外源性硫化氢对肺移植大鼠肺血管功能改变的影响

doi:10.3877/cma.j.issn.2095-8773.2017.01.05

目的

探讨外源性硫化氢对肺移植大鼠再灌注早期肺血管功能改变的影响。

方法

雄性SD大鼠随机分为对照组(假手术)、肺移植组和硫化氢-肺移植组，每组10只。硫化氢-肺移植组：于移植肺肺门开放前5 min腹腔注入外源性硫化氢(NaHS)14 μmol/kg，再灌注2 h后处死大鼠，取左肺组织检测肺湿干比(W/D)、丙二醛(MDA)和髓过氧化物酶(MPO)含量以及诱导型一氧化氮合酶(iNOS)。取大鼠肺动脉行离体血管环实验，分别比较血管环舒张和收缩功能功能。

结果

与对照组比较，肺移植组大鼠肺组织的W/D比值升高，MDA含量、MPO、iNOS活性增加，差异有统计学意义(P<0.05)；与肺移植组比较，硫化氢-肺移植组大鼠肺组织的W/D比值降低，MDA含量、MPO、iNOS活性降低，差异均有统计学意义(P<0.05)。与对照组比较，肺移植组离体肺动脉对乙酰胆碱引起的内皮依赖的舒张反应降低，差异有统计学意义(P<0.05)；而使用NaHS处理后，硫化氢-肺移植组的血管舒张效应恢复到对照组水平(P>0.05)。与对照组比较，肺移植组离体肺动脉的收缩功能下降，差异有统计学意义(P<0.05)；使用NaHS处理后硫化氢-肺移植组的血管收缩功能无明显改变(P>0.05)。

结论

外源性硫化氢不仅能够减少肺移植后的氧化应激和炎症反应，抑制iNOS活性的增加，减轻缺血再灌注损伤，而且能够增强移植后离体肺血管的舒张功能。

关键词: 硫化氢, 肺移植, 缺血再灌注损伤, 离体肺动脉, 一氧化氮合酶

Objective

To investigate the effects of hydrogen sulfide on function change of isolated pulmonary artery in rat lung transplantation model.

Methods

Male SD rats were randomly divided into control group(sham operation group), lung transplantation group and lung transplantation+ hydrogen sulfide group, with 10 rats in each group. In hydrogen sulfide+ lung transplantation group, orthotopic left lung allograft transplantation was performed, and hydrogen sulfide 14 μmol/kg was injected intraperitoneally at the beginning of reperfusion. Rats were sacrificed 2 h after reperfusion, and left lung tissues were harvested to determine the wet dry ratio (W/D), content of malondialdehyde (MDA) and activity of myeloperoxidase(MPO) and inducible nitric oxide synthase (iNOS). Isolated pulmonary artery rings were prepared, and the vasodilation and contraction function of pulmonary artery rings were compared.

Results

The W/D, MDA content and activity of MPO and iNOS in lung transplantation group were significantly higher than those in control group(P<0.05). The W/D, MDA content and activity of MPO and iNOS in lung transplantation+ hydrogen sulfide group were significantly lower than those in lung transplantation group (P<0.05). Compared with control group, the endothelium-dependent vasodilation function of isolated pulmonary artery significantly decreased in lung transplantation group (P<0.05), but after hydrogen sulfide treatment, the vasodilation function restored to the level in control group (P>0.05). The contraction function of isolated pulmonary artery in lung transplantation group was significantly lower than that in control group (P<0.05), but there was no significant change in contraction function of isolated pulmonary artery in lung transplantation+ hydrogen sulfide group (P>0.05).

Conclusions

Hydrogen sulfide can alleviate the oxidative stress and inflammatory reaction, inhibit the activity of iNOS, reduce the ischemia-reperfusion injury after lung transplantation, and improve the vasodilation function of isolated pulmonary artery after transplantation.

Key words: Hydrogen sulfide, Lung transplantation, Ischemia-reperfusion injury, isolated pulmonary artery, nitric oxide synthase

图1 NaHS预处理对肺移植大鼠离体肺血管环去氧肾上腺素浓度反应曲线(A)和乙酰胆碱的浓度反应曲线(B)的影响。肺移植组与对照组比较，各浓度点均有统计学差异(P < 0.05)。

表1 三组W/D、MPO、MDA、iNOS和eNOS含量比较(±s，n＝10)

组别		W/D	MDA(ng/ml)	MPO(ng/ml)	iNOS(ng/ml)	eNOS(ng/ml)
对照组^①		4.2±0.5	13.3±0.5	1.0±0.2	0.3±0.1	0.7±0.2
肺移植组^②		5.2±0.3	21.2±4.2	1.2±0.1	0.8±0.1	0.3±0.1
硫化氢-肺移植组^③		4.6±0.3	16.3±2.1	1.1±0.1	0.5±0.1	0.5±0.1
①与②比较		?	?	?	?	?
?	t值	－5.42	－5.91	－2.83	－11.18	5.66
?	P值	P<0.05	P<0.05	P<0.05	P<0.05	P<0.05
②与③比较		?	?	?	?	?
?	t值	4.47	3.30	2.24	6.71	－4.47
?	P值	P<0.05	P<0.05	P<0.05	P<0.05	P<0.05

表1 三组W/D、MPO、MDA、iNOS和eNOS含量比较(±s，n＝10)

组别		W/D	MDA(ng/ml)	MPO(ng/ml)	iNOS(ng/ml)	eNOS(ng/ml)
对照组^①		4.2±0.5	13.3±0.5	1.0±0.2	0.3±0.1	0.7±0.2
肺移植组^②		5.2±0.3	21.2±4.2	1.2±0.1	0.8±0.1	0.3±0.1
硫化氢-肺移植组^③		4.6±0.3	16.3±2.1	1.1±0.1	0.5±0.1	0.5±0.1
①与②比较		?	?	?	?	?
?	t值	－5.42	－5.91	－2.83	－11.18	5.66
?	P值	P<0.05	P<0.05	P<0.05	P<0.05	P<0.05
②与③比较		?	?	?	?	?
?	t值	4.47	3.30	2.24	6.71	－4.47
?	P值	P<0.05	P<0.05	P<0.05	P<0.05	P<0.05

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Effects of hydrogen sulfide on function change of isolated pulmonary artery in rat lung transplantation model

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Effects of hydrogen sulfide on function change of isolated pulmonary artery in rat lung transplantation model