| 四氢生物蝶呤通过蛋白激酶Cε途径对醋酸脱氧皮质酮-盐型高血压小鼠左室舒张功能的影响 |
| Alternative Title | Tetrahydrobiopterin effects left ventricular diastolic function by upregulating protein kinase Cε signaling pathway in desoxycorticosterone acetate-salt hypertensive mice
|
| 许涵 |
| Thesis Advisor | 余静
|
| 2015-05-14
|
| Degree Grantor | 兰州大学
|
| Place of Conferral | 兰州
|
| Degree Name | 硕士
|
| Keyword | 四氢生物蝶呤
醋酸脱氧皮质酮-盐型高血压小鼠
高血压
左室舒张功能不全
蛋白激酶C ε
|
| Abstract | 目的：研究四氢生物蝶呤（BH4<下标!>）对醋酸脱氧皮质酮（DOCA）-盐型高血压小鼠左心室舒张功能与蛋白激酶C ε（PKC ε）表达的影响。
方法：90只C57BL/6小鼠随机分成高血压组（n=22）、高血压+BH4<下标!>组（n=22）、对照组（n=20）及对照+BH4<下标!>组（n=20）。四个亚组于术后21天时，分别进行以下实验测定：1.鼠尾动脉压测定小鼠舒张期血压（DBP）及收缩期血压（SBP）（n=10）。2.应用心脏彩超测定各组小鼠心脏结构及功能指标（n=10）。3.血流动力学测定小鼠Tau指数、舒张末期压力-容积关系（EDPVR）等指标（n=6）。
所有亚组均于术后22天时进行取材，所取组织均行酶联免疫实验、高效液相色谱法、放射免疫分析免法及Western-blot实验测定等测定。
结果：①高血压组与对照组相比，血压增高（P<0.05），高血压造模成功。②高血压组与对照组相比，E/E’、EDPVR及Tau指数增高（均P<0.05）③高血压组与对照组比较，SOD及NO减少（均P<0.05），给予BH4干预后，SOD及NO增多（均P<0.05）。④RT-PCR结果示高血压组与对照组相比，α-SA、PKC ε及β-MHC的表达减少(P<0.05)，给予BH4<下标!>干预后，α-SA、PKC ε及β-MHC的表达增加(P<0.05)。
结论 BH4<下标!>无明显的降压作用，但可改善左室舒张功能不全，这可能与其通过PKC ε途径降低体内氧化应激水平、提高NO表达等有关。 |
| Other Abstract | Objective To identify the influence of tetrahydrobiopterin (BH4) on left ventricular diastolic function and the expression of protein kinase C ε (PKC ε) in desoxycorticosterone acetate (DOCA)-salt hypertensive mice.
Method C57BL/6 mice were randomly divided into control group (n=22) 、control+BH4<下标!> group(n=22) 、SHAM group (n=20) and SHAM +BH4<下标!> group (n=20). At 21th day, all groups were experiments as follows: 1. Diastolic blood pressure(n=10). 2. The cardiac structural and functional parameters in hypertensive mice were measured by color doppler echocardiography and tissue doppler imaging(n=10). 3. The hemodynamic outcomes such as Tau index, end-diastolic pressure-volume relation (EDPVR) were tested by invasive hemodynamic monitor(n=6).
At 22th day after operation, all the mice were executed and cardiac tissues were experimented separately with following methods: ①Enzyme linked immunosorbent assay(ELASA). ②High-performance liquid chromatography(HPLC). ③Radioimmunoassay. ④Western-blot.
Results ①As compared to SHAM group, both SBP and DBP in control group were all increased(P<0.05). ②The E/E’, EDPVR and Tau index were increased in control group when compared with SHAM group(all P<0.05). ③ SOD and nitric oxide(NO) in control group were reduced when compared with SHAM group(all P<0.05), after gavaged with 2.5% BH4<下标!> , SOD and NO added(all P<0.05). ④When compared with SHAM group, α-SA, PKC ε and β-MHC in control group were decreased, but after intervened with BH4<下标!> , these genes express aggrandized(all P<0.05).
Conclusion BH4<下标!> had little effect on BP but could improve left ventricular diastolic dysfunction in hypertensive mice, which was related to lowering the levels of oxidative stress, increasing amounts of NO by up-regulated PKC ε signaling pathway. |
| URL | 查看原文
|
| Language | 中文
|
| Document Type | 学位论文
|
| Identifier | https://ir.lzu.edu.cn/handle/262010/222676
|
| Collection | 学院待认领
|
| Affiliation | 临床医学院
|
Recommended Citation
GB/T 7714 |
许涵. 四氢生物蝶呤通过蛋白激酶Cε途径对醋酸脱氧皮质酮-盐型高血压小鼠左室舒张功能的影响[D]. 兰州. 兰州大学,2015.
|
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
