川芎嗪对糖尿病肾病大鼠肾间质巨噬细胞浸润及单核细胞趋化蛋白-1与细胞间黏附分子-1mRNA表达的影响

Effect of Ligustrazine on Macrophages Infiltration and Expression of MCP-1 mRNA and ICAM-1 mRNA in Renal Interstitium of Diabetic Nephrosisi Rats

目的观察川芎嗪(TMP)对糖尿病肾病(DN)大鼠肾间质巨噬细胞浸润及单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)mRNA表达的影响。方法选用SD大鼠,采用单侧肾切除链脲佐菌素(STZ)诱导糖尿病肾病大鼠动物模型。成模后随机分为5组,每组12只,分别为模型组,空白对照组,贝那普利(Lotensin)组,川芎嗪高、低剂量组。除空白组和模型组外,其余各组按组别,每只分别予贝那普利1.7 mg/(kg.d)、川芎嗪150,50 mg/(kg.d)灌胃,共12周。实验第4周、第8周和第12周,测定24 h尿蛋白定量;治疗12周后,免疫组化检测肾间质巨噬细胞(ED-1)表达,RT-PCR方法测定肾间质MCP-1、ICAM-1 mRNA表达。结果与空白对照组比较,模型组大鼠24 h尿蛋白定量明显升高(P<0.05),肾小管间质中ED-1明显增加(P<0.01),肾间质MCP-1、ICAM-1 mRNA表达明显上升(P<0.01)。川芎嗪高剂量组大鼠24 h尿蛋白定量明显降低,肾小管间质组织ED-1表达减少,MCP-1、ICAM-1mRNA表达明显下调,与模型组比较均有显著性差异(P<0.05)。结论川芎嗪能减轻DN大鼠肾小管间质巨噬细胞浸润,其机制可能与减少MCP-1、ICAM-1表达有关。

Objective To observe the effect of Ligustrazine on macrophages infiltration and expression of MCP - 1 mRNA and ICAM - 1 mRNA in renal interstitium of diabetic nephrosis （DN） . Methods Diabetes was induced by injecting streptozotocin af- ter uninephrectomy. 60 rats were randomly divided into 5 groups：model control group, normal control group, Lotensin group （1.7 mg·kg-1 ·d -1）,highdoseofTMP （150mg·kg-1·d -1） and low dose ofTMP（50mg·kg -1 · d-1）.Immunohistochemical method was used to examine the expression of ED - 1. The expressions of MCP - lmRNA and ICAM - 1 mRNA were detected by the method of RT - PCR. Results 24 h urine protein was increased singificantly in model control group as compared with normal control group（ P 〈 0.05 ）, and the expression of ED - 1 was （ P 〈 0.01 ） increased. The expression of MCP - 1 mRNA in high and low- dose ligustrazine groups was decreased remarkably（ P 〈 0.01 or P 〈 0.05 ）. High and low -dose ligustrazine groups could inhibit the expression of ICAM - lmRNA（P 〈0.05）. 24 - hour urine protein was lower in high dose of TMP than those in model control group（P 〈0.05）. Conclusion TMP can reduce macrophages infiltration,and its possible mechanisms may be related to inhibition of MCP - 1 and ICAM - 1 expression.