摘要
背景:研究表明莫诺苷在大鼠缺血性脑损伤模型中具有抗炎、抗氧化、抗凋亡、促进血管和神经再生、抗血小板聚集和神经保护作用,但莫诺苷是否可以抑制脑出血的炎症反应尚不清楚。目的:观察不同剂量的莫诺苷对大鼠脑出血后炎症因子白细胞介素1、肿瘤坏死因子α和炎症相关蛋白NF-κB和SUMO2/3的影响及神经功能变化。方法:将健康雄性SD大鼠随机分为假手术组、脑出血和莫诺苷低、中、高剂量组,后4组大鼠采用自体尾动脉血注入法建立脑出血模型,术后莫诺苷低、中、高剂量组分别给予莫诺苷30,90,270 mg/kg每天3次灌胃给药,连续7 d,假手术组和模型组给予等量生理盐水。给药7 d后应用NSS评分观察各组大鼠神经功能缺损症状;评分后取大鼠血肿周围脑组织,苏木精-伊红染色观察血肿周围神经细胞形态结构的变化;ELISA法检测大鼠脑组织炎症因子白细胞介素1、肿瘤坏死因子α水平;免疫组化法及Western blotting法检测通道蛋白NF-κB和SUMO2/3蛋白的表达。结果与结论:(1)与脑出血组比较,莫诺苷低、中、高剂量组神经功能缺损改善,其中高剂量组改善最明显(P<0.05);(2)与假手术比较,脑出血组和莫诺苷低、中、高剂量组神经功能受损,炎症因子白细胞介素1、肿瘤坏死因子α和炎症相关蛋白NF-κB、SUMO2/3表达增多(P<0.05);(3)与脑出血组比较,莫诺苷低、中、高剂量组炎症因子白细胞介素1、肿瘤坏死因子α表达减少,炎症相关蛋白NF-κB降低,SUMO2/3表达增多(P<0.05),以高剂量组作用最明显(P<0.05)。提示:高剂量莫诺苷可通过炎症调节蛋白的变化,下调炎症因子的表达,抑制炎症反应改善脑出血大鼠的神经功能。
BACKGROUND:Morroniside has been shown to play roles of anti-inflammation,antioxidant,anti-apoptosis,promoting vascular and neural regeneration,anti-platelet aggregation and neuroprotection in the rat model of ischemic brain injury,but whether it can inhibit the inflammatory reaction of cerebral hemorrhage is unclear.OBJECTIVE:To observe the changes of inflammatory factors(interleukin-1,tumor necrosis factor-α)and inflammatory-related proteins(nuclear factor-κB and SUMO2/3)as well as neurologic function in a rat model of cerebral hemorrhage treated with morroniside at different doses.METHODS:Healthy male Sprague-Dawley rats were randomly divided into sham operation,cerebral hemorrhage and low-,medium-and high-dose morroniside groups.The model of cerebral hemorrhage was established in the latter four groups by injecting autologous blood from the tail artery,followed by intragastric injection of 30,90,270 mg/kg morroniside in the three morronicide groups,respectively,three times daily for consecutive 7 days;the rats in the sham operation and model groups were given same volume of normal saline.Then,the neurological function was evaluated by Neurological Severity Scores;the brain tissue around the hematoma were removed to observe the morphological changes of neurocytes around the hematoma by hematoxylin-eosin staining;the expression levels of interleukin-1 and tumor necrosis factorαin the brain tissue were detected by ELISA;the expression levels of nuclear factor-κB and SUMO2/3 were detected by immunohistochemistry and western blot assay.RESULTS AND CONCLUSION:Compared with the icerebral hemorrhage group,the low-,medium-and high-dose morroniside groups showed a significnat neurological improvement,especially the high-dose group(P<0.05).Compared with the sham operation group,the cerebral hemorrhage and morroniside groups exhibited a significant increase in the nerve function damage and expression levels of interleukin-1,tumor necrosis factorα,nuclear factor-κB and SUMO2/3(P<0.05).Compared with the cerebral hemorrhage group,in the low-,medium-and high-dose morroniside groups,the expression levels of interleukin-1 and tumor necrosis factorαwere significantly reduced,and expression levels of nuclear factor-κB and SUMO2/3 were significantly increased(P<0.05).In summary,high-dose morroniside can improve the neurological function in rats with cerebral hemorrhage by down-regulating the levels of inflammatory cytokines.
作者
袁志俊
何晓英
袁平
郑晓梅
李小刚
Yuan Zhi-jun;He Xiao-ying;Yuan Ping;Zheng Xiao-mei;Li Xiao-gang(Department of Neurology,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2018年第8期1217-1222,共6页
Chinese Journal of Tissue Engineering Research
基金
四川省卫生厅科研项目(110368)~~
