TGF-β／Smad阻遏子c-Ski与糖尿病肾病的相关性研究  

The correlation research of TGF-β/Smad signal pathway repressor c-Ski and diabetic nephropathy

作　　者：田雪 张捷[2] 于倩 刘德敏 

机构地区：[1]安徽省马鞍山市临床检验中心, 安徽省243000 [2]天津医科大学代谢病医院卫生部激素与发育重点实验室,天津市300070

出　　处：《实用检验医师杂志》2013年第2期79-83,共5页Chinese Journal of Clinical Pathologist

基　　金：基金项目：天津市卫生局科技基金资助课题（09KY24）

摘　　要：目的探讨阻遏子c—Ski对TGF-β／Smad信号途径的抑制作用与糖尿病肾病（diabetic nephropathy，DN）的关系。方法将所有大鼠随机分为正常对照组（NC组）、糖尿病（diabetes mellitus，DM）模型组（DM组）和吡格列酮干预组（PT组）。尾静脉小剂量注射链脲佐菌素建立DM大鼠模型。在实验期间连续监测血糖，8w末处死动物并采集血尿标本用于相关的生化指标测定，采用real—timePCR方法检测TGF-β和c—Ski的mRNA水平，免疫组化法检测TGF—β1和c—Ski蛋白表达情况，并进行统计学分析。结果与NC组相比，DM组血糖和血尿素氮（blood urea nitrogen，BUN）、24h尿微量白蛋白（24 hours urinary microalbumin，24hUMA）水平明显升高，经PT干预后大鼠血糖、BUN、24hUMA水平较DM组均显著下降，差异均有统计学意义（P均〈0．05）。PCR结果显示，DM组的TGF-β1mRNA水平较NC组显著升高，经PT干预后，其表达量显著降低，差异均有统计学意义（P均〈0．05），而c—SkimRNA水平三组间差异无统计学意义（P〉0．05）。与NC组比较，DM组肾组织病理形态呈阳性表达，而PT组与NC组相近。免疫组化结果显示TGF-β1表达量在DM组较NC组显著增加，但c—Ski蛋白表达低于NC组，经盯干预后TGF-β1表达较DM组下降，而c—Ski表达显著增加，差异均有统计学意义（P均〈0．05）。结论DN中阻遏子c—Ski表达的下调减少了对TGF-β／Smad途径的阻断作用，而PPAR-γ可减少这种下调，为DN治疗机制的研究提供新的实验依据。Objective To investigate the negative regulatory mechanism of c-Ski to TGF-β/Smad signal pathway in patients with diabetic nephropathy（DN）. Methods Rats were randomized into normal control group （NC group）, diabetes group （DM group） and pioglitazone group （PT group）. Murine diabetic models were induced with streptozotoein. All the indicators related to renal function such as blood urea nitrogen（BUN） and 24 hours urinary mieroalbumin （24 hUMA） were detected in rats sacrificed after 8 weeks of experiment. The mRNA expression levels of c-Ski and TGF-β1 were detected by real-time PCR, and the protein expression of TGF-β1 and c-Ski were determined by immunohistoehemistry and statistically analyzed. Results Compared with NC group, the levels of BUN, 24 hUMA and blood sugar were higher in DM group, and the levels were decreased after treated by PT, and the differences all had statistical significance （Pall〈 0.05 ）. The results of PCR showed that the level of TGF-β1mRNA in DM group was higher than in NC group, after treated by PT, the level of TGF-β1mRNA decreased significantly than in DM group, and the differences all had statistical significance （Pall〈 0.05）. There were no statistical significance in c-Ski mRNA levels among three groups （P〉 0.05 ）. Compared with NC group, the modality of kidney tissue shown positive expression in DM group, but little change in PT group. The results of immunohistochemisty showed that the levels of TGF-β1 in DM group were higher, but c-Ski were lower than in NC group, while after treated by PT, the levels of TGF- γ1 expressed lower, but c-Ski expressed higher than in DM group, and the differences all had statistical significance （Pall〈 0.05）. Conclusion PPAR-γcan significantly up-regulate protein level of c-Ski to inhibit TGF-β/Smad pathway in kidney tissue of diabetic rats, which may provide new evidence for DN therapeutic machanism research.

关 键 词：糖尿病 转化生长因子-Β1 糖尿病肾病 c—Ski PPAR-Γ 

分 类 号：R692.202[医药卫生—泌尿科学]