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作 者:孙海东[1] 邓敏[2] 苏霞[1] 潘微[1] Sun Haidong;Deng Min;Su Xia;Pan Wei(Department of Encephalopathy,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430000,Hubei Province,China)
机构地区:[1]武汉市中医医院脑病科,430000 [2]武汉市中医医院检验科
出 处:《中华老年心脑血管病杂志》2024年第4期455-459,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基 金:武汉市卫健委中医药科研项目(WZ22C67)。
摘 要:目的探究苦参碱调节高迁移率族蛋白B1(HMGB1)-晚期糖基化终末产物受体(RAGE)信号通路对缺血性脑卒中(IS)大鼠神经炎症的影响。方法将75只SD大鼠随机分为模型组、苦参碱低剂量组(10 mg/kg)、苦参碱高剂量组(20 mg/kg)、苦参碱高剂量+晚期糖基化终末产物(AGE)血清蛋白组(20 mg/kg苦参碱+100 mg/kg AGE血清蛋白)和假手术组,每组15只。采用线栓法构建大鼠大脑中动脉闭塞模型。用Longa评分评估大鼠神经功能缺损;氯化三苯四氮唑染色检测脑梗死情况;苏木精-伊红染色观察海马组织病理变化;酶联免疫吸附测定海马组织白细胞介素(IL)1β、IL-6、肿瘤坏死因子α(TNF-α)水平。Western blot检测海马组织HMGB1、RAGE蛋白表达。结果苦参碱高剂量组Longa评分、脑梗死面积、IL-1β、IL-6、TNF-α、HMGB1和RAGE蛋白表达明显低于模型组和苦参碱低剂量组(P<0.05)。苦参碱高剂量+AGE血清蛋白组Longa评分、脑梗死面积、IL-1β、IL-6、TNF-α、RAGE蛋白表达明显高于苦参碱高剂量组[(2.93±0.30)分vs(1.10±0.12)分,(38.18±4.04)%vs(15.52±1.74)%,(78.57±8.33)pg/ml vs(39.27±4.76)pg/ml,(203.14±24.39)pg/ml vs(92.45±11.23)pg/ml,(243.53±26.81)pg/ml vs(150.49±18.79)pg/ml,0.73±0.07 vs 0.44±0.04,P<0.05]。结论苦参碱可能通过抑制HMGB1-RAGE信号通路减轻IS大鼠的神经炎症。Objective To investigate the effect of matrine on neuroinflammation in ischemic stroke(IS)rats by regulating the high mobility group protein box1(HMGB1)-receptor for advanced glycation endproducts(RAGE)signaling pathway.Methods Seventy-five SPF-grade rats were randomly separated into model group,low-and high-dose matrine groups(10 and 20 mg/kg),high-dose matrine+advanced glycation end products(AGE,RAGE activator)group(20 mg/kg matrine+100 mg/kg AGE)and sham operation group,with 15 rats in each group.Thread occlusion method was applied to construct a rat model of middle cerebral artery occlusion(MCAO).Longa score was applied to score neurological deficits.TTC staining was used to measure cerebral infarction,and HE staining was employed to observe pathological changes in hippocampal tissue.ELISA was utilized to detect levels of IL-1β,IL-6,and TNF-αin hippocampal tissue.Western blotting was conducted to determine the protein levels of HMGB1 and RAGE in hippocampal tissue.Results Significantly lower Longa score,smaller cerebral infarct size,decreased levels of IL-1β,IL-6,TNF-α,and reduced protein levels of HMGB1 and RAGE were observed in high-dose matrine group than the model group and low-dose matrine group(P<0.05).High-dose matrine+AGE treatment resulted in increased Longa score,larger cerebral infarction size,and enhanced levels of IL-1β,IL-6,TNF-αand elevated RAGE protein level when compared with the simple high-dose matrine treatment[2.93±0.30 vs 1.10±0.12,(38.18±4.04)%vs(15.52±1.74)%,78.57±8.33 pg/ml vs 39.27±4.76 pg/ml,203.14±24.39 pg/ml vs 92.45±11.23 pg/ml,243.53±26.81 pg/ml vs 150.49±18.79 pg/ml,0.73±0.07 vs 0.44±0.04,P<0.05].Conclusion Matrine alleviates neuroinflammation in IS rats by inhibiting the HMGB1-RAGE signaling pathway.
关 键 词:苦参碱 卒中 大鼠 Sprague-Dawley 模型 动物 神经炎 HMGB1-RAGE信号通路
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