摘要
目的观察Toll样受体4（TLR4）在糖尿病大鼠肾脏的表达及全反式维甲酸（ATRA）对肾组织TLR4表达的影响。方法将18只大鼠随机分为对照组（N组）、糖尿病组（DM组）和AT—RA组（T组），每组6只。DM组和T组用链脲佐菌素诱导糖尿病模型。T组给予ATRA20mg·k^-1·d^-1灌胃8周。于第8周末比较各组大鼠24h尿蛋白量、肌酐清除率（Ccr）、肾质量／体质量比值。逆转录聚合酶链反应（RT-PCR）法检测各组大鼠肾组织TLR4 mRNA的表达。免疫组织化学法检测肾组织TLR4蛋白的表达部位和强度。结果①DM组24h尿蛋白量、Ccr、肾质量／体质量比值均高于正常组，T组尿蛋白量和Ccr较DM组明显降低，差异均有统计学意义（P〈0．01）；②DM组TLR4 mRNA表达高于N组，T组TLR4 mRNA表达高于DM组，差异均有统计学意义（P〈0．01）；③TLR4主要表达于近曲、远曲小管上皮细胞和部分肾小球细胞，DM组TLR4表达高于N组，T组TLR4表达高于DM组，差异均有统计学意义（P〈0.01）。结论ATRA可能通过干预肾组织TLR4表达，从而延缓糖尿病肾脏病进展。
Objective To investigate effects of all-trans retinoic acid （ATRA） on renal expression of toll-like receptor 4 （TLR4） in streptozotocin-induced diabetic rats. Methods Eighteen rats were randomly divided into control group （group N）, animal model group （group DM） and therapy group （group T）. Animals in group DM and group T were treated with streptozotocin, and those in group T were administrated with ATRA （20 mg·kg^-1 ·d^-1 ） dissolved with vegetable oil. Twenty-four hour urinary protein, endogenous creatinine clearance rate （Ccr）, and kidney weight/body weight were determined after 8 weeks. Immunohistochemistry and reverse transcription polymerase chain reaction （RT-PCR） were performed to detect the expression of TLR4 protein and mRNA respectively. Results ①Twenty-four hour urinary protein, Ccr and kidney weight/body weight were significantly increased in group DM as compared with group N and group T （P〈0. 01） ;②TLR4 staining was observed in the renal tubular epithelial cells in rat kidneys. In group DM, the protein expression of TLR4 was significantly increased compared to that in group N （P〈0. 01）, and that in group T was significantly increased compared to that in group DM （P〈0. 01）;③ In group DM, the expression of TLR4 mRNA was significantly increased compared to that in group N （P〈0. 01）, and that of TLR4 in group T was significantly higher than in group DM （P〈0. 01）. Conclusions ATRA exhibits a protecting role in the pathogenesis of diabetic nephropathy by increasing TLR4 expression in renal tissues.
出处
《临床肾脏病杂志》
2009年第8期367-369,F0003,共4页
Journal Of Clinical Nephrology
