硫化氢对球囊损伤后兔颈动脉斑块和抗炎因子IL-10表达的影响

Effects of hydrogen sulfide on balloon injury-induced atherosclerotic plaque and IL-10 expression in rabbit carotid arteries

目的观察硫化氢(H2S)对高脂喂养兔颈总动脉球囊损伤术后动脉粥样硬化斑块形成及白细胞介素-10(IL-10)表达的影响。方法32只雄性新西兰大耳白兔随机均分为假手术组、模型组、硫氢化钠(NaHS)组[NaHS20μmol/(kg.d)]、炔丙基甘氨酸(PPG)组[PPG20mg/(kg.d)]。假手术组给予普通饲料,其他各组均以高脂饮食饲养并行颈总动脉内膜球囊损伤术建立动脉粥样硬化模型。8周后观察血浆H2S含量、损伤处血管组织病理学、免疫组化和血管内膜中膜厚度比值;Westernblotting和RT-PCR法检测颈动脉斑块IL-10的表达。结果与假手术组相比,模型组血浆H2S的含量显著减少(P<0.01),内膜显著增生(P<0.01),IL-10蛋白和基因表达差异无统计学意义(P>0.05);与模型组比较,NaHS组血浆H2S的含量显著升高(P<0.01),内膜增厚明显受到抑制(P<0.01),IL-10蛋白和基因表达明显增高(P<0.05);与假手术组、模型组比较,PPG组血浆H2S水平显著降低(P<0.05),损伤处血管内膜增生更为显著(P<0.05),IL-10蛋白和基因表达显著下降(P<0.05)。结论H2S可能通过上调粥样斑块内IL-10的表达发挥抗动脉粥样硬化的作用。

Objective To investigate the effects of hydrogen sulfide （H2S） on balloon injury-induced atherosclerotic plaque and IL-10 expression in rabbit carotid arteries.MethodsA total of 32 male New Zealand rabbits were randomly divided into 4 groups （8 each）：sham operation group,model group,NaHS group [NaHS 20μmol/（kg·d）] and PPG group [PPG 20mg/（kg·d）].Rabbits in sham operation group were fed with normal diet,while those in the other three groups were fed with high cholesterol food and underwent balloon injury operation after one week so that the atherosclerosis model was reproduced.Eight weeks later,the blood samples were collected from vein for detection of H2S level,and the injured vessel tissues were collected for pathological analysis.Immunohistochemical staining was done and the intima/media thickness ratio was investigated.Expression of IL-10 in carotid plaque was detected with Western blotting and RT-PCR.ResultsCompared with the sham operation group,serum H2S concentration in model group significantly decreased （P0.01）,and the tunica intima was obviously thickened （P0.01）,while no changes were found in the expression of IL-10 protein and gene （P0.05）.Compared with the model group,serum H2S concentration in NaHS group remarkably increased （P0.01）,the thickening of tunica intima was significantly suppressed （P0.01）,and the expression of IL-10 protein and gene increased significantly （P0.05）.In PPG group,the serum H2S concentration decreased （P0.05）,and the area of injured tunica intima thickened obviously （P0.05）,as compared with those in sham operation and model groups,whereas the expressions of IL-10 protein and gene were significantly decreased （P0.05）.ConclusionH2S may play a role in anti-AS by upregulation of IL-10 expression in atherosclerotic plaque.