CAJ | 학술논문

目的了解原发性痛风(PG)患者的半胱氨酸天冬氨酸特异性蛋白酶-1(CASP1)基因及各转录剪接体mRNA表达水平及作用.方法用半定量RT-PCR法检测96例PG患者和96名健康体检者(HC) PBMCs中CASP1基因及各转录剪接体mRNA表达水平.用蛋白印迹法检测PG患者和HCPBMCs中CASP1、NF-κB(p105/p50)蛋白表达水平.对各观察组间的mRNA表达水平采用Wilcoxon秩和检验,蛋白表达水平采用t检验.结果 PG组CASP1基因mRNA表达量显著高于健康体检组[0.199 7(0.634 5)和1.151 7(1.969 6),Z=-6.454,P=0.000],PG组CASP1基因转录剪接体6、7 mRNA表达量显著低于HC组[分别为4.448 7(5.029 6)和3.020 9(2.877 3)、4.930 1(4.8861)和3.456 4(2.655 6),Z均=-3.735,P均=0.000],CASP1基因转录剪接体α、β、γ、x mRNA表达在PG组与HC组差异无统计学意义[分别为2.083 1(4.404 5)和2.043 1(2.688 2)、2.249 5(3.328 0)和2.082 6(3.119 9)、2.911 3(4.287 1)和2.789 8(2.538 2)、2.413 5(4.712 4)和2.511 3(2.429 0),P均＞0.05];PG组CASP1蛋白表达显著低于HC组(64.82±10.76和0.78±0.24,t=76.379,P＜0.01),PG组NF-κB (p105/p50)蛋白表达显著高于HC组(0.127±0.008和0.263±0.106,t=-26.322,P＜0.01).结论 CASP1基因及各转录剪接体mRNA在PG患者中表达异常,提示在PG患者的炎症反应中CASP1基因及各转录剪接体可能发挥重要的介导作用;PG患者CASP1蛋白表达水平与CASP1基因部分转录剪接体mRNA表达趋势一致,提示若对CASP1部分基因转录剪接体进行有效的药物干预可能对PG患者的治疗起到一定的作用.
목적 료해원발성통풍(PG)환자적반광안산천동안산특이성단백매-1(CASP1)기인급각전록전접체mRNA표체수평급작용.방법 용반정량RT-PCR법검측96례PG환자화96명건강체검자(HC) PBMCs중CASP1기인급각전록전접체mRNA표체수평.용단백인적법검측PG환자화HCPBMCs중CASP1、NF-κB(p105/p50)단백표체수평.대각관찰조간적mRNA표체수평채용Wilcoxon질화검험,단백표체수평채용t검험.결과 PG조CASP1기인mRNA표체량현저고우건강체검조[0.199 7(0.634 5)화1.151 7(1.969 6),Z=-6.454,P=0.000],PG조CASP1기인전록전접체6、7 mRNA표체량현저저우HC조[분별위4.448 7(5.029 6)화3.020 9(2.877 3)、4.930 1(4.8861)화3.456 4(2.655 6),Z균=-3.735,P균=0.000],CASP1기인전록전접체α、β、γ、x mRNA표체재PG조여HC조차이무통계학의의[분별위2.083 1(4.404 5)화2.043 1(2.688 2)、2.249 5(3.328 0)화2.082 6(3.119 9)、2.911 3(4.287 1)화2.789 8(2.538 2)、2.413 5(4.712 4)화2.511 3(2.429 0),P균＞0.05];PG조CASP1단백표체현저저우HC조(64.82±10.76화0.78±0.24,t=76.379,P＜0.01),PG조NF-κB (p105/p50)단백표체현저고우HC조(0.127±0.008화0.263±0.106,t=-26.322,P＜0.01).결론 CASP1기인급각전록전접체mRNA재PG환자중표체이상,제시재PG환자적염증반응중CASP1기인급각전록전접체가능발휘중요적개도작용;PG환자CASP1단백표체수평여CASP1기인부분전록전접체mRNA표체추세일치,제시약대CASP1부분기인전록전접체진행유효적약물간예가능대PG환자적치료기도일정적작용.
Objective To study the expression level and role of cystein aspartate specific procease-1 (CASP1)gene transcript variant mRNA in patients with primary gout (PG).Methods CASP1 gene transcript variant mRNA was measured using reverse transcription-polymerase chain reaction (RT-PCR) in peripheral blood monocytes (PBMCs).The expression of CASP1 gene transcript variant mRNA in PBMCs was compared between patients with PG (n=96) and healthy controls (n=96).CASP1 and NF-κB (p105/p50) protein expression was measured using Western blot in PBMCs,β-actin was selected as the internal control.Wilcoxon rank sum test of two independent samples was used to compare the expression of CASP1 gene transcript variant mRNA in PBMCs Students' t-test in two independent samples was used to compare the protein expression.Results The expression of CASP1 gene mRNA was increased significantly in patients with PG compared to healthy controls [0.199 7 (0.634 5) vs 1.151 7 (1.969 6),Z=-6.454,P=0.000],and the expression of CASP1 gene transcript variant 6,7 mRNA in PG was significantly lower when compared to healthy controls [4.448 7(5.029 6) vs 3.020 9(2.877 3),4.930 1(4.886 1) vs 3.456 4(2.655 6),Z=-3.735,P=0.000].The expression of CASP1 gene transcript variant alpha,beta,gamma,x mRNA in PG was not different when compared to healthy controls [2.083 1 (4.404 5) vs 2.043 1 (2.688 2),2.249 5(3.328 0) vs 2.082 6(3.119 9),2.911 3(4.287 1) vs 2.789 8(2.538 2),2.413 5(4.712 4) vs 2.511 3(2.429 0),P＞0.05].The expression of CASP1 protein in PG was significantly lower when compared to healthy controls (64.82± 10.76 vs 0.78±0.24,t=76.379,P＜0.01),and the expression of NF-κB (p105/p50) protein was increased significantly in patients with PG compared to healthy controls (0.127±0.008 vs 0.263±0.106,t=-26.322,P＜ 0.01).Conclusion Dysregulated expression of the CASP1 gene transcript variant is involved in the inflammatory response and plays a key role in the pathogenesis of PG.The expression of CASP1 protein is consistent with that of the CASP1 part gene transcript variant of PG,suggests that these genes might be a potential targets for the treatment of patients with PG.