标题：miRNA-29b、MMP-2在大鼠颅内动脉瘤中的相关性及药物干预

      作者：彭浩，陈健龙，赵建农，王鹏程，张茂    (海南省人民医院神经外科，海南 海口 570311)

      卷次： 2017年28卷10期

      【摘要】 目的 观察miRNA-29b与MMP-2在颅内动脉瘤壁组织中的变化，探讨其在动脉瘤中的相关性及不同药物干预的影响。方法 将 40只雄性SD大鼠(6周龄)采用随机数字表法分为模型组、多西环素组、丙戊酸钠组和对照组，每组各 10只。模型组、多西环素组、丙戊酸钠组大鼠均采用颈外动脉结扎制造颅内动脉瘤模型，对照组大鼠不做造模处理。前三组于造模成功后分别注射生理盐水 0.1 mL/(kg·d)、多西环素 15 mg/(kg·d)、丙戊酸钠 15 mg/(kg·d)，对照组大鼠注射生理盐水0.1 mL/(kg·d)。2个月后取各组动脉组织，采用实时荧光定量PCR检测miRNA-29b的表达，采用免疫组化检测MMP-2的表达。结果 模型组、多西环素组、丙戊酸钠组和对照组中miRNA-29b的相对表达量分别为(0.27±0.04)，(0.68±0.03)，(0.47±0.15)，(0.95±0.12)，差异均有显著统计学意义(F=10.235，P<0.01)；miRNA-29b表达量经两两比较，模型组明显低于对照组，丙戊酸钠组明显高于模型组，而多西环素组明显高于丙戊酸钠组，差异均有统计学意义(P<0.05)；模型组、多西环素组、丙戊酸钠组和对照组中MMP-2阳性细胞数分别为(21.10 ± 3.36)，(10.27 ± 1.20)，(15.24 ±2.13)，(4.50±0.44)，差异均有显著统计学意义(F=6.013，P<0.01)；MMP-2阳性细胞数经两两比较，模型组明显高于对照组，丙戊酸钠组明显低于模型组，而多西环素组则明显低于丙戊酸钠组，差异均有统计学意义(P<0.05)。结论 miRNA-29b、MMP-2的表达水平与颅内动脉瘤的发生相关，多西环素对MMP-2的抑制作用明显强于丙戊酸钠。
      【关键词】 颅内动脉瘤；miRNA-29b；MMP-2；多西环素；丙戊酸钠
      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350（2017）10—1549—03

Correlation of miRNA-29b with MMP-2 in intracranial aneurysms of rats and drug intervention.
PENG Hao,CHEN Jian-long, ZHAO Jian-nong, WANG Peng-cheng, ZHANG Mao. Department of Neurosurgery, Hainan ProvincialPeople's Hospital, Haikou 570311, Hainan, CHINA
【Abstract】 Objective To observe the change of miRNA-29b and MMP-2 in the intracranial aneurysm walland their correlation, and to explore drug treatment in aneurysm. Methods Forty SD male rats of six weeks' old wererandomly divided into four groups: model group (n=10), doxycycline group (n=10), sodium valproate group (n=10),control group (n=10). The last three groups were performed ligation of the external carotid artery to establish intracrani-al aneurysm model, while rats in the control group were not treated. Then rats of the four groups were injected with sa-line 0.1 mL/(kg·d), doxycycline 15 mg/(kg·d), sodium valproate 200 mg/(kg·d), saline 0.1 mL/(kg·d) respectively af-ter establishing model successfully. After two months, the intracranial aneurysm tissue and normal arterial tissue weretaken. The expression of miRNA-29b was detected by real-time quantitative PCR (qPCR), and the expression ofMMP-2 was detected by immunohistochemistry. Results The expression of miRNA-29b in model group (0.27±0.04)was significantly lower than that in the control group (0.95±0.12); sodium valproate (0.47±0.15) significantly improves thelevel of miRNA-29b (as compared with the model group), and doxycycline (0.68±0.03) further improves the level signifi-cantly (as compared with the sodium valproate group); all the differences were statistically significant (P<0.05). The expres-sion of MMP-2 in the model group (21.10±3.36) was significantly higher than that in the control group (4.50±0.44); sodi-um valproate (15.24±2.13) significantly decreases the level of MMP-2 (as compared with the model group), and doxycy-cline (10.27±1.20) further decreases the level significantly (as compared with the sodium valproate group); all the differenceswere statistically significant (P<0.05). Conclusion The expression level of miRNA-29b and MMP-2 may be related to thedevelopment of intracranial aneurysms. And the inhibitory effect of doxycycline on MMP-2 was significantly stronger thansodium valproate.
      【Key words】 Intracranial aneurysm; miRNA-29b; MMP-2; Doxycycline; Sodium valproate·论 著·doi:10.3969/j.issn.1003-6350.2017.10.001基金项目：海南省自然科学基金(编号：20158354)