摘要
目的:探讨中性调宁蛋白(calponin h2,CN2)在糖尿病肾损害过程中的作用。方法:分别给予中性调宁蛋白转基因(CN2-Tg)小鼠与野生性(WT)C57BL/6J小鼠腹腔注射链脲佐菌素(STZ)制备糖尿病模型,观察两组糖尿病小鼠在注射STZ前及后第8、30天的体重、血糖、血压、尿白蛋白、尿肌酐(Cr)、尿8羟基脱氧鸟苷(8-OHdG)变化及肾组织α-SMA、Ki-67、F4/80免疫组化染色评价肾间质炎症改善情况。结果:CN2-Tg组尿8-OHdG/Cr(ng/mg)明显低于WT组(P<0.05);在第8天CN2-Tg组肾间质细胞纤维化(Ki-67染色)受到明显抑制(P<0.05),第30天不明显(P>0.05);CN2-Tg组肾间质巨噬细胞浸润表现(F4/80染色)在第8(P<0.05)、30天(P<0.01)均受到明显抑制;两组间肾组织α-SMA表达和血压变化无区别。结论:CN2过表达能抑制糖尿病早期肾间质细胞增殖和巨噬细胞浸润,表明CN2可能在糖尿病肾病间质损害的过程中扮演着重要的角色,推断其可能成为治疗糖尿病肾病的新靶点。
Objective : To study the role of neutral ealponin ( ealponin-h2, CN2 ) in the course of diabetic interstitial injury. Methodology:Diabetes was induced by streptozocin (100 mg/kg BW) on both CN2-Tg C57BL/6J mice and wild type ones (WT). The body weight, blood pressure, blood glucose, levels of 24 hour urinary 8-hydroxy- 2'deoxyguanosine (8-OHdG) , ereatinine(Cr) and albumin, and nephreetomy were done on 8 and 30 days after disease induction as well as on day 0. The immunohistochemieal stains for proliferating cells (ki-67), macrophages (F4/80) and phenotypie change of interstitial cells (a-smooth muscle acfin, α-SMA ) for evaluation of interstitial inflammation on all mice and all data were evaluated by computer-analysis system. Results:CN2-Tg diabetic mice showed significantly lower excretion of 24 hour urinary 8-OHdG/Cr(ng/mg) than WT diabetic mice at day 8( 1.03 ±0. 07 in CN2-Tg vs. 1.56 ±0. 15 in WT,P 〈 0.05). The interstitial cell proliferation (ki-67^ + cells/high power field, hpf) was significantly suppressed in CN2-Tg at day 8 ( 3.75 ± 0. 51 vs. 5.70 ± 0. 42, P 〈 0. 05 ), but not at day 30 ( 1.14± 0. 44 vs. 1.23± 0. 24, P 〈 0. 05 ). Reduction of macrophages recruitment in the interstitium ( F4/80 + eells/bpf) was induced in CN2-Tg at clay 8 ( 3. 69± 0. 14 vs. 6. 87 ± 1.33 ,P 〈0. 05) , and day 30 (2. 19 ±0. 70 vs. 5.37 ±0. 48 ,P 〈0. 01 ). There were no significant differences in both α-SMA expression and blood pressure (both systolic and diastolic) between two groups. Conclusion:CN2 overexpression suppressed both of interstitial cell proliferation and maerophages infiltration from early phase in diabetes mellitus. Precedent anti-inflammatory property of CN2 may be critical for subsequent development of interstitial renal injuriy in diabetes mellitus and a novel target in treatment of diabetes nephropathy.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
北大核心
2010年第2期142-147,171,共7页
Chinese Journal of Nephrology,Dialysis & Transplantation