摘要目的 研究不同剂量盐酸戊乙奎醚(penehycliline hydrxhloride,PHC)对创伤性休克兔肠黏膜损伤的保护作用.方法采用Lamson's法建立创伤性休克动物模型,30只健康日本长耳大白兔,采用随机数字表分为5组(每组6只):对照组(Con组),0.9％氯化钠溶液复苏组(NS组),低剂量组(PHCL组)(0.05 mg/kg)、中剂量组(PHCM组)(0.15 mg/kg)和高剂量组(PHCH组)(0.45 mg/kg).分别在休克前(T1),休克末(T2),复苏后即刻(T3)、2(T4)、4(T5)、6 h(T6)等6个时间点监测平均动脉压(MAP)和心率(HR)并采血检测二胺氧化酶(diamine oxidase,DAO)活性和D-乳酸浓度.实验结束后放血处死动物取小肠组织,光镜下检查病理学变化.结果 各实验组动物T2点的MAP显著降低(均≤45 mm Hg)(1mm Hg=0.133 kPa); T3-6点NS组的MAP分别是(68.8±3.0)、(67.5±5.3)、(71.0±3.7)、(71.0±2.4)mm Hg,显著低于休克前(94.3±1.7)mm Hg、Con组(82.8±4.1)、(89.8±6.6)、(82.4±3.3)、(94.4±6.2)mm Hg和PHCM组(83.2±13.6)、(82.2±9.0)、(83.8±8.9)、(85.4±8.1) mm Hg,差异有统计学意义(P＜0.05或P＜0.01).T3-6点NS组的HR( 185±11)、(181±7)、(164±13)、(164±13)次/min较休克前(276±13)次/min显著降低,与Con组和PHCM组比较差异有统计学意义(P＜0.05或P＜0.01).T2-6点各实验组动物的血浆DAO活性和D-乳酸浓度较休克前显著升高；T3-6点NS组的血浆DAO活性(0.393±0.020)、(0.586±0.017)、(0.844±0.036)、(0.568±0.016) μ/ml和D-乳酸浓度(8.2920.364)、(7.539±0.098)、(5.991±0.180)、(7.108±0.372) mmol/L显著高于PHCL组和PHCH组,后两组又显著高于PHCM组(0.111±0.016)、(0.302±0.020)、(0.501±0.014)、(0.183±0.018) μ/ml,(5.664±0.546)、( 4.609±0.292)、(3.310±0.363)、(4.720-0.205) mmol/L,差异有统计学意义(P＜0.05或P＜0.01).病理组织学检查显示PHCM的组肠黏膜损伤程度轻于其他试验组.结论 PHC联合0.9％氯化钠溶液复苏能稳定创伤性休克兔的血流动力学；对创伤性休克造成的肠黏膜损伤有确切的保护作用,中剂量的PHC保护效果更为显著；血浆DAO活性、D-乳酸浓度可以评估肠黏膜损伤及屏障功能情况.

abstractsObjective To investigate the protective effects of penehyclidine hydrochloride(PHC) on intestinal mucosa injury in rabbits with traumatic shock. Methods The animal model of traumatic shock was established according to Lamson's method.Thirty rabbits were divided into five groups randomly:control group (Con group),traumatic shock group resuscitation with normal saline (NS group),traumatic shock group resuscitation with pcnehyclidine hydrochloride in low dosages (0.05 mg/kg,PHCL group),middle dosages group (0.15 mg/kg,PHCM group) and high dosages group (0.45 mg/kg,PHCH group).At pre-shock,postshock,four time points (T3-T(o)) after resuscitation,mean arterial blood pressure(MAP) and heart rate(HR) were monitored.Plasma diamine oxidase (DAO) activity and lactic acid concentration were measured by spectrophotometry at defined time points.At the end of experiment,the animals were sacrificed and the samples were collected.The pathological changes of the samples were observed under microscope. Results There were no significant differences in MAP before shock among the five groups.MAP in NS group,PHCL group,PHCM group and PHCH group decreased post-shock,but there were no significant differences in MAP among groups.At T3-T6 time points,MAP in NS group (68.8±3.0),(67.5±5.3),(71.0±3.7),(71.0±2.4) mm Hg( 1 mm Hg=0.133 kPa),respectively was significantly lower than that before shock (94.3±1.7) mm Hg,also lower than that in the Con group (82.8±4.1),(89.8±6.6),(82A±3.3),(94.4±6.2) mm Hg,respectively and the PHCM gronp (83.2±13.6),(82.2±9.0),(83.8±8.9),(85.4±8.1) mm Hg,respectively.There were no significant differences in HR pre-shock and post-shock among the five groups.At T3-T6 time points,HR in the NS group (185±11),(181±7),(164±13),(164±13) hpm,respectively were signifieandy lower than that at T1(276±13) bpm,also significantly (P＜0.05 or P＜0.01 ) lower than that in the Con group and the PHCM group.The plasma DAO activity and D-lactate concentration in the Ns group,PHCL group,PHCM group,PHCH group were significantly increased at T2-T6 time points.Furthermore,at T3-T6 time poinls,the plasma DAO activity (0,393±0,020),(0.586±0.017),(0.844±0.036),(0.568±0.016) μ/ml,respectively and D-lactate concentration(8.292±0.364),(7.539±0.098),(5.991±0.180),(7,108±0.372) mmol/L,respectively in the NS group were significantly higher than that in the PHCL group and PHCH group; the plasma DAO activity and D-lactate concentration in the PHCL group and PHCH group were significantly higher than in the PHCM group (0.111±0.016),(0.302±0.020),(0.501±0.014),(0.183±0.018)μ/ml; (5.664±0.546),(4.609±0.292),(3.310±0,3634),(4.720±0.205)mmol/L(P＜O.05orP＜0.0l).Intestinal mucosal injury in the PHCM group was significantly reduced compared with tbat in the NS group.Conclusions The resuscitation of PHC combinition with Mnormal saline can stabilize hemodynamics in rabbits with traumatic shock.There was a significant protective effect on intestinal mucosal injury induced by traumatic shock,especially in the PHCM group.The plasma DAO activity and D-lactate concentration can be used to assess the extent of intestinal mucosa injury and barrier function.