CAJ | 학술논문

目的研究丝裂原活化蛋白激酶38(p38MAPK)在链脲左菌素(STZ)诱导的糖尿病小鼠肾组织中的表达及活化情况,从分子信号角度探讨糖尿病肾病肾纤维化的发病机制.方法采用STZ腹腔注射诱导小鼠糖尿病模型,并检测血糖、血肌酐、24 h尿白蛋白排泄率、肾小球细胞外基质;用免疫组织化学方法检测糖尿病小鼠肾组织磷酸化p38MAPK和TGFβ的表达,用RT-PCR的方法检测肾组织p38MAPK和TGFβmRNA的表达.结果腹腔注射STZ后,模型组小鼠均出现明显的多食、多饮、多尿和体质量下降等糖尿病症状,血糖明显升高,血肌酐水平明显增高,24 h尿白蛋白排泄率明显增加,肾小球细胞外基质明显增宽.正常肾组织有基础的磷酸化p38MAPK和p38MAPKmRNA表达,糖尿病形成后4周,磷酸化p38MAPK和p38MAPK mRNA在肾组织中的表达明显增高,并持续增加到8周,第12周至16周磷酸化p38MAPK和p38MAPK mRNA的表达有所减少.正常肾组织有基础的TGFβ1蛋白和mRNA表达.糖尿病形成后4周,TGFβ1蛋白和mRNA在肾组织中的表达均明显增高,并持续增加到12周,第16周肾组织TGFβ1的表达有所减少.肾组织磷酸化p38MAPK和TGFβ1的表达趋势一致,并呈明显正相关(r=0.64,P＜0.01),且与肾小球细胞外基质的积聚密切相关.结论 p38MAPK的表达和活化可能通过介导TGFβ1的表达参与了小鼠糖尿病肾病模型肾纤维化的发生.
목적 연구사렬원활화단백격매38(p38MAPK)재련뇨좌균소(STZ)유도적당뇨병소서신조직중적표체급활화정황,종분자신호각도탐토당뇨병신병신섬유화적발병궤제.방법 채용STZ복강주사유도소서당뇨병모형,병검측혈당、혈기항、24 h뇨백단백배설솔、신소구세포외기질;용면역조직화학방법검측당뇨병소서신조직린산화p38MAPK화TGFβ적표체,용RT-PCR적방법검측신조직p38MAPK화TGFβmRNA적표체.결과 복강주사STZ후,모형조소서균출현명현적다식、다음、다뇨화체질량하강등당뇨병증상,혈당명현승고,혈기항수평명현증고,24 h뇨백단백배설솔명현증가,신소구세포외기질명현증관.정상신조직유기출적린산화p38MAPK화p38MAPKmRNA표체,당뇨병형성후4주,린산화p38MAPK화p38MAPK mRNA재신조직중적표체명현증고,병지속증가도8주,제12주지16주린산화p38MAPK화p38MAPK mRNA적표체유소감소.정상신조직유기출적TGFβ1단백화mRNA표체.당뇨병형성후4주,TGFβ1단백화mRNA재신조직중적표체균명현증고,병지속증가도12주,제16주신조직TGFβ1적표체유소감소.신조직린산화p38MAPK화TGFβ1적표체추세일치,병정명현정상관(r=0.64,P＜0.01),차여신소구세포외기질적적취밀절상관.결론 p38MAPK적표체화활화가능통과개도TGFβ1적표체삼여료소서당뇨병신병모형신섬유화적발생.
Objective To investigate the expression of p38 mitogen actirated protein kinase (p38MAPK) in renal fibrosis in diabetic mice. Methods Male homozygous C57 BL/6 mice were divided at random into control group intraperitoneally(i. p.) injected with citrate buffer and diabetes group received 5 consecutive daily intraperitoneal inserum glucose level exceeding 16.7 mmol/L. Mice were killed at 0,4weeks ,8weeks, 12weeks and 16weeks respectively after STZ injected. The kidney tissues were obtained from diabetic and control mice. Serum glucose, extracellular matrix,and 24 h urinary albumin excretion rate(UAE)and the serum creatinine(Scr) were measured. The kidney tissue was used for histological and morphometric studies of glomerular matrix expansion (PAS), and the expression of phosphorylated p38MAPK and TGFβ1 were measured by immunohisteehemical staining. p38MAPK and TGFβ1mRNA were analyzed by reverse transeriptase-PCR. Results The serum level of glucose in diabetic mice increased significantly. Scr and 24 h UAE, and glomerular matrix expansion in diabetic mice were obviously higher than that in control mice. Phosphorylated p38MAPK and TGFβ1 levels were obviously increased in the kidney of diabetic mice compared with those in control mice(P ＜0. 01) ;TGFβ1 expression was positively related to the expression of phosphorylated p38MAPK. Conclusion The overexpression of phosphorylated p38MAPK in kidney shoud play an important role in the development of renal fibrosis associated with diabetic nephropathy in mice.