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硫化氢抑制大鼠颈总动脉球囊损伤后血管内膜增生的研究

Study of Inhibiting Effect of Hydrogen Sulfide on Vascular Intimal Hyperplasia after Balloon Injury in Rat Carotid Artery
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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。 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,H2S 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 14d and 28d sub - groups again. Af- ter modeling, the sham- operation group and control group were treated with intraperitoneal injection of normal saline every day. H2S group were treated with intraperitoneal injection of Sodium hydrogen sulfide(NariS) 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 H2S group in the same sub- groups decreased significantly (P 〈 0.05 ). Bcl- 2 expression decreased and Bax expression in- creased ( 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 - 6 in 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 signifi- cantly (P 〈 0.05). Bcl - 2 expression increased and Bax expression decreased (P 〈 0.05 ). Content of IL - 6 in 14 d sub - group in- creased ( P 〈 O. 05 ). Content of IL - 6 in 28 d sub - group did not have significant difference ( P 〉 0.05 ). Conclusion H2 S can allevi- ate 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 prolif- eration and the proliferation of VSMC induced through JAK/STAT pathway influenced by reducing the secretion of early IL - 6.
作者 姜宝平 夏勇
出处 《医学研究杂志》 2016年第12期85-89,共5页 Journal of Medical Research
关键词 硫化氢 PPG 球囊损伤 血管平滑肌细胞 H2S PPG Balloon injury Vascular smooth muscle cells
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