【摘要】 目的 探讨益肾十七味丸对阿霉素诱导肾病模型小鼠焦孔素E（GSDME）、胱天蛋白酶3（caspase 3）表达的影响，及其保护机制。方法 将50只BALB/c小鼠按照随机分组法分为正常组、模型组和低、中、高剂量实验组，每组10只。模型组和低、中、高剂量实验组采取尾静脉注射方式一次性注射10.5 mg·kg^-1阿霉素，同时低、中、高剂量实验组分别灌胃给予150、240、330 mg·kg^-1·d^-1益肾十七味丸；正常组和模型组均灌胃给予等体积0.9%NaCl。5组小鼠均持续给药28 d。用酶联免疫吸附试验法检测血清白蛋白（ALB）及血清肌酸酐（SCr）水平，用免疫组织化学染色法检测GSDME介导的细胞焦亡通路关键分子的表达特征，用蛋白质印迹法检测GSDME和caspase 3蛋白的表达水平。结果 中、高剂量实验组和模型组、正常组的血清ALB分别为（23.31±2.80）、（24.95±1.55）、（17.44±2.25）和（30.49±2.27）mg·mL^-1,SCr分别为（27.16±1.37）、（25.52±1.20）、（34.41±2.12）和（23.04±2.78）μmol·L^-1,caspase 3蛋白相对表达水平分别为0.81±0.17、0.47±0.21、1.25±0.14和0.43±0.11,caspase 3活化形式（caspase 3 17 kDa）蛋白相对表达水平分别为0.60±0.33、0.41±0.19、0.97±0.02和0.43±0.13,GSDME蛋白相对表达水平分别为0.69±0.11、0.39±0.07、1.17±0.12和0.41±0.03,N末端片段裂解形成焦孔素E氮端（GSDME-N）蛋白相对表达水平分别为0.82±0.17、0.41±0.05、1.30±0.02和0.76±0.11。中、高剂量实验组的上述指标与模型组比较，差异均有统计学意义（P<0.01,P<0.05）。结论 益肾十七味丸通过调控caspase 3-GSDME焦亡通路，从而改善阿霉素肾病。更多还原

【Abstract】 Objective To investigate the effect of Yishen shiqiwei pills on the expression of gasdermin E（GSDME） and caspase 3 in adriamycin induced nephropathy model mice and their protective mechanism.Methods Fifty BALB/c mice were randomly divided into normal group,model group,experimental-L,-M and-H groups.Model and experimental-L,-M,-H groups were given a one-off tail vein injection of adriamycin 10.5 mg·kg^-1.At the same time,experimental-L,-M,-H groups were given 150,240,330 mg·kg^-1·d^-1Yishen shiqiwei pills by gavage;normal and model groups were given the same volume 0.9%NaCl by gavage.Five groups were were treated for 28d.Blood,urine and kidney tissues were taken after 28 days.Enzymelinked immunosorbent assay was used to detect serum albumin （ALB） and serum creatinine （SCr）.The expression characteristics of key molecules in the GSDME-mediated cell apoptosis pathway were detected by immunohistochemistry.The expression levels of GSDME and caspase 3 proteins were detected by Western Blot.ResultsThe serum ALB levels of the middle and high dose experimental groups,model groups and normal groups were（23.31±2.80）,（24.95±1.55）,（17.44±2.25） and （30.49±2.27） mg·m L^-1,the SCr levels were（27.16±1.37）,（25.52±1.20）,（34.41±2.12） and （23.04±2.78）μmol·L^-1;the relative expression levels of caspase 3 protein were 0.81±0.17,0.47±0.21,1.25±0.14 and 0.43±0.11;the relative expression levels of caspase 3 activated form （caspase 3-17 k Da） protein were 0.60±0.33,0.41±0.19,0.97±0.02 and0.43±0.13;the relative expression levels of GSDME protein were 0.69±0.11,0.39±0.07,1.17±0.12 and0.41±0.03;the relative expression levels of gasdermin E-N （GSDME-N） protein were 0.82±0.17,0.41±0.05,1.30±0.02 and 0.76±0.11,respectively.Compared with the model group,the differences of above indexes in the experimental-M and experimental-H were statistically significant （P<0.01,P<0.05）.ConclusionYishen shiqiwei pills can improve adriamycin nephropathy by regulating caspase 3-GSDME focal death pathway.更多还原