卡巴胆碱对烧创伤后肠道功能障碍影响的研究

目的观察肠道内给予卡巴胆碱对兔肠部分缺血再灌注(I/R)损伤及重度烧伤患者肠道功能障碍的影响。方法将50只大白兔制成肠部分I/R损伤模型后,随机分为肠部分I/R损伤组(25只)、卡巴胆碱组[25只,于肠系膜上动脉(SMA)阻断后1h肠内注入3g/L卡巴胆碱(3μg/kg)]；另取25只设为假手术组,仅分离SMA,不阻断；取5只作为正常对照组,不致伤,处死后留取标本待测。检测兔SMA阻断前后及肠道内给予卡巴胆碱后肠黏膜的血流量。各致伤组均在处理后2、4、6、8、24、48、72h留取静脉血测定其血浆二胺氧化酶(DAO)活性及D-乳酸和D-木糖含量。并行葡聚糖蓝排出实验,以检测胃肠道吸收功能。同时选择大面积烧伤[烧伤总面积(84±12)%TBSA]患者8例,在患者肠呜音＜2次/min或腹胀明显时,口服1g/L卡巴胆碱(15μg/kg),观察给药后每分钟肠鸣音次数及腹胀情况。结果SMA阻断后肠部分I/R损伤组肠黏膜血流量为(48±6)PU,较正常对照组[(102±5)PU]明显减少,而肠道内注入卡巴胆碱后1h血流量增至(77±3)PU。肠缺血后肠部分I/R损伤组血浆DAO活性及D-乳酸含量开始升高,处理后24h达峰值[(4．63±0．27)U/ml、(7．9±2．4)mg/L],以后逐渐下降,但仍高于正常对照组[(0．89±0．14)U/ml、(2．0±1．1)mg/L,P＜0．05]。卡巴胆碱组的变化基本同肠部分I/R损伤组,但变化幅度较小；而假手术组则无明显变化(P＞0．05)。在给予D-木糖后2h,肠部分I/R损伤组血浆D-木糖含量显著降低,但处理后6h肠部分I/R损伤组及卡巴胆碱组明显升高,以后逐渐下降；假手术组略有波动。SMA处理后2h肠部分I/R损伤组葡聚糖蓝未见排出,处理后6h其运动距离逐渐增加,但处理后24h其运动距离仍明显短于正常值(P＜0．05),48～72h基本恢复正常；卡巴胆碱组注入葡聚糖蓝后即可见其排出,其运动距离明显增加,处理后6h达峰值(43±6)cm,以后逐渐缩短接近正常(28±3)cm。给药前患者肠呜音较弱(1．6±1．1)次/min,给药后10 min明显增强为(6．9±1．7)次/min,30 min时为(8．3±2．4)次/min,给药后1h患者肠鸣音仍较活跃,为(6．1±1．3)次/min。给药后2h患者腹胀明显减轻,其中有6例患者开始排便。结论肠内给予卡巴胆碱可增加兔肠黏膜血流量,改善其肠道运动、吸收、屏障功能；大面积烧伤患者口服卡巴胆碱,可改善其肠道功能障碍。

Influence of carbachol on intestinal dysfunction after traumatic or burn injury

OBJECTIVE: To investigate the influence of enteral administration of carbachol on the intestinal dysfunction of both severely burn patients and rabbits with partial intestinal ischemia/reperfusion (I/R) injury. METHODS: Seventy-five white rabbits were inflicted with I/R injury and randomized into intestinal I/R (I, n=25), carbachol [C, n=25, with 3g/L carbachol (3 mg/kg) injection into duodenum 1 h after SMA occlusion] and sham operation (SO, n=25, with SMA isolation but no occlusion) groups, and 5 other as normal controls. The blood flow of intestinal mucosa was detected before and after SMA occlusion or admission of carbachol. Changes in diamine oxidase (DAO), D-lactate, xylopyranose absorption, blue dextran discharging time were measured at 2, 4, 6, 8, 24, 48, 72 h after SMA occlusion. In addition, eight severe burn patients with TBSA of 84 +/- 12% were enrolled in the study, and carbachol (15 microg/kg) was administered to patients when abdominal distension or bowel sound was lower than 2times/min, then the number of abdominal distension and bowel sounds per minute were observed. RESULTS: The blood flow in intestinal mucosa of rabbits without SMA occlusion was (102 +/- 5) PU, reduced to (48 +/- 6) PU after SMA occlusion, and increased to (77 +/- 3) PU after injection of carbachol. The plsama DAO activity and D-lactic acid content in I group began to increase 4 hours after SMA occlusion, and they reached the peak 24 hours after SMA occlusion (4.63 +/- 0.27 U/ml, 7.9 +/- 2.4 mg/L) , after that they decreased gradually, but still higher than the normal value (0.89 +/- 0.14 U/ml, 2.0 +/- 1.1 mg/L, P < 0.05). In carbachol group, data showed the same trends as that in intestine I/R group with lower values, while no obvious changes were in sham operation group (P > 0.05). The content of D-lactic decreased dramatically 2 hours after D-lactic administration in both I and C groups, increased 6 hours after SMA occlusion, then decreased gradually, but it in C group was always higher than normal values, and little fluctuation was in sham operation group. There was no blue dextran discharge 2 hours after SMA occlusion. The discharging distance increased 6 hours later, but it was obviously shorter than the normal value 24 hrs after operation (P < 0.05) , then it returned to normal 48 to 72 hrs after operation. In the C group, blue dextran discharge was found immediately after its injection, with obvious increase in the discharging distance to peak value (43 +/- 6 cm) 6 hours after injury, and returning to normal (28 +/- 3 cm) gradually. In severe burned patients, the bowel sounds was (1.6 +/- 1.1) per minutes before carbachol administration, then increased dramatically to (6.9 +/- 1.7) per minutes 10 mins after administration, reached to a higher level 30 minutes after administration (8.3 +/- 2.4 ) times/min, and it maintained to (6.1 +/- 1.3) times/min 1 hour after administration. Abdominal distension was ameliorated 2 hours after carbachol administration, six patients were able to defecate. CONCLUSION: Enteral administration of Carbachol can increase the blood flow of intestine mucosa, help to improve the movement, absorption and barrier functions of intestine, and ameliorate intestinal dysfunction in patients with severe burns.