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纸质出版:2014
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李里,卢松,甘华.利拉鲁肽对糖尿病大鼠肾脏巨噬细胞浸润的影响[J].陆军军医大学学报(原第三军医大学学报),2014,36(18):1909-1913.
Li Li,Lu Song,Gan Hua.Effects of liraglutide on macrophage infiltration in kidney of rats with diabetic nephropathy[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(18):1909-1913.
目的 探讨利拉鲁肽对糖尿病(diabetes mellitus,DM)大鼠肾脏巨噬细胞浸润的影响及可能的肾脏保护机制。 方法 8周龄雄性SD大鼠40只,体质量(200±25)g,分为3组:①正常对照(NC)组(n=10);②DM组(n=15);③利拉鲁肽(LR)组(n=15)。DM、LR组经高脂高糖饲养联合小剂量链脲佐菌素(streptozocin,STZ)腹腔注射诱导建立2型DM大鼠模型。NC组与LR组大鼠予利拉鲁肽100 μg/kg腹腔内注射(2次/d),DM组大鼠行生理盐水腹腔内注射。12周后采集各组大鼠血、尿标本和肾组织标本,观察各组大鼠血肌酐、尿素、24 h尿蛋白定量的改变;免疫组化法检测单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、核因子-κB(nuclear factor-κB,NF-κB)、CD68在大鼠肾组织表达的改变,RT-PCR检测MCP-1、NF-κB mRNA表达水平的改变。 结果 与NC组比较,DM组与LR组大鼠尿蛋白、尿素、血肌酐水平均明显上升(P0.01);LR组大鼠尿蛋白、尿素、血肌酐水平较DM组明显降低(P0.01);NC组大鼠肾组织MCP-1、NF-κB、CD68有少量表达,DM组大鼠肾组织MCP-1、NF-κB、CD68(肾小球、肾小管)表达明显增加,LR组大鼠肾组织MCP-1 (2.93±0.27 vs 4.64±0.38)、NF-κB (5.44±1.65 vs 9.76±1.83)、CD68(4.47±0.66 vs 7.15±0.85;2.53±0.87 vs 5.65±0.69)较DM组显著下降(P0.01)。相关性分析结果显示,肾组织MCP-1、NF-κB、CD68(肾小球、肾小管)表达与24 h尿蛋白定量呈显著正相关,肾组织CD68表达与MCP-1、NF-κB的表达呈显著正相关。 结论 利拉鲁肽可能通过抑制MCP-1、NF-κB和CD68表达,从而抑制巨噬细胞聚集,减少蛋白尿,延缓肾脏损害。
Objective To investigate the effects of liraglutide on the macrophages infiltration in kidney of rats with streptozotocin diabetes. Methods Forty adult male Sprague-Dawley rats (8 weeks old
weighting 200±25 g) were randomly divided into 3 groups: a normal control group (group NC
n=10)
a diabetes group (group DM
n=15) and a liraglutide treatment group (group LR
n=15). The rats of group DM and group LR received intra-peritoneal injection of low dose streptozotocin to induce an experimental model of type 2 diabetes after high fat and high glucose breeding. The rats of group NC and LR were treated with liraglutide (100 μg/kg twice per day) by hypodermic injection
and the rats of group DM were treated with equal volume normal saline. In 12 weeks after establishment of type 2 diabetes model
we sacrificed the rats and detected 24 h-urinary protein excretory (24 h UPE)
serum creatinine (Scr) and blood urea nitrogen (BUN). The expression of monocyte chemoattractant protein-1 (MCP-1)
nuclear factor-kappa B (NF-κB) and CD68 in the renal tissue was detected by immunohistochemical assay and reverse transcription-polymerase chain reaction (RT-PCR). Results Compared with group NC
Scr
BUN and 24 h UPE were significantly increased in the rats of group DM and group LR (P0.01). All of the above indexes were significantly lower in group LR than in group DM (P0.01). MCP-1
NF-κB and CD68 (glomerulus and tubules) were mildly expressed in the renal tissue of group NC
and their expression was significantly enhanced in the renal tissue of group DM and group LR. MCP-1 (2.93±0.27 vs 4.64±0.38)
NF-κB (5.44±1.65 vs 9.76±1.83) and CD68 (4.47±0.66 vs 7.15±0.85; 2.53±0.87 vs 5.65±0.69) levels were significantly lower in group LR than in group DM (P0.01). Correlation analysis showed that the expression of MCP-1
NF-κB and CD68 was positively correlated with 24 h UPE
and the expression of CD68 in renal tissue was positively correlated with the expression of MCP-1 and NF-κB. Conclusion Liraglutide can decrease the urine protein and ameliorate renal injury through alleviating macrophage infiltration by down-regulating the expression of MCP-1
NF-κB and CD68 in renal tissue of type 2 diabetic rats.
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