Effects of carbonyl sulfide in a rat model of limb ischemia/reperfusion-induced acute lung injury

doi:10.3969/j.issn.2095-4344.2016.40.010

Abstract

Abstract:

BACKGROUND: Previous studies have found that endogenous gaseous signaling molecules such as NO, CO, H₂S and SO₂ play an important role in acute lung injury; there also have other gases participation, such as carbonyl sulfide.

OBJECTIVE: To investigate the effect of carbonyl sulfide for limb ischemia-reperfusion induced acute lung injury and its mechanism in rats.

METHODS: A total of 64 Sprague-Dawley rats were randomly divided into eight groups. Control group: without treatment; model group: limb ischemia for 4 hours and then reperfusion for 2 hours. Low-, moderate- and high-dose carbonyl sulfide groups were intraperitoneally injected with 0.2, 0.5, 1.0 mL carbonyl sulfide respectively at 20 minutes before ischemia for 4 hours and reperfusion for 2 hours. Low-, moderate- and high-dose air groups were intraperitoneally injected with 0.4, 1.0, 2.0 mL air respectively at 20 minutes before ischemia for 4 hours and reperfusion for 2 hours. 2 hours after reperfusion, the morphological changes of lung tissues and the change of lung coefficient were observed. The expressions of tumor necrosis factor-a, interleukin-1β and interleukin-6 both in lung tissue and serum were detected by enzyme linked immunosorbent assay. Cell apoptosis was measured by TUNEL assay.

RESULTS AND CONCLUSION: (1) Compared with the control group, significant damage of lung tissue was seen, and the lung coefficient increased significantly in the model group (P < 0.05). The expressions of tumor necrosis factor-a, interleukin-l and interleukin-6 both in lung tissue and plasma increased (P < 0.05), and apoptotic rate increased. (2) Compared with the model group, low-, moderate- and high-doses of carbonyl sulfide could mitigate the degree of lung injury, and reduce pulmonary coefficient and apoptotic rate. The low dose showed the most obvious effect. Low- and moderate-dose carbonyl sulfide could significantly decrease expressions of tumor necrosis factor-a, interleukin-1β and interleukin-6 both in lung tissue and plasma (P < 0.05). (3) No significant difference in each index was visible in the low-, moderate- and high-dose air groups compared with the model group. (4) Results suggested that low dose of exogenous carbonyl sulfide through anti-inflammatory, anti-oxidant effects plays the protective role on limb ischemia/reperfusion-induced acute lung injury in rats.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

Key words: Acute Lung Injury, Models, Animal, Reperfusion Injury, Tissue Engineering

CLC Number:

R318

Zhao Yan-rui, Lv Wen-rui, Wang Dong, Zhou Jun-lin. Effects of carbonyl sulfide in a rat model of limb ischemia/reperfusion-induced acute lung injury[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(40): 5994-6000.

Figures/Tables 3

2.1 实验动物死亡率实验过程中，对照组、模型组及不同剂量空气组无实验动物死亡，存活率为100%。低剂量羰基硫组无实验动物死亡，中剂量羰基硫组死亡2只，死亡率为25%；高剂量羰基硫组死亡3只，死亡率为38%。 2.2 各组肺组织形态学变化光镜下观察可见对照组大鼠肺组织细、小支气管及肺泡结构正常，支气管黏膜上皮完整，见图1A；模型组肢体缺血4 h再灌注2 h后，肺组织出现间质水肿、肺泡增厚及中性粒细胞浸润的组织学变化，见图1B；应用羰基硫后(0.2，0.5，1 mL)肺组织学改变减轻，但低剂量羰基硫组改变最明显，见图1C-E；应用空气组未见明显减轻改变，见图1 F-H。 2.3 各组肺系数的变化与对照组相比，模型组肺系数显著增大(P < 0.01)；与模型组相比，羰基硫组均有改变，以低剂量羰基硫组肺系数改变最明显(P < 0.01)，高剂量羰基硫组改变较小；不同剂量空气组未见明显改变(P > 0.05)；与各剂量空气各组相比，各剂量羰基硫组(0.2，0.5 mL)肺系数改变明显(P < 0.01)，见表1。 2.4 各组肺组织及血浆中细胞因子水平的变化与对照组相比，模型组肺组织及血浆中白细胞介素1β、白细胞介素6和肿瘤坏死因子α含量均明显增加(P < 0.01)。与模型组相比，低、中剂量羰基硫组肺组织及血浆中的白细胞介素1β、白细胞介素6和肿瘤坏死因子α含量明显减少(P < 0.01)，高剂量羰基硫组改变不明显；各空气组肺组织及血浆中的白细胞介素1β、白细胞介素6和肿瘤坏死因子α含量无明显变化(P > 0.05)。与各空气组相比，低、中剂量羰基硫组肺组织及血浆中的白细胞介素1β、白细胞介素6和肿瘤坏死因子α含量明显减少(P < 0.01)，见表1。 2.5 各组TUNEL检测结果对照组中仅见少量凋亡细胞，凋亡指数为1.47%。与对照组相比，模型组凋亡细胞明显增加，凋亡指数达17.2%；与模型组相比，当应用羰基硫后，凋亡细胞明显减少，低、中、高剂量羰基硫组凋亡指数分别为5.83%、6.48%、7.88%；各空气组细胞凋亡未见明显减少，低、中、高剂量空气组凋亡指数分别为17.25%、17.65%、17.85%，见图2，3。"

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