核苷酸结合寡聚化结构域样受体蛋白3炎症小体及其抑制剂MCC950在高盐所致高血压大鼠心肌重塑中的研究  

Study of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and its inhibitor MCC950 in myocardial remodeling of hypertensive rats induced by high salt

作　　者：秦汉 于凤侠[2] 陈昌毅 林树无[2] QIN Han;YU Fengxia;CHEN Changyi;LIN Shuwu(Department of Cardiology,the Second Affiliated Hospital of Shenyang Medical College,Liaoning,Shenyang,110002,China;Department of Cadre Ward,the Second Affiliated Hospital of Shenyang Medical College,Liaoning,Shenyang,110002,China;Department of General Practice,Affiliated Minda Hospital of Hubei University for Nationalities,Enshi,Hubei,445000,China)

机构地区：[1]沈阳医学院附属第二医院心内科,辽宁沈阳110002 [2]沈阳医学院附属第二医院干诊病房,辽宁沈阳110002 [3]湖北民族大学附属民大医院全科病房,湖北恩施445000

出　　处：《当代医学》2024年第34期1-7,共7页Contemporary Medicine

基　　金：沈阳市科技计划项目(20-205-4-082)。

摘　　要：目的研究高盐所致高血压发生机制中核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎症小体的作用,并通过NLRP3炎症小体抑制剂(MCC950)靶向治疗,以延缓高血压进展及改善高血压所致的心肌纤维化。方法选取3周龄健康雄性Wistar大鼠24只,体质量35~45 g,按照随机数字表法分为实验组、干预组及对照组,每组8只。实验组、干预组给予8%氯化钠颗粒饲料喂养,对照组给予0.5%氯化钠颗粒饲料喂养,共喂养18周;鼠尾血压(收缩压)>140 mmHg(1 mmHg=0.133 kPa)为建模成功,17周起干预组鼠尾静脉注射MCC950,实验组、对照组腹腔注射0.9%氯化钠溶液。测量并比较不同周龄大鼠收缩压;采用苏木精-伊红染色(hematoxylin-eosin staining,HE)法、Masson法检测心肌炎症细胞浸润、纤维化程度及间质增生情况,使用NIS.elementBr 4.0软件进行图像分析;采用免疫组织化学法检测大鼠心肌中NLRP3炎症小体和白细胞介素(interleukin,IL)-1β、IL-18抗体表达,实时荧光定量PCR检测大鼠心肌中NLRP3炎症小体和IL-1β、IL-18的mRNA表达量。结果3、5周龄,3组收缩压比较差异无统计学意义;7、11、15、19、21周龄,3组收缩压比较差异有统计学意义(P<0.05),且实验组、干预组收缩压均高于对照组,而干预组7、21周龄收缩压均低于实验组,差异有统计学意义(P<0.05),实验组与干预组其他时间点收缩压比较差异无统计学意义。HE、Masson染色结果显示,实验组、干预组较对照组心肌细胞明显肿胀,毛细血管间质增生,伴血管周细胞肿胀、间质胶原沉积,但干预组轻于实验组。实验组、干预组炎症细胞浸润情况均重于对照组,但干预组轻于实验组,差异有统计学意义(P<0.05)。实验组、干预组大鼠心肌纤维化程度及间质增生均重于对照组,但干预组轻于实验组,差异有统计学意义(P<0.05)。实验组、干预组大鼠心肌�Objective To study the role of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome in the pathogenesis of high salt-induced hypertension,and NLRP3 inflammasome inhibitor(MCC950)targeted therapy was used to delay the progression of hypertension and improve myocardial fibrosis caused by hypertension.Methods 243-week-old healthy male Wistar rats with a body weight of 35-45 g were selected,and they were divided into the experimental group,the intervention group and the control group according to random number table method,with 8 rats in each group.The experimental group and intervention group were fed with 8%sodium chloride pellet feed,and the control group were fed with 0.5%sodium chloride pellet feed,for a total of 18 weeks.Rat tail blood pressure(systolic blood pressure)>140 mmHg(1 mmHg=0.133 kPa)was considered to be successful in modeling,since 17 weeks,the rats in the intervention group were injected with MCC950,and the ex‐perimental group and control group were injected with 0.9%sodium chloride solution intraperitoneally.Systolic blood pressure was measured and compared in rats of different weeks of age;hematoxylin-eosin staining(HE)and Masson methods were used to detect myocardial inflammatory cell infiltration,fibrosis degree and interstital proliferation,and image analysis was conducted using NIS.elementBr 4.0 software,the expression of NLRP3 inflammasome,interleukin(IL)-1βand IL-18 antibody in rat myocardium was detected by immunohistochemical method,and the mRNA ex‐pression of NLRP3 inflammasome,IL-1βand IL-18 in rat myocardium was detected by real-time fluorescent quantitative PCR.Results At 3 and 5 weeks of age,there were no significant differences in systolic blood pressure among the three groups;at 7,11,15,19 and 21 weeks of age,there were significant differences in systolic blood pressure among the three groups(P<0.05),and the systolic blood pressure in the experimental group and the intervention group were higher than that in the control group,while the systolic

关 键 词：MCC950 核苷酸结合寡聚化结构域样受体蛋白3炎症小体 白细胞介素-1Β 白细胞介素-18 

分 类 号：R47[医药卫生—护理学]