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硫化氢对脂多糖诱导的大鼠肺动脉反应性及损伤的影响

[Effect of hydrogen sulfide on rat pulmonary artery reactivity and injury induced by lipopolysaccharide].

作者信息

Zhang Xiao-jing, Huang Xin-li, Meng Xiang-yan, Cong Bin, Dai Hong-yan, Wei Peng, Ling Yi-ling

机构信息

Faculty of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010 Aug;22(8):465-8.

Abstract

OBJECTIVE

To explore the effects of hydrogen sulfide (H2S) on abnormal pulmonary artery reactivity and injury induced by lipopolysaccharide (LPS).

METHODS

Seventy-two rats were divided into four groups randomly according to table of random number: control group, LPS group, sodium hydrosulfide (NaHS) as a donor of H2S+LPS group and NaHS+normal saline (NS) group (n=18 in each group). Rats were challenged with 0.8 ml/kg LPS (200 microg/200 microl) by intratracheal instillation. NaHS (28 micromol/kg, 0.5 ml) was injected intraperitoneally 10 minutes before LPS instillation and 2 hours after LPS instillation. Twelve hours later, 6 rats from each group were sacrificed. Blood from carotid artery was collected to detect H2S content in serum. After that, pulmonary artery rings (PARs) were prepared carefully, then the contraction response of PARs to phenylephrine (PE, 10(-6) mol/L) and the endothelium-dependent relaxation response to acetylcholine (ACh, 10(-6) mol/L) were measured using isolated vascular ring tension detecting technique. Six rats from each group were sacrificed for determination of malondialdehyde (MDA) content of pulmonary artery, and the remaining 6 rats from each group were sacrificed for observation of morphological changes in pulmonary artery tissue.

RESULTS

Compared with control group, after LPS instillation, the contraction response (g/mg) of PARs to PE increased greatly (0.86+/-0.20 vs. 0.56+/-0.13), the relaxation response to ACh significantly decreased [(65.18+/-7.05)% vs. (84.13+/-8.84)%]. MDA content (mmol/L) in pulmonary artery tissues increased (32.03+/-7.81 vs. 5.82+/-0.92), and H2S (micromol/L) content in serum decreased (175.23+/-27.36 vs. 238.12+/-16.38). Changes of all results were significant (P<0.05 or P<0.01). The pulmonary artery tissue and endothelium were injured. However, these changes were reversed by administration of NaHS intraperitoneally, the contraction response of PARs to PE decreased [(0.61+/-0.17) g/mg], the relaxation response to ACh increased [(82.92+/-9.71)%], MDA content in pulmonary artery tissue decreased [(16.88+/-3.54) mmol/L] and H2S content in serum increased [(242.70+/-38.80) micromol/L]. There was significant difference in all results (P<0.05 or P<0.01). The injury to the tissue induced by LPS were alleviated significantly. There was no statistical difference in above indexes between NaHS+NS group and control group, except for the level of H2S.

CONCLUSION

Exogenous H2S could not only reverse abnormal vascular reactivity of PARs induced by LPS but also alleviate the injury to pulmonary artery tissue induced by LPS.

摘要

目的

探讨硫化氢(H₂S)对脂多糖(LPS)诱导的肺动脉异常反应性及损伤的影响。

方法

将72只大鼠按随机数字表随机分为四组:对照组、LPS组、硫化氢供体硫氢化钠(NaHS)+LPS组和NaHS+生理盐水(NS)组(每组n = 18)。通过气管内滴注给予大鼠0.8 ml/kg LPS(200 μg/200 μl)。在滴注LPS前10分钟和滴注LPS后2小时腹腔注射NaHS(28 μmol/kg,0.5 ml)。12小时后,每组处死6只大鼠。采集颈动脉血检测血清中H₂S含量。之后,仔细制备肺动脉环(PARs),然后采用离体血管环张力检测技术测量PARs对去氧肾上腺素(PE,10⁻⁶ mol/L)的收缩反应及对乙酰胆碱(ACh,10⁻⁶ mol/L)的内皮依赖性舒张反应。每组另取6只大鼠处死,测定肺动脉丙二醛(MDA)含量,每组剩余6只大鼠处死,观察肺动脉组织形态学变化。

结果

与对照组相比,滴注LPS后,PARs对PE的收缩反应(g/mg)显著增加(0.86±0.20 vs. 0.56±0.13),对ACh的舒张反应显著降低[(65.18±7.05)% vs. (84.13±8.84)%]。肺动脉组织中MDA含量(mmol/L)增加(32.03±7.81 vs. 5.82±0.92),血清中H₂S(μmol/L)含量降低(175.23±27.36 vs. 238.12±16.38)。所有结果变化均有统计学意义(P<0.05或P<0.01)。肺动脉组织及内皮受损。然而,腹腔注射NaHS可逆转这些变化,PARs对PE的收缩反应降低[(0.61±0.17)g/mg],对ACh的舒张反应增加[(82.92±9.71)%],肺动脉组织中MDA含量降低[(16.88±3.54)mmol/L],血清中H₂S含量增加[(242.70±38.80)μmol/L]。所有结果均有显著差异(P<0.05或P<0.01)。LPS诱导的组织损伤明显减轻。除H₂S水平外,NaHS+NS组与对照组上述指标无统计学差异。

结论

外源性H₂S不仅可逆转LPS诱导的PARs血管反应异常,还可减轻LPS诱导的肺动脉组织损伤。

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