【摘要】 目的探讨硫化氢(hydrogen sulfide,H2S)供体对球囊损伤大鼠颈总动脉后血管新生内膜面积(neointimal area,NA)、血清白细胞介素-6(interleukin-6,IL-6)和内膜B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响。方法假手术组作为正常参照,用球囊损伤对照组、H2S组和PPG组大鼠的颈总动脉,各组12只,每组再平均分为14天和28天两个亚组。建模后,假手术组和对照组每天用生理盐水腹腔注射,H2S组每天用硫氢化钠(sodium hydrogen sulfide,Na HS)溶液(2.8mg/kg)经腹腔注射给药,PPG组每天用炔丙基甘氨酸(propargylglycine,PPG-内源性H2S生成抑制剂)药物(37.5mg/kg)经腹腔注射给药。预定时间点,观察管腔病理改变、ELISA检测IL-6的含量和免疫组化法测Bcl-2与Bax蛋白的表达。结果与对照组相比,相同亚组的H2S组NA及内膜中膜比(neointimal area/medial area,NA/MA)均明显减小(P<0.05),Bcl-2表达减弱,Bax表达增强(P<0.05),14天亚组IL-6含量减低(P<0.05),28天亚组IL-6含量差异无统计学意义(P>0.05)。与对照组相比,相同亚组的PPG组NA及NA/MA显著增加(P<0.05),Bcl-2表达增强,Bax表达减弱(P<0.05),14天亚组IL-6含量增加(P<0.05),28天亚组IL-6含量差异无统计学意义(P>0.05)。结论 H2S可以减轻损伤后血管的狭窄,其作用机制可能包括通过影响Bcl-2蛋白和Bax蛋白表达,从而使血管损伤后增殖和迁移至内膜的血管平滑肌细胞(vascular smooth uscle cell,VSMC)凋亡大于增殖和通过减少早期IL-6的分泌来影响IL-6通过JAK/STAT通路诱导的VSMC的增殖。更多还原

【Abstract】 Objective Discuss influence of hydrogen sulfide(H2S) donor on rats with balloon injury in carotid artery in terms of neointimal area(NA),serum Interleukin-6(IL-6).B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax)expression.Methods Sham-operation group was taken as the normal reference.Control group,H2 S group and PPG group were treated with balloon injury in carotid artery.There are 12 rats in each group and each group was divided into 14 d and 28 d sub-groups again.After modeling,the sham-operation group and control group were treated with intraperitoneal injection of normal saline every day.H2 S group were treated with intraperitoneal injection of Sodium hydrogen sulfide(Na HS) solution(2.8mg/kg) every day.PPG group were treated with intraperitoneal injection of Propargylglycine(PPG-endogenous H2S-generated inhibitor)(37.5mg/kg).At the scheduled time,the luminal pathologic change was observed,content of IL-6 were determined by ELISA,and Bcl-2 and Bax protein expression were measured with immunohistochemical method.Results Compared to the control group,NA and neointimal area/medial area(NA/MA) of H2 S group in the same sub-groups decreased significantly(P < 0.05).Bcl-2 expression decreased and Bax expression increased(P < 0.05).Content of IL-6 in 14 d sub-group decreased(P < 0.05).There is no significant difference in content of IL-6in 28 d sub-group(P > 0.05).Compared to the control group,NA and NA/MA of PPG group in the same sub-group increased significantly(P < 0.05).Bcl-2 expression increased and Bax expression decreased(P < 0.05).Content of IL-6 in 14 d sub-group increased(P < 0.05).Content of IL-6 in 28 d sub-group did not have significant difference(P > 0.05).Conclusion H2 S can alleviate the vascular stenosis after balloon injury.The mechanism of action is possibly that apoptosis of vascular smooth muscle cell(VSMC)of the proliferated and migrated vessels after damaged through influencing Bcl-2 protein and Bax protein expression is greater than proliferation and the proliferation of VSMC induced through JAK/STAT pathway influenced by reducing the secretion of early IL-6.更多还原