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目的研究阿托伐他汀对肾间质纤维化大鼠的肾脏保护机制。方法 54只Wistar大鼠随机分为假手术组(A组,n=18)、单侧输尿管结扎(unilateral ureteral obstruction,UUO)模型组(B组,n=18)、阿托伐他汀治疗组(C组,n=18)。C组于术前3天开始灌胃(阿托伐他汀10mg·kg~(-1)·d~(-1),制成混悬液),A组及B组给予等量生理盐水灌胃,分别于术后第3、7、14天处死。光镜观察肾脏病理改变,并采用免疫组织化学染色测定肾小管间质中细胞间黏附分子1(intercellular adhesion molecule 1,ICAM-1)、核因子-κB(nuclear factor-κB,NF-κB)的表达。结果 B组ICAM-1、NF-κB的表达随梗阻时间延长明显增加,C组术后第3、7、14天ICAM-1、NF-κB的表达均显著低于同期B组(P<0.05)。相关分析结果显示,第3、7、14天NF-κB的表达与同期、同组ICAM-1的表达呈正相关(P<0.05)。结论阿托伐他汀能下调肾小管间质中ICAM-1、NF-κB的表达,抑制和延缓肾间质纤维化的进展。阿托伐他汀对ICAM-1的下调作用至少部分是通过抑制NF-κB的表达而实现的。
Objective To study the renal protective mechanism of atorvastatin on renal interstitial fibrosis in rats. Methods Fifty-four Wistar rats were randomly divided into sham operation group (n = 18), unilateral ureteral obstruction (n = 18), atorvastatin treatment group Group C, n = 18). Group C received intragastric administration of atorvastatin (10 mg · kg -1 · d -1) 3 days before operation, and rats in group A and B received intragastric administration of normal saline , Were killed on the 3rd, 7th and 14th day respectively. The pathological changes of kidney were observed with light microscope, and the expression of intercellular adhesion molecule 1 (ICAM-1) and nuclear factor-κB (NF-κB) in the tubulointerstitium was detected by immunohistochemical staining expression. Results The expressions of ICAM-1 and NF-κB in group B were significantly increased with the prolongation of obstruction. The expressions of ICAM-1 and NF-κB in group C were significantly lower than those in group B at 3, 7 and 14 days after operation (P <0.05) ). Correlation analysis showed that the expression of NF-κB was positively correlated with the expression of ICAM-1 in the same group (P <0.05) on the 3rd, 7th and 14th day. Conclusions Atorvastatin can down-regulate the expression of ICAM-1 and NF-κB in the tubulointerstitium and inhibit and delay the progression of renal interstitial fibrosis. The down-regulation of ICAM-1 by atorvastatin is at least partially achieved by inhibiting the expression of NF-κB.