MEDLINE/PubMed Journal Browser Search

Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

Title: [Paclitaxel enhances the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged rat].
Author: Guo H, Zheng M, Jiao YB, Zheng H.
Journal: Zhonghua Xin Xue Guan Bing Za Zhi; 2018 Sep 24; 46(9):719-724. PubMed ID: 30293379.
Abstract:
Objective: To investigate if paclitaxel can enhance the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged ratand explore related mechanism. Methods: Primary cardiomyocytes of Sprague-Dawley rats were isolated by trypsin and divided into 5 groups(n=6 each): control group, hypoxia injury group, hypoxia preconditioning group, paclitaxel group,and paclitaxel+hypoxia preconditioning group. The structure of microtubules and the expression of hypoxia-inducible factor-1α(HIF-1α) were analyzed by immunofluorescence staining. The Langendorff isolated heart perfusion model was applied in 4 groups: hypoxia reperfusion injury group, hypoxia preconditioning group, paclitaxel group, and paclitaxel+hypoxia preconditioning group. Each group was further divided into elderly subgroup and adult subgroup (n=6 each). Left ventricular developed pressure and maximum rate of rise in left ventricular pressure were analyzed. Results: (1) Primary cardiomyocyte experiments showed that the myocardial tubular microtubule structure in control group was intact and evenly stained; most of the microtubules in the hypoxia-injured group were absent and the tubular tissue was broken; the hypoxia-induced damage on microtubule structure was smaller in the hypoxic preconditioning group compared with the hypoxic injury group (microtubule staining was not uniform, and the lattice structure was broken, but not that obvious as in the hypoxia group); the tubular structure of the microtubules of the paclitaxel group was basically complete, and the staining was basically uniform.The integrity of tubular structure was maintained to some extent, similar to a normal microtubule structure in paclitaxel+hypoxia preconditioning group. The expression of HIF-1α in the cytoplasm and nucleus was very low in the control group, which was evidenced in both cytoplasm and nucleus in the hypoxic injury group.The expression was further increased in hypoxic preconditioning group, significant nuclear HIF-1 expression was found in the paclitaxel group, the expression was aggregated in the nucleus in the Paclitaxel+ hypoxia preconditioning group. (2)In Langendorff isolated heart perfusion model, left ventricular developed pressure was similar between the elderly subgroup and the adult subgroup at the end of the infusion,after precondition, 5 minutes of reperfusion, 30 minutes of reperfusion, and 60 minutes of reperfusion in the hypoxic injury group (all P> 0.05).In the hypoxic injury group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((15.63±4.88) mmHg (1 mmHg=0.133 kPa) vs. (95.63±22.14)mmHg and (17.31±2.75)mmHg vs. (91.00±9.58)mmHg, respectively,all P<0.05). In the hypoxic preconditioning group, the adult subgroup had higher left ventricular developed pressure at 5 and 30 minutes of reperfusion when compared with the elderly subgroup((7.13±1.02) mmHg vs. (3.75±1.06)mmHg and (43.94±3.21)mmHg vs.(16.31±1.54)mmHg, respectively,all P<0.01). In the paclitaxel group, the adult subgroup had higher left ventricular developed pressure at 30 and 60 minutes of reperfusion when compared with the elderly subgroup((44.31±7.59)mmHg vs. (5.44±1.21)mmHg, (51.56±6.03)mmHg vs. (22.19±5.14)mmHg, respectively, all P<0.01). In the paclitaxel+hypoxia preconditioning group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((18.63±4.30)mmHg vs. (99.94±8.23) mmHg, P<0.01; (49.69±5.34)mmHg vs. (95.31±5.26)mmHg, P<0.05). Meanwhile, the adult subgroup had higher left ventricular developed pressure at 30 minutes of reperfusion when compared with the elderly subgroup((49.69±5.34)mmHg vs. (18.63±4.33)mmHg, P<0.01).The adult subgroup had higher change rate of maximum rate of rise in left ventricular pressure at 60 minutes of reperfusion when compared with the elderly subgroup in hypoxia preconditioning group, paclitaxel group, and paclitaxel combined hypoxia preconditioning group((62.83±3.92)% vs. (33.33±3.20)%, (44.17±2.32)% vs. (36.67±2.88)%, (72.50±2.66)% vs. (53.17±2.56)%, respectively,all P<0.01). Conclusion: Paclitaxel can enhance the myocardial protective effect of myocardial ischemia preconditioning through stabilizing microtubules of cardiomyocytes and promoting HIF-1α localization in the nucleus. 目的： 探讨紫杉醇是否能够增强心肌缺氧预处理对老年大鼠心肌缺血再灌注损伤的保护作用及其机制。 方法： 将Sprague-Dawley大鼠原代心肌细胞分为对照组、缺氧损伤组、缺氧预处理组、紫杉醇组和紫杉醇联合缺氧预处理组（均n=6），采用免疫荧光染色法分析心肌细胞微管结构以及缺氧诱导因子-1α（HIF-1α）表达情况。另外，建立Langendorff离体心脏灌流模型,并分为缺氧再灌注损伤组、缺氧预处理组、紫杉醇组和紫杉醇联合缺氧预处理组，每组再分为老年亚组和成年亚组（每组均为6只Sprague-Dawley大鼠），记录左心室发展压和左心室内压最大上升速率。 结果： （1）原代心肌细胞实验显示，对照组心肌细胞微管管状结构完整，染色均匀；缺氧损伤组细胞大部分微管结构缺失，管状组织断裂；缺氧预处理组细胞微管结构损伤较缺氧损伤组损伤小，微管染色不均匀，网格状结构断裂，但不明显；紫杉醇组细胞微管管状结构基本完成，染色基本均匀；缺氧预处理联合紫衫醇组细胞微管管状结构具有一定的完整性，类似正常微管结构。对照组心肌细胞胞浆和细胞核中HIF-1α表达量很少；缺氧损伤组HIF-1α在细胞质及细胞核中均有表达；缺氧预处理组细胞核中HIF-1α表达量较多；紫杉醇组HIF-1α入核表达增强；紫杉醇联合缺氧预处理组大量HIF-1α聚集在细胞核内，细胞质中分布较少。（2）在Langendorff离体心脏灌流模型中，缺氧再灌注损伤组老年亚组与成年亚组的左心室发展压在平衡灌注末、预处理后、再灌注5 min、再灌注30 min和再灌注60 min差异均无统计学意义（P均>0.05）；在缺氧损伤组中，老年亚组和成年亚组的再灌注30 min左心室发展压均低于平衡灌注末[分别为（15.63±4.88）mmHg（1 mmHg=0.133 kPa）比（95.63±22.14）mmHg和（17.31±2.75）mmHg比（91.00±9.58）mmHg，P均<0.05]。在缺氧预处理组中，成年亚组再灌注5和30 min的左心室发展压均高于老年亚组[分别为（7.13±1.02）mmHg比（3.75±1.06）mmHg和（43.94±3.21）mmHg比（16.31±1.54）mmHg，P均<0.01]。在紫杉醇组中，成年亚组再灌注30和60 min的左心室发展压均高于老年亚组[分别为（44.31±7.59）mmHg比（5.44±1.21）mmHg和（51.56±6.03）mmHg比（22.19±5.14）mmHg，P均<0.01]。在紫杉醇联合缺氧预处理组中，老年亚组和成年亚组再灌注30 min左心室发展压均低于平衡灌注末[分别为（18.63±4.30）mmHg比（99.94±8.23）mmHg，P<0.01；（49.69±5.34）mmHg比（95.31±5.26）mmHg，P<0.05]；成年亚组再灌注30 min的左心室发展压高于老年亚组[（49.69±5.34）mmHg比（18.63±4.33）mmHg，P<0.01]。缺氧预处理组、紫杉醇组和紫杉醇联合缺氧预处理组的成年亚组再灌注60 min左心室内压最大上升速率变化比率均高于老年亚组[分别为（62.83±3.92）%比（33.33±3.20）%，（44.17±2.32）%比（36.67±2.88）%，（72.50±2.66）%比（53.17±2.56）%，P均<0.01]。 结论： 紫杉醇能够增强老年大鼠心肌组织缺血预处理的心肌保护作用，其机制是通过稳定微管结构而促进HIF-1α核转位。.

[Abstract] [Full Text] [Related] [New Search]