地塞米松抑制肾小球上皮间质转化  

Dexamethasone Inhibits Glomerular Epithelial-mesenchymal Transition

作　　者：邹敏书[1] 余健[1] 聂国明 齐曼丽[2] 李琳[1] 罗莉漫[1] 徐洪涛[1] 

机构地区：[1]广州军区武汉总医院儿科,430070 [2]广州军区武汉总医院病理科,430070

出　　处：《医学研究杂志》2011年第12期77-80,共4页Journal of Medical Research

摘　　要：目的观察地塞米松对阿霉素肾病大鼠肾小球足细胞标志蛋白nephrin、间质转化调节因子ILK、间质标志蛋白α-SMA表达的影响,探讨其减轻蛋白尿的机制。方法 SD大鼠尾静脉1次性注射阿霉素制作肾病模型,24只诱导成功的模型鼠随机分为两组:(1)肾病组(NE组,n=12);(2)肾病+地塞米松治疗组(DE组,n=12),腹腔注射地塞米松0.3mg/kg,每周2次。另以10只SD大鼠作为对照组(NC组,n=10)。第8周测定血清C-反应蛋白(CRP)、降钙素原(PCT)、肌酐(Cr)、半胱氨酸蛋白酶抑制剂C(Cys C)、清蛋白(A);尿液中24h尿白蛋白(24h AU)及尿足细胞(UPC)排泄水平;RT-PCR和Western boltting检测肾小球nephrin、ILK、α-SMA mRNA和蛋白质的表达。结果 NE组CRP、PCT、Cr、Cys C、24h AU较NC组明显升高,A水平较NC组明显降低,两两比较差异均有统计学意义(P<0.01),两组UPC的排泄无明显差异。NE组肾小球nephrin mRNA和蛋白质的表达较NC组明显降低,ILK、α-SMA mRNA和蛋白质的表达较NC组显著升高,两两比较差异均有统计学意义(P<0.01)。地塞米松明显改善ADR肾病鼠CRP、PCT、Cr、Cys C的升高和A的降低;恢复肾小球nephrin mRNA和蛋白质的表达,并抑制ILK、α-SMA mRNA和蛋白质的表达。结论地塞米松可减轻炎症反应;维持nephrin的表达,减轻尿白蛋白的排泄;抑制细胞表型转化的标记因子ILK、α-SMA的表达,抑制EMT。Objective To observe the effects of dexamethasone on the expressions of podocyte marker of nephrin at the slit diaphragm, epithelial - mesenchymal transition （EMT） - related mediator of integrin - linked kinase （ILK） , and mesenchymal marker of α- smooth muscle actin （ α- SMA） in adriamyein - induced nephrotie rats, and investigate the mechanism of ameliorating proteinuria. Methods Twenty - four Sprague - Dawley rats were treated with a single dose of adriamycin via vena eaudalis injection to induce nephropathy model, and randomly divided into nephropathy group （NE, n = 12） and NE ＋ dexamethasone treament group （ DE, n = 12）. Rats in DE group received dexamethasone treatment （0.3mg/kg） through intraperitoneal injection twice a week. Normal SD rats served as control group （NC, n = 10）. At 8 weeks, serum C -reactive protein （CRP） , procalcitonin （PCT） , creatinine （Cr） , cystatin C （Cys C） ,24h albuminuria（24h AU）and urinary podocytes （UPC） were measured. Glomerular nephrin, ILK and α-SMA mRNA and proteins expressions were detected by RT - PCR and Western blotting, respectively. Results The levels of CRP, PCT, Cr, Cys C and 24h AU in NE group were significantly elevated （P 〈 0.01 ）. The A level was markedly reduced, and the excretion of UPC had no significant difference was compared with NC group. Compared with the NC group, the mRNA and protein expressions of nephrin were significantly decreased and ILK, α- SMA were significantly increased in the NE group. Dexamethasone reduced the levels of CRP, PCT, Cr, Cys C and elevated the level of A, recovered the expression of nephrin mRNA and protein, and suppressed expression of ILK and α- SMA mRNA and protein in adriamycin nephropathy. Conclusion Dexamethasone can ameliorate inflammatory response, preserve the expressions of nephrin to mitigate albuminuria, inhibit the expression of marker factors of cell phenotype transformation - ILK and α- SMA to suppress EMT.

关 键 词：地塞米松 EMT NEPHRIN ILK Α-SMA 

分 类 号：R735.34[医药卫生—肿瘤]