摘要
目的观察氟伐他汀对单侧输尿管梗阻大鼠肾间质单核细胞趋化蛋白-1(MCP-1)表达和巨噬细胞浸润的影响,探讨其抗纤维化机制。方法90只SD雌性大鼠随机分成假手术(SOR)组、单侧输尿管梗阻术(UUO)模型组和UUO+氟伐他汀治疗组(T-UUO,氟伐他汀20mg·kg-1·d-1)。于术后第1、4、7、10、14d分别处死各组大鼠。用HE及Masson染色动态观察肾脏病理变化,免疫组织化学法测定MCP-1、单核巨噬细胞抗原(ED-1)的表达。结果UUO模型组肾小管-间质MCP-1与ED-1表达较SOR组增加(P<0.05);在术后各时间点,T-UUO组大鼠肾小管-间质MCP-1、ED-1的表达及肾间质胶原相对面积较UUO模型组显著减少,但/仍高于SOR组(P<0.05)。结论氟伐他汀可通过降低MCP-1表达、减少单核/巨噬细胞浸润以抑制肾间质纤维化。
Objective:To evaluate the effect of 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on MCP-1 expression and macrophages infiltration in renal interstitium and further clarify the underlying mechanism of the treatment.Methods:Sixty female Sprague-Dawley rats underwent UUO and then received vehichle (n=30) or fluvastatin (20 mg·kg -1 ·d -1 by daily gastric gavage, n=30) during the 14 days following surgery. Additional thirty rats were sham operated. Six rats of each group were killed respectively at 1,4,7,10,14 days after UUO. Immunohistochemistry was used on renal tissue for monocyte chemoattractant protein-1(MCP-1), ED-1,which was a marker of macrophage. Histological change were also observed by HE and Masson stain.Results:Immunohistochemical staining of ED-1 positive cells showed a marked increase in macrophages infiltrate in kidney following UUO when compared to sham-operated groups at very time point. The expression of MCP-1 also increased following UUO. Fluvastatin reduced MCP-1 production and inhibited interstitial macrophages infiltrate significantly. Additionally, fluvastatin also improved the histological changes of UUO rats.Conclusion:Reduction of MCP-1 in tubules and interstitial macrophage infiltration may be an important event by which fluvastatin prevents renal injury following UUO.
出处
《中国中西医结合肾病杂志》
2005年第7期379-381,i001,共4页
Chinese Journal of Integrated Traditional and Western Nephrology