清热化痰解毒方预处理对脑缺血再灌注损伤大鼠的保护作用及其对TXNIP/NLRP3通路的影响  被引量:15

Protective effects of Qingre Huayu Jiedu Decoction on cerebral ischemia-reperfusion injury in rats and its effect on TXNIP/NLRP3 pathway

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作  者:王涛[1] 刘宏祥[1] 王颖[1] 齐姣[1] 史小盼[1] 王丹[1] WANG Tao;LIU Hongxiang;WANG Ying;QI Jiao;SHI Xiaopan;WANG Dan(Department of Chinese and Western Medicine,Affiliated Hospital of Hebei University,Baoding,Hebei 071000,China)

机构地区:[1]河北大学附属医院中西医结合科,河北保定071000

出  处:《重庆医学》2018年第28期3605-3609,共5页Chongqing medicine

摘  要:目的探究清热化痰解毒方预处理对脑缺血再灌注损伤大鼠的保护作用及其对硫氧还蛋白结合蛋白(TXNIP)/NALP3炎性体(NALP3)通路的影响。方法大鼠按照随机数字表法分为假手术组,模型组(大脑中动脉线栓法制备),尼莫地平预处理组(8.0mg/kg),清热化痰解毒方低、中、高剂量预处理组,造模后对各组大鼠神经功能缺损进行评定,HE染色法观察各组大鼠脑组织病理学变化,RT-PCR、Western blot检测关节组织中TXNIP、NLRP3、白细胞介素1β(IL-1β)、凋亡相关斑点样蛋白(ASC)、半胱天冬酶1(caspase-1)表达。结果与假手术组相比,模型组神经功能缺损评分、大鼠脑梗死面积、NLRP3、IL-1β、ASC、caspase-1mRNA及TXNIP、NLRP3、IL-1β、ASC、caspase-1蛋白表达明显升高(P<0.05)。与模型组相比,尼莫地平组、清热化痰解毒方各组能明显降低神经功能缺损评分、大鼠脑梗死面积,呈剂量依赖性(P<0.05);与模型组相比,尼莫地平组、清热化痰解毒方各剂量组NLRP3、IL-1β、ASC、caspase-1 mRNA表达及TXNIP、NLRP3、IL-1β、ASC、caspase-1蛋白表达水平、蛋白阳性表达率明显降低,呈剂量依赖性,差异有统计学意义(P<0.05)。结论清热化痰解毒方预处理对脑缺血再灌注损伤大鼠大脑具有保护作用,可能与抑制TXNIP/NLRP3通路蛋白表达有关。Objective To investigate the protective effect of Qingre Huayu Jiedu decoction on cerebral ischemia-reperfusion injury in rats and its effect on thioredoxin-interacting protein(TXNIP)/NACHT-LRR-PYD-containing proteins-3(NALP3)pathway.Methods Rats were randomly divided into sham operation group,model group(prepared by middle cerebral artery suture-occluded method),Nimodipine pretreatment group(8.0 mg/kg),Qingre Huatan Jiedu Decoction low,middle and high dose pretreatment group.The neurological deficits of each group were evaluated after modeling.HE staining was used to observe the pathological changes of brain tissue in each group.RT-PCR and Western blot were used to detect TXNIP,NLRP3,IL-1β,Apoptosis-related spot-like protein(ASC)and caspase-1 expression in joint tissues.After making the model,the neurological deficit in each group was evaluated,the pathological changes of brain tissue in each group were observed by HE staining,RT-PCR and Western blot were used to detect the expressions of TXNIP,NLRP3,IL-1β,apoptosis related speckle like protein(ASC)and caspase-1 in joint tissues.Results Compared with the sham operation group,the neurological deficit scores,cerebral infarct size,NLRP3,IL-1β,ASC,caspase-1 mRNA expression and TXNIP,NLRP3,IL-1β,ASC,caspase-1 protein expression in the model group were significantly elevated(P<0.05).Compared with the model group,the neurological deficit scores and the infarct size of rats in the nimodipine group and Qingre Huayu Jiedu Decoction group were significantly decreased in a dose-dependent manner(P<0.05).Compared with the model group,the expressions of NLRP3,IL-1β,ASC and caspase-1 mRNA and the positive expression rates of TXNIP,NLRP3,IL-1β,ASC and caspase-1 protein in Nemodiping group and Qingre Huayu Jiedu Decoction group were significantly decreased in a dose-dependent manner.Conclusion Pretreatment with Qingre Huayu Jiedu Decoction has protective effects on the brain of rats with cerebral ischemia-reperfusion injury,which may be related to the inhibition of TXNIP/NL

关 键 词:清热化痰解毒方 脑缺血 再灌注损伤 硫氧还蛋白结合蛋白 NALP3炎性体 作用机制 

分 类 号:R285[医药卫生—中药学]

 

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