新型气体信号分子硫化氢对低氧大鼠肺动脉平滑肌细胞凋亡的影响  

Effect of hydrogen sulfide, a new gaseous signal molecule, on pulmonary vascular smooth muscle cell apoptosis in rats

作　　者：陈晓波[1] 杜军保[1] 张春雨[1] 唐朝枢[2] 周伟仅[2] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院心血管研究所,北京100034

出　　处：《北京大学学报（医学版）》2004年第4期341-344,共4页Journal of Peking University:Health Sciences

基　　金：教育部教育振兴行动计划特殊专项 (九八五工程 ) ;国家自然科学基金 ( 3 0 2 713 73 ) ;教育部博士点科研基金项目资助( 2 0 0 2 0 0 0 10 63 ) ;国家重点基础研究发展规划 (G2 0 0 0 0 5 690 5 )~~

摘　　要：目的 :探讨新型气体信号分子硫化氢 (H2 S)对低氧大鼠肺动脉平滑肌细胞凋亡的调节作用。方法 :2 4只Wistar大鼠 ,随机分为对照组 (8只 )、低氧组 (8只 )和低氧 +NaHS组 (8只 )。以化学分光光度法测定血浆H2 S含量 ;采用原位缺口末端标记方法 (TUNEL)检测大鼠肺动脉平滑肌细胞的凋亡 ,并行图像分析计算单位面积细胞凋亡率 ;采用免疫组织化学方法检测肺动脉平滑肌细胞凋亡蛋白Bcl 2、Fas和caspase 3表达 ,并进行定位和半定量分析。结果 :低氧组与对照组比较 ,低氧组大鼠血浆中H2 S含量下降 36 % ,应用TUNEL检测肺动脉平滑肌细胞单位面积凋亡率减少 5 2 .9% ,肺动脉平滑肌细胞Bcl 2蛋白表达增高 1 2 3.9% ,Fas蛋白表达减弱 4 5 % ,caspase 3表达与对照组差异无显著性 ;低氧组与低氧 +NaHS组比较 ,低氧 +NaHS组大鼠血浆中H2 S含量升高 6 5 % ,应用TUNEL检测到肺动脉平滑肌细胞单位面积凋亡率较低氧组增高 6 2 .5 % ,肺动脉平滑肌细胞Bcl 2蛋白表达减弱 36 .4 % ,Fas和caspase 3蛋白表达分别增高 84 .8%、34.5 % ;结论 :低氧时肺动脉平滑肌细胞凋亡减少 ,H2 S可能通过抑制肺动脉平滑肌细胞Bcl 2蛋白表达、增加Fas和caspase 3蛋白表达 。Objective: To explore the effects of hydrogen sulfide (H 2S) on hypoxic pulmonary vascular smooth muscle cell (VSMC) apoptosis in rats. Methods: Twenty four Wistar rats were divided into 3 groups: control group ( n =8), hypoxia group ( n =8), and hypoxia +NaHS group ( n =8). The plasma level of H 2S was determined by methylene blue spectrophotometric method. VSMC apoptosis was measured by terminal deoxynucleotidyl transferase biotin nick end labeling (TUNEL). The protein expressions of Bcl 2, Fas and caspase 3 in pulmonary arteries were detected by immunohistochemical technique. Results: Compared with rats in the control group, the plasma level of H 2S decreased by 36% in rats of hypoxic group . The apoptotic rate per area in VSMCs detected with TUNEL was significantly decreased by 52.9% in rats of hypoxic group . The expressing integral score of Bcl 2 of VSMCs was increased by 123.9%,while Fas protein expression of VSMCs was decreased by 45% and caspase 3 protein expression of VSMCs was not significantly changed in rats of hypoxia group. But compared with rats in the hypoxia group, the plasma level of H 2S increased by 65% in rats of hypoxia+NaHS group. The apoptotic rate in VSMCs of TUNEL was significantly increased by 62.5% in rats of hypoxia+NaHS group. The Bcl 2 protein expression of VSMCs was decreased by 36.4% in rats of hypoxia+NaHS group. The expressing integral scores of Fas and caspase 3 were significantly higher in rats of hypoxia+NaHS group than in those of hypoxia group. Conclusion: Hypoxia decreased the pulmonary artery smooth muscle cell apoptosis. H 2S inhibited Bcl 2 protein expression of VSMCs and activated Fas and caspase-3 protein expressions of VSMCs, and therefore promoted the pulmonary artery smooth muscle cell apoptosis.

关 键 词：气体信号分子 硫化氢 低氧血症大鼠 肺动脉 平滑肌细胞 细胞凋亡 H2S 

分 类 号：R331.33[医药卫生—人体生理学]