玻璃體腔注射VAS2870對小鼠氧誘導視網膜病變的保護作用

郝艷芳，朱巧平，謝安明

?

·實驗論著·

玻璃體腔注射VAS2870對小鼠氧誘導視網膜病變的保護作用

郝艷芳1,2，朱巧平1,2，謝安明1

1Department of Ophthalmology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China;2Department of Ophthalmology, the First Hospital of Yulin, Yulin 719000, Shaanxi Province, China

?METHODS: Neonatal C57BL/6J mice were divided randomly into three groups: normoxic control group, PBS injection of OIR group and VAS2870 injection of OIR group. The mice of the latter two groups were exposed to 75% oxygen from the postnatal 7d (P7) to the postnatal 12d (P12) to induced OIR. VAS2870 was administered by intravitreal injection (0.5μL) in a mice model of OIR in P12. Another set of mice model of OIR were received a similar treatment with PBS. All eyes were collected at P17. The right eyes were whole mounted and stained with Lectin to observe the growth of retinal vessels; The eyes were enucleated to assess the levels of reactive oxygen species ROS/RNS. The expression of vascular endothelial growth factor (VEGF) and Nox4 mRNA were detected by western blot and RT-PCR, respectively.

?RESULTS: In the retina of OIR, VAS2870 reduced the retinal avascular area and neovascularization, the hypoxia-induced increase in ROS levels, the protein expression of VEGF and gene expression of Nox4 mRNA.

?CONCLUSION: NOX4 enzyme inhibition with VAS2870 has potent anti-oxidative stress effects in the retina, indicating its potential as a treatment for retinopathy of prematurity.

目的：觀察玻璃體腔注射VAS2870對C57小鼠氧誘導視網膜病變的影響。

方法：將新生C57BL/6J小鼠隨機分為3組，分別為正常對照組、VAS2870注射OIR組和無菌PBS緩沖液注射OIR組。將后兩組小鼠在出生后第7d(P7)至P12置于體積分數為75%±2%的恒定高氧氧箱中以構建OIR模型，在P12時給予幼鼠雙眼玻璃體腔注射VAS2870(0.5μL)，另一組幼鼠雙眼注射同等劑量的無菌PBS緩沖液。三組小鼠均在P17時取右眼行視網膜鋪片和Lectin染色，觀察視網膜中央無血管區及病理性新生血管的情況；取右眼行視網膜組織定量檢測ROS/RNS含量；取左眼應用RT-PCR檢測Nox4 mRNA含量，并應用Western-blot測定視網膜組織中VEGF的表達。

結果：VAS2870注射OIR組小鼠視網膜中央無血管區面積較無菌PBS緩沖液注射OIR組明顯減少(P<0.05)，病理性新生血管數目明顯減少(P<0.05)；VAS2870注射OIR組小鼠視網膜組織Nox4 mRNA的表達量明顯低于無菌PBS緩沖液注射組；VAS2870注射OIR組小鼠視網膜組織ROS含量較無菌PBS緩沖液注射組明顯降低(P<0.05)；VAS2870注射OIR組小鼠視網膜組織VEGF的表達明顯低于無菌PBS緩沖液注射組(P<0.05)。

結論：在小鼠OIR模型中，VAS2870可抑制Nox4 mRNA的表達，減少ROS/RNS，下調VEGF的生成，在視網膜病變進程中具有保護作用。

VAS2870；氧誘導視網膜病變；氧自由基；血管內皮生長因子

引用：郝艷芳，朱巧平，謝安明.玻璃體腔注射VAS2870對小鼠氧誘導視網膜病變的保護作用.國際眼科雜志2016;16(12):2200-2203

0引言

早產兒視網膜病變(retinopathy of prematurity，ROP)是一種多發生于早產兒或低體重嬰幼兒的視網膜增生性病變，與出生后暴露于波動氧誘導未發育成熟視網膜血管的收縮和閉塞形成無血管區并繼發病理性新生血管大量生成有著密切關系，后期可引起視網膜脫離，嚴重危害患兒的視力[1]。雖然在防治方面取得一些進展，但該病變一旦發生，進展很快，可有效治療的時間窗口很窄，仍無法有效地阻止病變的進展?！?br>