乌司他丁对心肺复苏后Wistar鼠大脑皮层炎症反应的影响  

The effects of Ulinastatin on the inflammatory response in cerebral cortex of Wistar rats after cardiopulmonary resuscitation

作　　者：崔喜梅[1] 熊海霞[2] 夏金明[1] 胡春林[1] 李欣[1] 禹移 荆小莉[3] 

机构地区：[1]中山大学附属第一医院急诊科,广州510080 [2]中山大学附属第三医院肾内科 [3]杭州师范大学附属医院急诊科

出　　处：《中华急诊医学杂志》2015年第1期33-37,共5页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金（81372022）;广东省科技计划项目（20128061700074）;2013中山大学国家级大学生创新实验项目

摘　　要：目的评价乌司他丁（UTI）对心肺复苏（CPR）后大鼠大脑皮层炎症因子TNF-α和IL-6表达及神经元细胞凋亡的影响。方法36只成年雄性Wistar大鼠采用交流电致颤的方式诱发室颤（VF），持续7min后进行CPR，建立VF／CPR模型。自主循环恢复（ROSC）后立即给予乌司他丁100000U／kg或等体积的PBS静脉注射。VF前和ROSC后2、4、8h采血检测血浆TNF-α、IL-6水平，并取大脑皮层进行定量PCR和Western blot检测TNF-α、IL-6mRNA表达和蛋白表达，检测核因子NF-κBp65的核浆转位情况。ROSC后72h行皮层NISSL和TUNEL染色计数顶叶皮层存活神经元细胞数和凋亡神经元细胞数。结果ROSC后UTI组2、4、8h血浆TNF-α质量浓度分别为（17．7±1．4）、（21．9±2．1）和（17．1±0．6），低于PBS组（t2h=1．42，t4h=2．93，t8h=4．22，各组P〈0．05）。UTI组2、4、8h血浆IL-6质量浓度（ng／mL）分别为（208．9±14．1）、（281．5±25．9）和（251．8±15．3），显著低于PBS组（t2h=3．87，t4h=2．45，t8h=3．74，各组P〈0．05）。ROSC后UTI组2、4、8h大脑皮层TNF-α、IL-6mRNA表达和蛋白表达量均显著低于PBS组。PBS组ROSC后2、4、8h大脑皮层NF-KBp65的核／浆转换率为（1．08±0．08）、（1．02±0．05）和（0．97±0．02），高于UTI组。ROSC后72hUTI组大脑皮层存活神经元细胞数为（22±3）个／400×400像素，多于PBS组的（19±2）个／400×400像素（Z=2．887，P=0．02）；凋亡细胞数UTI组为（10±2）个／400×400像素，低于PBS组的（13±3）个／400×400像素（Z=3．751P=0．01）。结论UTI降低ROSC后Wistar大鼠全身炎症反应，减少大脑皮层NF—κB通路的激活，减少致炎因子TNF-α和IL-6的表达，从而减少神经元细胞凋亡，促进细胞存活。Objective To evaluate the effects of Ulinastatin （UTI） on the expressions of TNF-α, IL- 6 and neurons apoptosis in cerebral cortex of rats after cardiopulmonary resuscitation （CPR）. Methods Thirty-six healthy male adult Wistar rats were induced ventrieular fibrillation untreated for 7 rain and then received CPR. The animals were infused UTI 100 000 U/kg or phosphate-bnffered solution （PBS） at once after ROSC. At 2, 4 and 8 h after ROSC, cerebral cortex were removed to determine the mRNA expressions and levels of TNF-α protein and IL-6 protein, the translocation ratio of NF-κB 1365 from cytoplasm to nucleus and the apoptotie neurons. Results The plasma levels of TNF-α （ng/mL） in animals of UTI group were （17.7 ±1.4）, （21.9 ±2. 1） and （17. 1 ±0.6） at 2, 4 and 8 h after ROSC respectively, and significantly lower than those in PBS group at the given intervals. Mean while, the levels of IL-6 （ng/mL） were （208.9 ± 14. 1 ）, （281.5 ± 25. 9） and （251.8 ± 15.3） at 2, 4 and 8 h after ROSC respectively in animals of UTI group, and lower than those in PBS group. The expressions of TNF-α mRNA and IL-6 mRNA and protein levels of TNF-α and IL-6 in UTI group were both lower than those in PBS group at given intervals, respectively. The transloeation ratio of NF-κB p65 from plasma to nucleus in PBS group at each given interval after ROSC was significantly higher than that in UTI group. The number of viable neurons in cerebral cortex in UTI group was higher than that in PBS group, while the number apoptosis neurons was fewer in UTI group. Conclusions UTI attenuated the general inflammatory response after ROSC in rat, decreased the activation of NF-KB pathway, and subsequently attenuated the expression of TNF-α and IL-6, and finally decreased the neurons apoptosis.

关 键 词：心肺复苏 乌司他丁 炎症反应 皮层 WISTAR大鼠 

分 类 号：R459.7[医药卫生—急诊医学]