天麻素调控miR-181b对创伤性颅脑损伤大鼠行为及脑水肿的作用机制探究OACSTPCD
The mechanism of Gastrodin on behavior and brain edema in rats with traumatic brain injury by regulating miR-181b
目的 探究天麻素(GAS)调控miR-181b对创伤性颅脑损伤(TBI)大鼠行为及脑水肿的作用机制.方法 将120只SPF级SD雄性大鼠随机分为假手术组(Sham组)、TBI模型组(Model组)、低剂量GAS 组(GAS-L 组,50 mg/kg GAS)、高剂量 GAS 组(GAS-H 组,100 mg/kg GAS)、高剂量 GAS+miR-181b antagomir NC 组(GAS-H+miR-181b antagomir NC 组,100 mg/kg GAS+200 nmol miR-181b antagomir NC)和高剂量 GAS+miR-181b antagomir 组(GAS-H+miR-181b antagomir 组,100 mg/kg GAS+200 nmol miR-181b antagomir),每组20只大鼠.采用改良神经功能缺损严重程度评分量表(mNSS)对各组大鼠神经功能进行评估.采用转棒测试、旷场实验评价大鼠行为学变化.干湿重法测定大鼠脑组织含水量.HE染色观察大鼠脑组织病理学变化.实时荧光定量PCR(RT-qPCR)法测定各组大鼠脑组织miR-181b水平.Western blot法测定大鼠脑组织中基质金属蛋白酶-9(MMP-9)、水通道蛋白-4(AQP-4)的表达水平.结果 与Sham组相比,Model组大鼠mNSS评分、脑组织含水量、脑组织MMP-9、AQP4蛋白表达显著升高(P＜0.05),转棒测试跌落时间、旷场实验区域中心停留时间、脑组织miR-181b水平显著降低(P＜0.05),大鼠脑皮质神经元萎缩,结构紊乱,细胞轮廓不清晰,出现严重的脑损伤.与Model组相比,GAS-H组大鼠相关指标变化趋势与上述相反(P＜0.05).miR-181b antagomir减弱了 GAS对TBI导致的大鼠行为学障碍和脑水肿的减轻作用.结论 GAS可能通过提高miR-181b的表达来改善TBI导致的大鼠行为学障碍和脑水肿.
Objective To investigate the mechanism by which Gastrodin(GAS)regulates miR-181b in rats with traumatic brain injury(TBI)and its effects on behavior and brain edema.Methods 120 SPF-grade male SD rats were randomly divided into Sham group,Model group(TBI model),low-dose GAS group(GAS-L group,50 mg/kg GAS),high-dose GAS group(GAS-H group,100 mg/kg GAS),high-dose GAS+miR-181b antagomir NC group(GAS-H+miR-181b antagomir NC group,100 mg/kg GAS+200 nmol miR-181b antagomir NC),and high-dose GAS+miR-181 b antagomir group(GAS-H+miR-181b antagomir group,100 mg/kg GAS+200 nmol miR-181b antagomir),with 20 rats in each group.Modified neurological severity scores(mNSS)were used to assess the neurologi-cal function of rats.Rotarod test and open field test were employed to evaluate behavioral changes.Brain tissue water con-tent was measured using the wet-dry method.Histopathological changes in rat brain tissues were observed through HE staining.Real-time fluorescent quantitative PCR(RT-qPCR)was used to determine miR-181b levels in rat brain tis-sues.Western blot was performed to assess the expression levels of matrix metalloproteinase(MMP)-9 and aquaporin(AQP)-4 in rat brain tissues.Results Compared with the Sham group,rats in the Model group showed significantly in-creased mNSS scores,brain tissue water content,expression of MMP-9 and AQP4 in brain tissues(P＜0.05),de-creased fall time in the rotarod test,reduced central stay time in the open field test,and decreased miR-181 b levels in brain tissues(P＜0.05).Neurons in the rat cerebral cortex were atrophied,structurally disordered,and cell contours were unclear,indicating severe brain damage.Compared with the Model group,rats in the GAS-H group showed oppo-site trends in the above indicators(P＜0.05).miR-181b antagomir attenuated the alleviating effects of GAS on TBI-induced behavioral disorders and brain edema.Conclusion GAS may improve TBI-induced behavioral disorders and brain edema in rats by upregulating the expression of miR-181b.
朱刚毅;朱义通;陆兆丰
河南科技大学第一附属医院开元急诊科(河南洛阳 471000)
中医学
天麻素miR-181b创伤性颅脑损伤脑水肿
GastrodinmiR-181btraumatic brain injurybrain edema
《广东医学》 2024 (006)
685-691 / 7
河南省医学科技攻关计划项目(SBGJ202102198);河南省医学教育研究项目(Wjlx2021389)
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