miR-153 通过 Shh 信号通路对 MCAO 大鼠血管生成的影响。
Effects of miR-153 on angiogenesis in MCAO rats through Shh signaling pathway.
机构信息
Department of Neurology, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):732-739. doi: 10.26355/eurrev_201901_16887.
OBJECTIVE
Cerebrovascular disease is a disease which has the highest mortality in China. Angiogenesis in the ischemic region after cerebral infarction is closely related to its prognosis. Recent studies found that microRNAs (miRNAs) are involved in the regulation of neovascularization. MicroRNA-153 (MiR-153) has protective effects on the ischemic injury, but its relationship with the Sonic Hedgehog (Shh) signaling pathway is still unclear. This work aimed to investigate the role of miR-153 in angiogenesis of middle cerebral artery occlusion (MCAO) rats through the Shh signaling pathway.
MATERIALS AND METHODS
The rat cerebral ischemic injury (MCAO) model was established by thread embolism and treated by Agomir-153 and 5-EI. MiR-153 expression was detected using Real Time-Polymerase Chain Reaction (RT-PCR). The neurological function was assessed. The infarct area of the brain and the capillary density were determined using 2,3,5-triphenyl tetrazolium chloride (TTC) method. The Shh signaling pathway and angiogenesis-related factors were tested by Western blot assay.
RESULTS
Agomir-153 or Agomir-153 combined with 5-EI significantly increased miR-153 expression, reduced the infarct area, and promoted the generation of cerebral capillaries in the MCAO model. 5-EI partially blocked the protective effects of Agomir-153 and angiogenesis. The up-regulation of miR-153 markedly inhibited patched (PTC) expression and activated the Shh signaling pathway.
CONCLUSIONS
The up-regulation of miR-153 rats activated the Shh signaling pathway to promote angiogenesis and improve prognosis through lipid-coated Patch (PTC) in MCAO. MiR-153 was considered to be a new therapeutic target for promoting angiogenesis after MCAO.
目的
脑血管病是中国死亡率最高的疾病。脑梗死缺血区的血管生成与其预后密切相关。最近的研究发现，微小 RNA（miRNA）参与了新生血管的调节。miR-153（MiR-153）对缺血性损伤具有保护作用，但它与 Sonic Hedgehog（Shh）信号通路的关系尚不清楚。本研究旨在通过 Shh 信号通路探讨 miR-153 在大脑中动脉闭塞（MCAO）大鼠血管生成中的作用。
材料和方法
采用线栓栓塞法建立大鼠脑缺血损伤（MCAO）模型，并采用 Agomir-153 和 5-EI 进行治疗。采用实时聚合酶链反应（RT-PCR）检测 miR-153 的表达。评估神经功能。采用 2,3,5-三苯基氯化四氮唑（TTC）法测定脑梗死面积和毛细血管密度。采用 Western blot 法检测 Shh 信号通路及血管生成相关因子。
结果
Agomir-153 或 Agomir-153 联合 5-EI 可显著增加 miR-153 的表达，减少 MCAO 模型中的梗死面积，并促进脑毛细血管的生成。5-EI 部分阻断了 Agomir-153 的保护作用和血管生成。miR-153 的上调显著抑制 patched（PTC）的表达并激活 Shh 信号通路。
结论
上调 miR-153 可激活 Shh 信号通路，通过 MCAO 中的脂包被 Patch（PTC）促进血管生成，改善预后。miR-153 被认为是 MCAO 后促进血管生成的新治疗靶点。
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