硫化氢对血管性痴呆大鼠缺血再灌注损伤中NLRP3表达的影响

目的探讨硫化氢(H₃S)对血管性痴呆(VaD)大鼠缺血再灌注损伤(IRI)中NLRP3表达的影响。方法采用改良四血管法(4-VO)制作VaD大鼠IRI模型,随机数字表法将大鼠分为假手术组、模型组、抑制剂组(CY-09组)、NaHS组,每组各6只,共24只大鼠。应用Morris水迷宫实验评价大鼠学习记忆能力,收集各组大鼠脑组织标本,采用苏木素-伊红(HE)染色,观察海马区形态。各组大鼠血清H₃S含量采用亚甲蓝法检测;白细胞介素(IL)-1β、IL-18采用酶联免疫吸附试验(ELISA)检测;用Western印迹检测各组大鼠海马组织中炎症小体NLRP3、Caspase-1表达水平。结果VaD大鼠模型构建成功;模型组大鼠海马区神经元细胞损伤明显,海马组织NLRP3、Caspase-1蛋白相对表达量显著增加(P<0.05)。NaHS组大鼠海马区神经元细胞损伤减轻,血清H₃S含量较模型组明显升高(P<0.05),海马组织NLRP3、Caspase-1蛋白较模型组降低(P<0.05);CY-09组大鼠海马区神经元细胞损伤减轻,海马组织NLRP3、Caspase-1蛋白较模型组降低(P<0.05),血清IL-1β、IL-18显著低于模型组(P<0.05)。结论VaD大鼠IRI可引起NLRP3表达增加;H₃S能够通过降低NLRP3表达,减轻大鼠IRI。

Effect of hydrogen sulfide on the expression of NLRP3 in vascular dementia rats with ischemia-reperfusion injury

Objective To investigate the effect of hydrogen sulfide(H₃S)on the expression of NLRP3 in vascular dementia(VaD)rats with ischemia-reperfusion injury(IRI).Methods The IRI model of VaD rats was made by modified four vessel method(4-vo).The rats were randomly divided into sham operation group,model group,inhibitor(CY-09)group and NaHS group,with 6 rats in each group and 24 rats in total.Morris water maze test was used to evaluate the learning and memory ability of rats.Brain tissue samples were collected and hematoxylin eosin staining(HE)was used to observe the morphology of hippocampus.The levels of serum H₃S,IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA),and the expressions of NLRP3 and Caspase-1 in hippocampus were detected by Western blotting.Results VaD rat model was successfully established;neuron cell damage was obvious in the hippocampus of model group,and the relative expression of NLRP3 and Caspase-1 protein in hippocampus was significantly increased(P<0.05).Compared with model group,neuron damage in hippocampus of NaHS group was reduced,and serum H₃S content was significantly increased(all P<0.05),NLRP3 and Caspase-1 proteins in hippocampus were significantly decreased(all P<0.05);Compared with model group,neuron damage in hippocampus of CY-09 group was reduced,NLRP3 and Caspase-1 proteins in the hippocampus were significantly decreased,and serum IL-1βand IL-18 levels were significantly decreased(all P<0.05);Conclusions IRI could increase NLRP3 expression in VaD rats.H₃S could reduce IRI in rats by decreasing NLRP3 expression.