Expression of vascular growth factors during the early phase of induced cerebral aneurysm formation in rats

doi:10.3969/j.issn.2095-4344.2014.49.016

Abstract

Abstract:

BACKGROUND: Vascular endothelial growth factor and transforming growth factor play a crucial role in embryonic development, wound healing, inflammation, cancer, ischemic hypoxia and other physiological and pathological processes, and participate in the development and progression of brain damage.

OBJECTIVE: To evaluate the differences in the expression of vascular endothelial growth factor and transforming growth factor-α during the early phase of cerebral aneurysm formation in rats.

METHODS:Twenty-eight healthy Sprague-Dawley rats were randomized into three groups. Sham operation group (n=8): the left carotid artery bifurcation and bilateral renal artery were only exposed, without ligation, and rats were killed that day. 15 days group (n=10) and 30 days group (n=10): the left common carotid artery, internal carotid artery, external carotid artery and bilateral renal artery were ligated, to establish aneurysm model, and rats were killed at 15 and 30 days, respectively. The bilateral sides of the anterior cerebral artery/olfactory artery bifurcations were harvested and observed under light microscopy for pathological changes. Immunohistological staining was performed to detect the expression of vascular endothelial growth factor and transforming growth factor-α.

RESULTS AND CONCLUSION: The results showed that, no aneurysm formed in the sham operation group and 15 days group. In the 30 days group, one saccular aneurysm and five early aneurysm-like changes were found in the right anterior cerebral artery/olfactory artery bifurcations. In the sham operation group and 15 days group, no vascular endothelial growth factor was expressed. In the 30 days group, the positive rate of vascular endothelial growth factor was up to 80%, indicating that vascular endothelial growth factor is possibly involved in the formation of aneurysm. Transforming growth factor-α expression in the sham operation group and 15 days group was more apparent than that in the 30 days group, indicating that transforming growth factor-α is damaged or secretion is reduced in this process, which was possibly related to the formation of aneurysm.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: intracranial aneurysm, vascular endothelial growth factors, transforming growth factor-α

CLC Number:

R318

Li Shao-shan, Wang Zeng-liang, Serick•Duysenbi, Wang Yong-xin, Cheng Xiao-jiang, Zhou Qing-jiu, . Expression of vascular growth factors during the early phase of induced cerebral aneurysm formation in rats [J]. Chinese Journal of Tissue Engineering Research, 2014, 18(49): 7961-7966.

Figures/Tables 1

2.1 各组动脉瘤形成位置、常规染色和血压变化各组大鼠术后无死亡。假手术组8只和15 d组10只大鼠双侧大脑前动脉和嗅动脉分叉处均未见有动脉瘤。30 d组10只大鼠中发现在右侧大脑前嗅动脉分叉处1个囊性动脉瘤和5个早期动脉瘤样改变(图1A)，其中囊性动脉瘤为进展期动脉瘤，在高倍光镜下都可见到内弹力层的断裂、肌肉层的变薄及动脉壁的往外膨出；早期动脉瘤性改变5只，表现为内弹力层的不连续性，没有明显的动脉壁的往外膨出(图1B，C)。假手术组血压为(93.05±4.45) mm Hg (1 mm Hg= 0.133 kPa)。15 d组和30 d组手术当天血压分别为(94.28±6.95)，(101.10±4.56) mm Hg，造模15 d时的血压分别为(128.58±4.54)，(130.76±6.89) mm Hg，较假手术组血压显著升高(P = 0.005)，2周后两组血压稳步上升(P = 0.05)；1个月后30 d组血压(186.89±6.78) mm Hg，明显上升(P = 0.05)。 2.2 各组大鼠血管因子的表达结果血管内皮生长因子表达：血管内皮生长因子在正常血管壁(图2A)和诱导动脉瘤形成15 d时(图2B)无表达，血管内皮生长因子免疫组织化学染色均无染色；到30 d时，在10个脑动脉标本中8个为血管内皮生长因子阳性(80%)(图2C)，平均染色分级为0.5±0.1，主要分布在内皮下层，3组间平均染分级比较差异有显著性意义(F=11.2，P=0.005)。转化生长因子α表达：转化生长因子α在正常血管壁中有表达(图3A)，在检测的8个正常脑动脉标本中转化生长因子α呈全阳性(100%)，其中4个标本中呈强染色，另外4个标本中呈明显染色，平均染色分级为2.3±0.4；到诱导动脉瘤形成15 d时，在检测的10个脑动脉标本中转化生长因子α呈全阳性(图3B)，其中7个标本中染色清晰，3个标本中染色弱，平均染色分级为2.1±0.2；到30 d时，在检测的10个脑动脉标本中表达阳性率为90%(图3C)，6个标本染色弱，3个标本染色清晰，另外1个标本无染色，平均染色分级1.5±0.1，3组间平均染色分级比较差异有显著性意义(F=11.2，P=0.005)。"

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