盐酸戊乙奎醚对创伤性休克兔肠组织诱导型一氧化氮合酶活性和一氧化氮含量的影响

Effect of penehyclidine hydrochloride on activity of inducible nitric oxide synthase and contents of nitric oxide in intestinal tissues of rabbits with traumatic shock

目的 研究盐酸戊乙奎醚（penehyclidine hydrochloride,PHC）对创伤性休克兔复苏后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,24只健康日本长耳大白兔,采用随机数字表法分为4组（每组6只）：对照组（Con组）、生理盐水复苏组（NS组）、PHC处理组（PHC组）、山莨菪碱（anisodamine,ANI）处理组（ANI组）.分别在休克前（T1）,休克末（T2）,复苏后即刻（T3）、2 h （T4）、4 h（T5）、6 h（T6）等6个时间点动态观察MAP和HR,实验结束后放血处死动物取小肠组织,观察肠组织中诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）活性和一氧化氮（nitric oxide,NO）含量的变化,光镜下检查组织病理学变化. 结果 各实验组动物T2时的MAP显著降低（均≤45 mmHg）（1 mmHg=0.133 kPa）;与Con组和PHC组比较,T3-T6时NS组的MAP显著低于T1时,差异有统计学意义（P＜0.05）.与Con组和PHC组比较,T3～T6时NS组的HR较T1时显著降低,差异有统计学意义（P＜0.05）;NS组、PHC组和ANI组肠组织iNOS活性[（4.39±0.44）、（1.59±0.49）、（1.62±0.62） U/mg]及NO含量[（5.81±0.27）、（2.10±0.24）、（2.15±0.30） μmol/g]与Con组[（0.70±0.24） U/mg、（0.70±0.32）μmol/g]比较,差异有统计学意义（P＜0.05）.NS组肠组织iNOS活性及NO含量显著高于PHC组、ANI组,差异有统计学意义（P＜0.05）.病理组织学检查显示PHC组和ANI组肠黏膜损伤较NS组显著减轻. 结论 PHC和ANI有助于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一定的保护作用,其作用机制可能是通过抑制iNOS活性,从而减少NO含量的生成而起作用的.

Objective 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 by Lamson＇s method.Twenty-four rabbits were randomly divided into control group （Con group）,traumatic shock with normal saline group （NS group）,traumatic shock treated with penehyclidine hydrochloride group（PHC group） and anisodamine group（ANI group）.At pre-shock （T1）,the end of shock（T2）,0（T3）,2 h（T4）,4 h（T5）,6 h（T6） after resuscitation,MAP and HR were monitored,intestinal tissue inducible nitric oxide synthase（iNOS） activity and nitric oxide（NO） concentration were measured by spectrophotometry.The pathological changes of tissue samples of the intestine were observed under microscope.Results At T2 time point,The level of MAP of rabbits in 4 experimental groups were prospectively decreased （≤45 mmHg）（1 mmHg=0.133 kPa）.Compared with PHC group and ANI group At T3-T6 time points,MAP in NS group was signifigantly lower than that before shock（P〈0.05）.At T3-T6 time points,HR in NS group was significantly lower than that at T1,also siginificangtly lower than that in the Con group and the PHC group （P〈0.05）.Compared with control group[（0.70±0.24） U/mg,（0.70±0.32） μmol/g],intestinal tissue iNOS activity[（4.39±0.44）,（1.59±0.49）,（1.62±0.62） U/mg]and NO concentration [（5.81±0.27）,（2.10±0.24）,（2.15±0.30） μmol/g] in NS group,PHC group and ANI group were significantly increased （P〈0.05）.intestinal tissue iNOS activity and NO concentration were significantly higher in NS group than those in PHC and ANI group （P〈0.05）.Conclusions PHC and ANI can stabilize hemodynamics in rabbits with traumatic shock.There was a protective effect on intestinal mucosa injury induced by traumatic shock.Inhibiting the iNOS activity and decreasing the NO contents might be related to the mechanism of protective effect during intestinal mucosa injury.