一氧化氮对失血性休克大鼠离体淋巴管收缩性双相变化的调节作用

Nitric oxide modulates biphasic changes of isolated lymphatic contraction in hemorrhagic shock rats

本文旨在离体观察失血性休克后不同时间淋巴管的收缩性变化及一氧化氮(nitric oxide,NO)的作用。分离失血性休克进程中不同时间点(0,0.5,1,2,3h)的大鼠胸导管条,采用微血管压力-直径测定技术,离体观察淋巴管在不同跨壁压(1,3,5,7,9cmH2O)下的收缩频率(contraction frequency,CF)、收缩末期口径(end diastolic diameter,EDD)、舒张末期口径(end systolicdiameter,ESD)、被动管径(passive diameter,PD)的变化,计算淋巴管的收缩幅度(contraction amplitude,CA)、紧张性指数(tonicindex,TI)和泵流分数(fractional pump flow,FPF)。结果显示,在多个跨壁压下,休克0h、休克0.5h淋巴管的CF、TI、FPF显著高于对照组,随着休克的发展,休克2h和休克3h淋巴管在多个跨壁压下的CF、TI、FPF显著低于对照组。用NO相关的工具药单独或联合孵育休克0.5h和休克2h的淋巴管,然后在3cmH2O跨壁压条件下测定淋巴管的收缩性。NO供体L-Arg使休克0.5h淋巴管的CF、TI、FPF逆转至对照组水平,可溶性鸟苷酸环化酶抑制剂ODQ可抑制L-Arg的作用;相反地,NOS抑制剂L-NAME可提高休克2h淋巴管的CF、TI、FPF,磷酸二酯酶抑制剂氨茶碱则抑制L-NAME的作用。以上结果表明,失血性休克过程中淋巴管的收缩性呈双相变化,即早期收缩性增高,后期为低收缩性;NO在休克淋巴管收缩性双相变化中具有显著的调节作用。

The aim of the present study was to investigate the changes of lymphatic contraction after hemorrhagic shock in vitro and the underlying role of nitric oxide （NO）. Rat thoracic duct segments were isolated at 0, 0.5, 1, 2 and 3 h after hemorrhagic shock. Using Pressure Myograph System, we determined contraction frequency （CF）, end systolic diameter （ESD）, end diastolic diameter （EDD） and passive diameter （PD） of isolated rat lymphatics under different transmural pressures （1, 3, 5, 7 and 9 cmH 2 O）, then calculated contraction amplitude （CA）, tonic index （TI） and fractional pump flow （FPF） of lymphatics. The results showed that in several transmural pressures, lymphatic CF, TI and FPF were significantly higher in shock 0 h and shock 0.5 h groups than those in control group （sham operation group）. With the development of shock, lymphatic CF, TI and FPF decreased significantly in shock 2 h and shock 3 h groups compared with those in control group. We further discovered the role of NO in the changes of lymphatic contraction after hemorrhagic shock. Under 3 cmH 2 O transmural pressure, the changes of lymphatic contraction in shock 0.5 h and shock 2 h groups were analyzed following the incubation with several NO-related drugs alone or in combination. And the results showed that NO donor L-Arg reduced CF, TI and FPF in shock 0.5 h group to the control levels, while soluble guanylate cyclase inhibitor ODQ suppressed the effect of L-Arg. Moreover, NOS inhibitor L-NAME elevated the CF, TI and FPF of 2 h shock lymphatics to the control levels, while phosphodiesterase inhibitor aminophylline （AP） suppressed the effect of L-NAME. These results suggest that the lymphatic contractile activity exhibits a biphasic change during hemorrhagic shock, increasing in early phase and declining in later stage. And NO plays a major regulating role in the biphasic change of lymphatic contraction in hemorrhagic shock rats via cGMP pathway.