首页|白藜芦醇单用或与miR-27b激动剂联合应用对脑出血大鼠脑组织继发性病理损伤的防治作用观察

白藜芦醇单用或与miR-27b激动剂联合应用对脑出血大鼠脑组织继发性病理损伤的防治作用观察

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目的 观察白藜芦醇(Res)单用或与miR-27b激动剂联合应用对脑出血(ICH)大鼠脑组织继发性病理损伤的防治作用。方法 将180只雄性SD大鼠随机分为假手术组、ICH组、Res组、Res+miR-27b agomir组、NC组,每组36只。ICH组、Res组、Res+miR-27b agomir组以及NC组大鼠采用胶原酶注射尾状核法制备ICH模型。Res组、Res+miR-27b agomir组、NC组大鼠在造模前连续7 d 腹腔注射Res,假手术组及ICH组采注射等体积DMSO。Res+miR-27b agomir组大鼠在造模前3 d将miR-27b激动剂miR-27b agomir注入大鼠右侧脑室,NC组大鼠注射agomir阴性对照试剂,假手术组、ICH组、Res组注射等量生理盐水。各组大鼠造模成功后继续喂养24 h,使用mNSS评分量表评估神经功能。各组大鼠处死后取脑组织,采用TUNEL法测算脑组织神经细胞凋亡率,采用ELISA法检测大鼠脑组织炎症因子、氧化应激相关因子,采用qRT-PCR法检测大鼠脑组织中miR-27b、核因子相关因子2(Nrf2)mRNA,采用Western Blotting法检测大鼠脑组织中Nrf2/ARE信号通路相关蛋白Nrf2、血红素加氧酶(HO-1)、醌氧化还原酶1(Nqo1)。结果 假手术组大鼠mNSS评分、脑组织神经细胞凋亡率和TNF-α、IL-1β、MDA表达水平均低于其余各组(P均<0。05),SOD活力均高于其余各组(P均<0。05);ICH组大鼠mNSS评分、脑组织神经细胞凋亡率和TNF-α、IL-1β、MDA表达水平均高于其余各组(P均<0。05),SOD活力均低于其余各组(P均<0。05);且Res+miR-27b agomir组大鼠mNSS评分、脑组织神经细胞凋亡率和TNF-α、IL-1β、MDA表达水平均高于Res组和NC组(P均<0。05),SOD活力均低于Res组和NC组(P均<0。05)。与假手术组相比,ICH组、Res组、Res+miR-27b agomir组、NC组大鼠脑组织中miR-27b相对表达量均降低,Nrf2 mRNA和蛋白、HO-1蛋白、NQO1蛋白相对表达量均升高(P均<0。05);与ICH组相比,Res组、Res+miR-27b agomir组、NC组大鼠脑组织中miR-27b相对表达量均降低,Nrf2 mRNA和蛋白、HO-1蛋白、NQO1蛋白相对表达量均升高(P均<0。05);与Res+miR-27b agomir组相比,Res组、NC组大鼠脑组织中miR-27b相对表达量均降低,Nrf2 mRNA和蛋白、HO-1蛋白、NQO1蛋白相对表达量均升高(P均<0。05)。结论 Res单用或联合miR-27b激动剂可对ICH大鼠脑组织继发性病理损伤起防治作用,其防治作用可能与激活Nrf2/ARE信号通路有关。
Preventive and therapeutic effects of resveratrol alone or in combination with miR-27b agonist on secondary pathological injury of brain tissues in rats with ICH
Objective To observe the preventive and therapeutic effects of resveratrol(Res)alone or in combina-tion with miR-27b agonist on secondary pathological injury of brain tissues in rats with intracerebral hemorrhage(ICH).Methods Totally 180 male SD rats were randomly divided into the sham-operated group,the ICH group,the Res group,the Res+miR-27b agomir group,and the NC group,with 36 rats in each group.The rats in the ICH group,the Res group,the Res+miR-27b agomir group,and the NC group were used to establish the ICH models by collagenase injection of the caudate nucleus method.Rats in the Res,Res+miR-27b agomir,and NC groups were injected intraperitoneally with Res for 7 consecutive days before modeling,while rats in the sham-operated and ICH groups were injected with an equal vol-ume of DMSO.Rats in the Res+miR-27b agomir group were injected with the miR-27b agomir into the right ventricle of the rats for 3 d before modeling,while rats in the NC group were injected with agomir-negative control reagents.And rats in the sham operation,ICH,and Res groups were injected with equal volume of normal saline.After successful modeling,the rats in each group continued to receive feedings for 24 h.Neurological function was assessed by using the mNSS scor-ing scale.The brain tissues of rats in each group were taken after execution,and the apoptosis rate of neuronal cells in the brain tissues was measured by TUNEL method,while inflammatory factors and oxidative stress-related factors in the brain tissues of rats were detected by ELISA.Besides,qRT-PCR was used for the detection of miR-27b and nuclear factor-relat-ed factor 2(Nrf2)mRNA in the brain tissues of rats.Western blotting was used to detect the Nrf2/ARE signaling pathway-related proteins Nrf2,heme oxygenase(HO-1),and quinone oxidoreductase 1(Nqo1)in the brain tissues of rats.Re-sults The mNSS score,neuronal apoptosis rate of brain tissue,and the expression levels of TNF-α,IL-1β,and MDA in the sham-operated group were lower than those in the rest of the groups(all P<0.05),and the SOD activity was higher than those in the rest of groups(all P<0.05).The rat mNSS score,brain tissue neuronal cell apoptosis rate,and the ex-pression levels of TNF-α,IL-1β,and MDA were higher in the ICH group than in the rest of groups(all P<0.05),and the SOD activity was lower than the rest of the groups(all P<0.05).Moreover,the mNSS score,apoptosis rate of neuronal cells in the brain tissue and the expression levels of TNF-α,IL-1β and MDA were higher in the Res+miR-27b agomir group than in the Res group and the NC group(all P<0.05),while the SOD vitality was lower than those in the Res group and the NC group(all P<0.05).Compared with the sham-operated group,the relative expression of miR-27b decreased in the brain tissues of rats in the ICH group,the Res group,the Res+miR-27b agomir group,and the NC group,whereas the relative expression of Nrf2 mRNA and protein,HO-1 protein,and NQO1 protein increased(all P<0.05).In comparison with the ICH group,the relative expression of miR-27b in the brain tissues of rats in the Res group,the Res+miR-27b agomir group,and the NC group decreased,while the relative expression of Nrf2 mRNA and protein,HO-1 protein,and NQO1 protein all increased(all P<0.05).Compared with the Res+miR-27b agomir group,the relative expression of miR-27b decreased,while the relative expression levels of Nrf2 mRNA and protein,HO-1 protein,and NQO1 protein were ele-vated in the brain tissues of the rats in the Res group and the NC group(all P<0.05).Conclusion Res alone or in com-bination with miR-27b agomir has preventive effect on secondary pathological damage of brain tissue in rats with intracere-bral hemorrhage,and this effect may be associated with the activation of the Nrf2/ARE signaling pathway.

resveratrolintracerebral hemorrhagesecondary pathological injurymicroRNA-27bNrf2/ARE sig-naling pathway

舒艺璇、何晓英、陈鑫、蒋义碧

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西南医科大学附属医院神经内科,四川泸州 646000

白藜芦醇 脑出血 继发性病理损伤 微小RNA-27b Nrf2/ARE信号通路

2024

山东医药
山东卫生报刊社

山东医药

CSTPCD
影响因子:1.225
ISSN:1002-266X
年,卷(期):2024.64(9)
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