冬凌草甲素调控大鼠脑出血后NLRP3炎性小体表达的作用及机制研究  

Effect and mechanism of oridonin on NLRP3 inflammasome expression after intracerebral haemorrhage in rats

作　　者：邓柏春 顾应江 刘玉洲 蔡昱 DENG Baichun;GU Yingjiang;LIU Yuzhou;CAI Yu(The Affiliated TCM Hospital of Southwest Medical University,Luzhou 646000,Sichuan,China)

机构地区：[1]西南医科大学附属中医医院,四川泸州646000

出　　处：《西部医学》2025年第4期511-517,共7页Medical Journal of West China

基　　金：西南医科大学附属中医医院引进人才专项基金([2019]119)。

摘　　要：目的研究冬凌草甲素(Ori)调控NLRP3炎性小体表达对脑出血(ICH)大鼠的神经保护作用及可能机制。方法120只SPF级健康雄性大鼠采用随机数字表法将实验大鼠随机分成假手术组、模型组、溶剂组及治疗组,每组30只。通过在右侧尾状核区立体定向注射Ⅶ型细菌胶原酶制备ICH大鼠模型。干预后,在第1、3、7天使用改良神经功能缺损评分(mNSS)评价神经功能缺损情况,在第1、3天通过干湿比重法分析脑水含量,苏木精-伊红染色(HE)染色观察病理改变,尼氏染色统计神经元存活情况,酶联免疫吸附试验(ELISA)检测IL-1β、IL-18的含量,免疫荧光及蛋白印迹检测ASC、Caspase-Ⅰ及NLRP3的蛋白表达。结果予以Ori治疗大鼠第1天时神经功能缺损症状改善不明显(P>0.05),第3、7天神经功能缺损症状改善明显(P<0.05)。与模型组相比,治疗组大鼠第1、3天大鼠脑水肿减轻(P<0.05),存活神经元数增多(P<0.05)。与模型组相比,第1天时治疗组Caspase-Ⅰ的蛋白水平,IL-1β、IL-18含量无明显差异(P>0.05),第3天时治疗组脑组织ASC、脑组织Caspase-Ⅰ及NLRP3蛋白水平,IL-1β、IL-18含量降低(P<0.05)。结论冬凌草甲素可减轻脑出血大鼠的神经炎症反应,减轻脑水肿和神经元损伤,改善神经功能缺损症状,其潜在机制能是通过抑制NLRP3炎性小体的激活实现的。Objective To study the neuroprotective effect of oridonin(Ori)regulating NLRP3 inflammasome expression in rats with intracerebral haemorrhage(ICH)and its possible mechanism.Methods The rats were randomly divided into sham operation group,model group,solvent group and treatment group by random number table method.ICH rat model was prepared by stereotactic injection of bacterial collagenaseⅦinto the right caudate nucleus.After the intervention,neurological impairment was evaluated by mNSS on the 1st,3rd and 7th day,cerebral water content was analyzed by dry-wet specific gravity method on the 1st and 3rd day,hematoxylin-eosin staining(HE)was used to observe pathological changes.The neuronal survival was analyzed by nissl staining,and IL-1βand IL-18 were detected by Enzyme-Linked immunosorbent assay(ELISA).The protein expressions of ASC,caspase-I and NLRP3 were detected by immunofluorescence and western blot(WB).Results The neurological deficits of the rats were improved by Ori treatment on day 3 and 7(P<0.05),but not on day 1(P>0.05).Compared with model group,brain edema was reduced(P<0.05),the number of viable neurons increased in treatment group at day 1 and 3(P<0.05).On day 3,the protein expression of ASC,caspase-Ⅰand NLRP3 and the content of IL-1βand IL-18 were significantly decreased in treatment group(P<0.05),but there was no significant difference in caspase-Ⅰprotein expression,IL-1β,IL-18 content on day(P>0.05).Conclusion Oridonin can reduce neuroinflammatory response,cerebral edema,neuronal injury and neurological impairment in rats with ICH.The underlying mechanism can be realized by inhibiting the activation of NLRP3 inflammasome.

关 键 词：脑出血 冬凌草甲素 NLRP3炎性小体 炎症反应 

分 类 号：R285[医药卫生—中药学] R743.34[医药卫生—中医学]