外源性硫化氢对兔自体移植静脉内膜增生的影响  

Effect of hydrogen sulfide on the intimal hyperplasia of vein grafts in rabbits

作　　者：蔡方刚[1] 许昌声[2] 吴捷[1] 何天敏[1] 陈篇章 Cai Fanggang;Xu Changsheng;Wu Jie;He Tianmin;Cheng Pianzhang(Department of Vascular Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China;Fujian Institute of Hypertension, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China)

机构地区：[1]福建医科大学附属第一医院血管外科,福州350005 [2]福建医科大学附属第一医院高血压研究所,福州350005

出　　处：《中华实验外科杂志》2019年第4期623-625,共3页Chinese Journal of Experimental Surgery

基　　金：福建省自然基金面上项目(2016J01536).

摘　　要：目的探讨外源性硫化氢(H2S)对兔自体移植静脉内膜增生的影响及其机制。方法采用兔自体颈静脉移植模型,40只新西兰大白兔随机分为5组,每组8只,分别为空白对照组(Ctr组)、单纯移植2周组、单纯移植4周组、移植+NaHS 2周组(NaHS:30 μmol/kg,每3 d 1次,连续给药2周)、移植+NaHS 4周组(NaHS:30 μmol/kg,每三天一次,连续给药4周)。苏木精-伊红(HE)染色观察各组自体静脉内膜增生的情况,酶联免疫吸附试验(ELISA)法检测各组血清H2S水平,应用实时定量聚合酶链反应(Real-time PCR)法检测各组移植静脉中内源性胱硫醚-γ-裂解酶(CSE) mRNA表达,Western blot法检测各组移植静脉中CSE、钙调蛋白(p-CaM/CaM)与Cyclin D1蛋白的表达。结果在供给NaHS后,移植静脉内的内膜增生明显减轻。移植+NaHS 2周组、移植+NaHS 4周组与相应的时间点比较,血清H2S水平均显著增高(33.65±4.10比23.56±4.82,P<0.05;36.50±4.62比23.72±3.95,P<0.05);CSE mRNA及蛋白相对表达量显著增高(mRNA:0.54±0.04比0.15±0.05,P<0.05;1.08±0.13比0.11±0.02,P<0.05;蛋白:0.56±0.06比0.47±0.03,P<0.05;1.14±0.07比0.38±0.04,P<0.05),差异有统计学意义。而p-CaM/CaM、Cyclin D1蛋白水平明显降低(p-CaM:0.25±0.05比0.52±0.06,P<0.05;1.21±0.09比2.39±0.15,P<0.05;CaM:0.42±0.04比0.73±0.07,P<0.05,0.47±0.05比1.17±0.06 P<0.05;Cyclin D1:0.28±0.06比0.95±0.11,P<0.05;0.29±0.04比1.02±0.10,P<0.05),差异有统计学意义。结论外源性硫化氢可以抑制移植静脉内膜增生,可能与其抑制移植静脉血管平滑肌细胞的p-CaM/CaM、Cyclin D1表达有关。Objective To observe the effect of exogenous hydrogen sulfide (H2S) on the intimal hyperplasia of vein grafts in rabbits and and its possible molecular mechanism. Methods Forty New Zealand rabbits were randomly divided into 5 group, including blank control group (Ctr group);two weeks of simple transplantation;four weeks of simple transplantation;transplantation + NaHS 2 weeks group (NaHS: 30 μmol/kg. 3 days, 2 weeks of continuous administration), transplantation + NaHS 4 weeks group (NaHS: 30 μmol/kg. 3 days, 4 weeks of continuous administration). Rabbit jugular vein transplantation animal model was established. Administration by intraperitoneal injection once 3 days. Serum H2S level was detected by enzyme linked immunosorbent assay (ELISA). The structure and hyperplasia of vascular tissue were observed by hematoxylin-eosin staining (HE) staining. real-time quantitative polymerase chain reaction (Real-time PCR) was used to determine the expression levels of cystathionine-gamma-lyase (CSE) mRNA. CSE, Calmodulin (p-CaM/ CaM)and Cyclin D1 protein levels were measured by Western blotting. Results After NaHS treatment, the intimal hyperplasia of vein grafts was relieved. Compared with the corresponding group, the serum H2S level increased in the transplantation + NaHS 2 weeks group and transplantation + NaHS 4weeks group (33.65±4.10 vs. 23.56±4.82, P<0.05;36.50±4.62 vs. 23.72±3.95, P<0.05). And the expression of CSE mRNA and protein increased significantly (mRNA: 0.54±0.04 vs. 0.15±0.05, P<0.05;1.08±0.13 vs. 0.11±0.02, P<0.05;Protein: 0.56±0.06 vs. 0.47±0.03, P<0.05;1.14±0.07 vs. 0.38±0.04, P<0.05). The expression of p-CaM/CaM and Cyclin D1 protein decreased significantly (p-CaM: 0.25±0.05 vs. 0.52±0.06, P<0.05;1.21±0.09 vs. 2.39±0.15, P<0.05;CaM: 0.42±0.04 vs. 0.73±0.07, P<0.05, 0.47±0.05 vs. 1.17±0.06 P<0.05;Cyclin D1: 0.28±0.06 vs. 0.95±0.11, P<0.05;0.29±0.04 vs. 1.02±0.10, P<0.05). Conclusion Exogenous hydrogen sulfide could inhibit the intima proliferation of vein grafts which related to

关 键 词：硫化氢 自体静脉 移植 内膜增生 

分 类 号：R654.4[医药卫生—外科学] R-332[医药卫生—临床医学]