胸部大動脈瘤ラットにおけるmiR-22-3pとMMP-9の発現変化とその意義。

Changes in expressions of miR-22-3p and MMP-9 in rats with thoracic aortic aneurysm and their significance.

• H-M Zhao
• L Jin
• Y Liu
• X Hong

抄録

目的:

本研究の目的は、胸部大動脈瘤ラットにおけるマイクロリボ核酸（miR）-22-3pとマトリックスメタロプロテアーゼ-9（MMP-9）の発現変化とその意義を探ることであった。

OBJECTIVE: The purpose of this study was to explore the changes in the expressions of micro ribonucleic acid (miR)-22-3p and matrix metalloproteinase-9 (MMP-9) in rats with thoracic aortic aneurysm (TAA) and their significance.

材料および方法:

特定病原体を含まないSprague-Dawley雌ラット16匹を、正常群（n=8）とアンジオテンシンII（Ang II）群（n=8）に無作為に分けた。Ang II群ではマイクロポンプを用いてAng IIを灌流し、正常群では同量の正常生理食塩水を灌流した。連続介入後、胸部大動脈の腫瘍形成速度を観察し、両群ともに逆転写ポリメラーゼ連鎖反応（RT-PCR）によりmiR-22-3pの発現を検出した。他の16匹のラットを選択し、無作為にagomiR-22-3p群(n=8)と対照群(n=8)に分けた。agomiR-22-3p群では、agomiR-22とAng IIを角静脈を介して連続的に注入した。対照群では、agomiR陰性対照を注射し、Ang IIを連続的に灌流した。4週間の介入後、胸部大動脈の腫瘍形成率を観察し、両群ともに免疫蛍光および免疫組織化学によりMMP-9の発現を決定した。

MATERIALS AND METHODS: A total of 16 specific pathogen-free Sprague-Dawley female rats were randomly divided into normal group (n=8) and angiotensin II (Ang II) group (n=8). Ang II was perfused using the micro pump in Ang II group, while the same amount of normal saline was perfused in the normal group. After continuous intervention, the tumor formation rate in the thoracic aorta was observed, and the expression of miR-22-3p was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in both groups. Other 16 rats were selected and randomly divided into agomiR-22-3p group (n=8) and control group (n=8). In the agomiR-22-3p group, agomiR-22 and Ang II were continuously injected via angular vein. In the control group, agomiR negative control was injected, and Ang II was continuously perfused. After intervention for 4 weeks, the tumor formation rate in the thoracic aorta was observed, and the expression of MMP-9 was determined via immunofluorescence and immunohistochemistry in both groups.

結果:

4週間の介入後、Ang II群では正常群に比べてmiR-22-3pの発現が有意に低下した（p<0.05）。4週間の薬剤投与後、agomiR-22-3p群は対照群に比べて腫瘍形成率が低く(p<0.05)、MMP-9の発現も低かった(p<0.05)。

RESULTS: After intervention for 4 weeks, the expression of miR-22-3p in Ang II group was significantly lower than that in normal group (p<0.05). After drug administration for 4 weeks, agomiR-22-3p group had a lower tumor formation rate (p<0.05) and a lower expression of MMP-9 than the control group (p<0.05).

結論:

TAAラットではmiR-22-3pの発現が低下し、miR-22-3pはMMP-9の発現を阻害することで、ラットにおけるTAAの形成を抑制することができる。

CONCLUSIONS: The expression of miR-22-3p declines in TAA rats, and miR-22-3p can inhibit the expression of MMP-9, thus suppressing the formation of TAA in rats.