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摘要：
目的 观察并探讨下胸段硬膜外阻滞对失血性休克复苏大鼠肠上皮屏障（intestinal epithelial barrier, IEB）及肠胶质细胞（enteric glial cell, EGC）活化的影响。 方法 选用经Bahar改良法行下胸段硬膜外置管成功的SD大鼠72只，按随机数字表法分为4组，每组18只：假手术组（S组）、休克复苏组（C组）、休克复苏+硬膜外注射生理盐水组（N组）、休克复苏+硬膜外注射罗哌卡因组（T组）。S组仅进行动静脉置管，其余3组均采用Wiggers改良法制备压力控制型失血性休克及生理盐水复苏模型。T组于放血前30 min经硬膜外导管注射0.075%罗哌卡因100 μl/kg，N组以等量生理盐水替代。观察各组大鼠复苏后72 h生存率，记录动静脉置管成功后（T0）、硬膜外注射后30 min（T1）、休克30 min（T2）、休克60 min（T3）、复苏30 min（T4）、复苏60 min（T5）时大鼠的MAP和HR，并于T0、T3和T5行动脉血气分析检测pH、乳酸水平及Hct；复苏后3 h取门静脉血和回肠标本，检测门静脉内毒素脂多糖（lipopolysaccharide, LPS）水平，计算肠湿/干比（wet/dry ratio, W/D），Chiu氏评分法评估肠黏膜病理学改变，Western blot检测肠黏膜紧密连接蛋白Occludin及EGC标记蛋白肠胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）的表达。 结果 与C组和N组比较，T组大鼠生存率及中位生存时间改善，T4和T5时间点MAP及HR降低，T3和T5时间点pH和乳酸水平改善，W/D、LPS水平和Chiu氏评分降低，肠GFAP和Occludin表达增高，差异均有统计学意义（P<0.05）。 结论 下胸段硬膜外阻滞能够保护失血性休克复苏大鼠IEB的结构与功能，改善内环境并提高生存率，其机制与活化肠EGC有关。
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Abstract: Ｏｂｊｅｃｔｉｖｅ To investigate the effects of lower thoracic epidural blockade on integrity of intestinal epithelial barrier(IEB) and activation of enteric glial cell(EGC) in rats with hemorrhagic shock and resuscitation. Methods Seventy-two SD rats with epidural catheterization according to a modified method described by Bahar et al. were randomly divided into four groups with 18 in each group: sham group(group S), control group(group C), normal saline group(group N) and thoracic epidural blockade group(group T). In group S, rats were just received vascular cannulation, whereas the rats in other groups were subjected to hemorrhagic shock and resuscitation with normal saline according to the modified method described by Wiggers. Thirty minutes before bleeding, either 0.075% ropivacaine(group T) or normal saline(group N) 100 μl/kg was infused through thoracic epidural catheters. The survival rates of rats in 72 h after resuscitation were evaluated. The MAP and HR were monitored after vascular cannulation(T0), 30 min after epidural infusion(T1), 30 min of shock(T2), 60 min of shock(T3), 30 min and 60 min after resuscitation(T4 and T5 respectively). Arterial blood samples were collected for blood gas analysis at T0, T3 and T5. At 3 h following resuscitation, the severity of intestinal edema, the pathological changes of intestinal mucosa, and the function of IEB were evaluated by wet/dry ratio(W/D), Chiu＇s score, and lipopolysaccharide(LPS) concentrations in the portal vein, respectively. The expression of Occludin and glial fibrillary acidic protein(GFAP), a marker of EGCs, were determined by western blot. Results Compared with group C and group N, the survival rates and median survival time of group T were significantly promoted (P<0.05), While MAP and HR decreased at T4 and T5, the levels of pH and lactic acid at T3 and T5 were alleviated (P<0.05). Besides these, in group T, the levels of W/D, Chiu＇s score and LPS were decreased while the expression of Occludin and GFAP were increased significantly in comparison with group C and group N(P<0.05). Conclusions Lower thoracic epidural blockade attenuates IEB impairment induced by hemorrhagic shock and resuscitation in rats, alleviating internal environment disturbance and thus promoting survival rates after resuscitation, whose mechanism is related to activation of EGC.
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