NF-κB/NLRP3通路对动脉粥样硬化小鼠脂质沉积及自噬相关蛋白表达的影响  

Effect of nuclear transcription factor kappa B/NOD-like receptor family pyrin domain containing protein 3 pathway on lipid deposition and autophagy related protein expressions in aortic atherosclerosis mice

作　　者：朱康宁[1] 郭凤霞 高岚[1] Zhu Kangning;Guo Fengxia;Gao Lan(Department of Clinical Laboratory,Henan Provincial People's Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院检验科,郑州450003

出　　处：《中华神经医学杂志》2022年第6期580-586,共7页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金(82002199)。

摘　　要：目的探讨核转录因子-κB(NF-κB)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)通路对动脉粥样硬化(AS)模型小鼠脂质沉积及自噬相关蛋白表达的影响。方法以10只6周龄雄性C57BL/6小鼠为对照组,并将20只同龄雄性载脂蛋白E基因敲除(ApoE-/-)小鼠按随机数字表法分为AS组与硼替佐米(BTZ)组,每组10只。予AS组和BTZ组小鼠高脂饮食喂养8周后,BTZ组小鼠给予50μg/kg BTZ腹腔注射(2次/周,持续4周),AS组小鼠注射等量生理盐水。实验过程中持续观察各组小鼠的一般情况,于干预12周后测量其体质量及检测血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)含量,并予HE染色和油红O染色观察小鼠主动脉根部组织病理形态及脂质沉积状况,予免疫组化染色检测小鼠主动脉根部组织中NF-κB、NLRP3的阳性表达,予Western blotting实验检测小鼠主动脉根部组织中自噬相关蛋白Beclin-1、P62和Atg12蛋白的表达量。结果干预12周后,AS组和BTZ组小鼠的体质量,TC、LDL含量,病变程度及脂质沉积占比,NF-κB、NLRP3阳性表达及P62蛋白表达量均明显高于对照组,而BTZ组小鼠这些指标均明显低于AS组,差异均有统计学意义(P<0.05);AS组和BTZ组小鼠的HDL含量、Beclin-1和Atg12蛋白表达量均明显低于对照组,而BTZ组小鼠这些指标均明显高于AS组,差异均有统计学意义(P<0.05)。结论抑制NF-κB/NLRP3通路可通过调节血脂含量以减少脂质沉积,并介导自噬相关蛋白表达以促进自噬发生,从而起到抑制AS进程的作用。Objective To investigate the effect of nuclear transcription factor kappa B(NF-κB)/NOD-like receptor family pyrin domain containing protein 3(NLRP3)pathway on lipid deposition and autophagy related protein expressions in aortic atherosclerosis mice.Methods Ten 6-week-old male C57BL/6 mice were used as control group,and 20 male apolipoprotein E gene knockout(ApoE-/-)mice at the same age were randomly divided into AS group and bortezomib(BTZ)group(n=10).Mice in the AS group and BTZ group were fed with high-fat diet for 8 weeks;and then,mice in the BTZ group were injected intraperitoneally with 50µg/kg BTZ(twice a week,for 4 weeks),while mice in the AS group were injected with same amount of saline.The general states of mice in each group were observed during the experiment process.Twelve weeks after intervention,the body weight and the levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)were measured;the pathological morphology and lipid deposition of plaques at the aortic roots were observed by oil red O staining and HE staining;the expressions of NF-κB and NLRP3 were detected by immunohistochemistry;the expressions of Beclin-1,P62,and Atg12 were measured by Western blotting.Results After 12 weeks of intervention,the body weight,contents of TC and LDL,pathological degrees,proportion of lipid deposition,positive expressions of NF-κB and NLRP3,and P62 protein expression in the AS group and BTZ group were significantly higher than those in the control group,while these indexes in the BTZ group were significantly lower than those in the AS group(P<0.05);HDL content,protein expression levels of Beclin-1 and Atg12 in the AS group and BTZ group was significantly lower than that in the control group,while these indexes in the BTZ group were significantly higher than those in the AS group(P<0.05).Conclusion Inhibition of NF-κB/NLRP3 pathway can reduce lipid deposition by regulating lipid content and mediate the autophagy related protein expressions to promote

关 键 词：动脉粥样硬化 核转录因子-ΚB 核苷酸结合寡聚化结构域样受体蛋白3 自噬 脂质沉积 

分 类 号：R543.5[医药卫生—心血管疾病] R-332[医药卫生—内科学]