p53、p21及半胱氨酸天冬氨酸蛋白酶3蛋白在川崎病小鼠冠状动脉病变中的诊断价值

Value of p53,p21,and Caspase-3 in diagnosis of coronary artery lesion in mice with Kawasaki disease

目的探讨p53、p21及半胱氨酸天冬氨酸蛋白酶3(Caspase-3)蛋白在川崎病(KD)小鼠冠状动脉病变(CAL)中的诊断价值,为临床诊治奠定理论基础。方法采用干酪乳杆菌细胞壁提取物制备KD小鼠CAL模型。采用免疫组化方法检测两组小鼠(健康对照组和KD组)冠状动脉根部p53、p21和Caspase-3蛋白水平。绘制受试者工作特征曲线(ROC),测定曲线下面积(AUC)、95%可信区间区(95%CI)、p53、p21和Caspase-3表达,预测KD小鼠冠状动脉平滑肌细胞(CASMCs)凋亡和CAL形成能力的灵敏度、特异度和截断值。结果与正常小鼠相比,KD小鼠凋亡指数明显升高,p53、p21和Caspase-3表达上调。Caspase-3的免疫反应评分(IRS)与p53和p21的IRSs呈正相关。预测CAL存在的p53、p21和Caspase-3表达的最佳截断值分别为4.15、4.18和4.22。结论p53和p21表达的上调,通过激活Caspase-3可促进KD小鼠CASMCs的凋亡。p53、p21和Caspase-3可能是KD小鼠CAL形成及CASMCs凋亡的有效预测因子。

Objective To explore the value of p53,p21,and Caspase-3 in diagnosis of coronary artery lesion(CAL)in mice with Kawasaki disease(KD),provide a theoretical basis for clinical diagnosis and treatment.Methods The KD mouse model with CAL was established by administration of Lactobacillus casei cell wall extract.In the two groups(healthy control group and KD group),the protein levels of p53,p21,and Caspase-3 in the root of coronary artery were detected by immunohistochemistry.Receiver operating characteristic curve(ROC)was drawn to detect the area under the curve(AUC),95%confidence interval(CI),the expressions of p53,p21,and Caspase-3,the sensitivity,specificity,and cut-off value of the ability of CASMCs apoptosis and CAL formation in KD mice were predicted.Results Compared with healthy mice,apoptosis index in KD mice increased significantly,the expressions of p53,p21,and Caspase-3 were upregulated.The immunoreactive score(IRS)of Caspase-3 was positively correlated with IRSs of p53 and p21.The optimal cutoff values of p53,p21,and Caspase-3 expressions for predicting the presence of CAL were 4.15,4.18,and 4.22,respectively.Conclusion Upregulated expressions of p53 and p21 followed by Caspase-3 activation promote apoptosis of CASMCs in KD mice.p53,p21,and Caspase-3 may be the effective predictive factors for CAL formation and CASMCs apoptosis in KD mice.