蛋白酶体抑制剂对糖尿病肾病大鼠的治疗作用.docVIP

· 910 · 医学研究生学报2010年9月第23卷第9期J Med Postgra,Vol. 23,No. 9,September,2010 论 著 (基础研究) 蛋白酶体抑制剂对糖尿病肾病大鼠的治疗作用 齐 伟，牟 娇，郭艳红，曾 薇，罗志锋，冯 兵 [摘要] 目的 糖尿病肾病(diabetic nephropathy,DN)是一种高糖刺激的炎症性疾病，泛素蛋白酶体是调节炎症细胞因 子关键转录因子NF-kB 的上游信号系统，拟探讨蛋白酶体抑制剂MC-132 对大鼠 DN 的治疗作用。 方法 54 只成年SD 雄 性大鼠随机分为正常对照(normal control,NC)组、糖尿病肾病模型(diabetic nephropathy,DN)组、MG-132 治疗组。分别在药 物干预的4、8、12周时测定大鼠体重(body weight,BW)、肾重(kidney weight,KW)及体重/肾重指数( kidney weight/body weight index,KI)、血糖(glucose,Glu)、三酰甘油(triglycerides,TG)、总胆固醇(total cholesterol,TC)、24h 尿蛋白排泄率(urinary albumin excretion rate,UAER),同时观察肾脏病理学改变。 结果 ①与 NC组比较，DN 大鼠的Glu、TG、TC、24 h UAER 均明显升高 (P0.05)。MG-132 治疗可显著降低大鼠的Glu水平、显著减少24hUAER(P0.05),TG、TC 也显著降低(P0.05)。② 与 NC 组大鼠比较，DN 组大鼠KW 明显增加，KI显著增大(P0.05)。MG-132 治疗后KI 明显下降(P0.05)。③MG-132 治疗 DN 大鼠的肾脏病理表现，如肾小球基底膜增厚，系膜细胞增生、系膜基质积聚，得以减轻。系膜细胞和肾小管上皮细胞表达α 平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)明显减少。 结论 泛素蛋白酶体途径(ubiquitin proteasome pathway,UPP) 可能是治疗 DN 的有效药物靶点。 [关键词] 蛋白酶体抑制剂；糖尿病肾病；炎症反应；内质网应激 [中图分类号] R587.2 [文献标志码] A [文章编号] 1008-8199(2010)09-0910-05 Effect of proteasome inhibitor on diabetic nephropathy in rats QI Wei, MU Jiao, GUO Yan-hong, ZENG Wei, LUO Zhi-feng, FENG Bing (Department of Nephrology,Xingiao Hospital, Third Military Medical University, Chongqing Institute of Kidney Dis- ease 400037,Chongqing,China) [Abstract ] Objective It is well-known that diabetic nephropathy is an sub-inflammatory diseasse, which is stimulated by high-glu- cose. Ubiquitin-proteasome system plays an important role on regulating the upstream of transcription factor NF-kB signaling system. There- fore, this study was to investigate the effect of proteasome inhibitor MG132 on diabetic nephropathy in rats. Methods Fifty-four male SD rats were randomly divided into three groups, which were normal control group(NC),diabetic nephropathy group(DN)and diabetic nephropa- thy treated with MG- 132 group(MG132). At the end of 4, 8 and 12 weeks, body weigh