假手术组（48只）、盲肠结扎穿孔术（CLP）后常规治疗组（48只）及常规加低分子肝素治疗组（48只），分别施以假手术（A组）或CLP（B组和C组）。术后各组立即腹腔注射生理盐水（NS）2mL及头孢曲松（30mg／kg）、C组加用低分子肝素10U（50U／kg）。以术后3、6、12、18、24、48h为观察点，观察各组大鼠术后活动、进食、竖毛、腹泻、眼球凹陷、呼吸等情况；活杀并行脓毒症大鼠评分及观察死亡率、肺湿干质量比（W／D）及病理学变化。采用逆转录-聚合酶链反应（RT—PCR）技术测肺组织HMGB-1mRNA的表达；采用Westernblot法检测肺组织HMGB-1蛋白的表达。结果注射低分子肝素（达肝素钠）（50U／kg）的脓毒症大鼠死亡率及肺部高迁移率族蛋白-1的蛋白表达及其mRNA的表达与对照组比较均明显降低（P〈0．05），低分子肝素干预组中脓毒症大鼠评分及肺湿干比、病理损害均减少。结论低分子肝素能够抑制CLP引起的脓毒症过程中的晚期炎症介质释放，改善CLP模型（严重腹腔感染）引起的急性肺损伤过程中的肺干湿质量比、病理改变及死亡率。本实验推测这种作用是通过低分子肝素对炎症引起的肺损伤中凝血一炎症轴的影响而实现的。
Objective To observe the influence of low molecular weight heparin on systemic inflammation, including high mobility group box 1 protern （ HMGB - 1 ）and protective effect on acute lung injuty induced by cecal ligation and puncture（CLP）. Discuss the mechanism of this effect. Methods A sepsis model reproduced by CLP, and 144 male SD rats were randomly divided into normal control （A）, CLP group （ B）, the LMWH treatment group （ C ）, n = 48. Inject saline and ceftriaxone （ B, C ） or LMWH（C） once after operation. Observe points were made at 3,6, 12, 18,24,48 h, the rats were anesthesized and killed, mortality, lungs wet/dry ratio and Pathology change were determined. HMGB - 1 mRNA and protein of lung tissues were calculated by RT - PCR and Western blot. TNF -α and IL - 6 of blood plasma calculated by ELISA. Results There was significantly in each index between CLP group and control group（ P 〈 0. 05 ）. Compared with CLP group, there was a markly decrease in lung wet/dry ratio, the mortality and HMGB - 1 mRNA and ptotein expression on lung tissues （ P 〈 0.05 ）. The lung injury has decresed in LMWH group compared with CLP group. Conclusion LMWH can decreases cytokin-e and HMGB -1 levels during CLP -induced inflammation. As a result, LMWH ameli - orated lungpathology and reduces mortality in CLP - induced systemicinflammation in a rat model. This effect may be mediated through the inhibition of axis of inflammation and coagulation.
出处
《中国急救医学》
CAS
CSCD
北大核心
2010年第8期720-724,I0001,共6页
Chinese Journal of Critical Care Medicine
基金
上海市重点学科建设基金（No.08GW2X1103）
