目的:采用选择性集落刺激因子1受体抑制剂GW2580耗竭小鼠体内巨噬细胞,观察该作用对脂多糖（lipopolysaccharide,LPS）诱导的小鼠肾脏及全身炎症损伤的影响。方法:将9只雄性小鼠分为3组（每组3只）,在GW2580（160 mg/kg）给药第0、4、7天分别处死1组小鼠,制备脾脏单细胞悬液后,采用流式细胞术检测脾脏细胞中各时间点巨噬细胞占总细胞数百分比的变化,评估GW2580耗竭巨噬细胞的效率。GW2580干预炎症反应实验中,将另9只小鼠分为正常对照组、LPS组和GW2580+LPS组,每组3只,正常对照组不予药物处理;LPS组予腹腔注射LPS后16 h处死小鼠;GW2580+LPS组首先进行1周的GW2580灌胃,第8天予腹腔注射LPS,16 h后处死小鼠。采用酶联免疫吸附试验检测小鼠血清中肿瘤坏死因子α（tumor necrosis factor α, TNF-α）的表达量;收集小鼠血液、尿液以及肾脏组织标本,检测尿蛋白、血清中的肌酐水平,并观察肾脏组织病理改变情况。结果:GW2580可显著减少小鼠脾脏中的巨噬细胞数量,给药第0、4、7天在脾脏细胞中巨噬细胞占总细胞数的百分比分别为7.42%、4.78%和3.50%,差异有统计学意义（P<0.05）;在GW2580干预炎症反应实验中,LPS组TNF-α浓度为（126.4±16.47） pg/mL（1 pg/mL=1 ng/L）,正常对照组及GW2580+LPS组均低于最小检测值31.3 pg/mL。与LPS组相比,GW2580+LPS组小鼠的TNF-α水平明显下降,差异有统计学意义(P<0.05);肾脏组织标本检查提示GW2580+LPS组小鼠肾组织中炎症细胞浸润减少,肾小管空泡变性减轻。结论:GW2580可减少小鼠体内巨噬细胞数量,抑制体内炎症因子TNF-α水平,从而减轻肾脏组织病理损伤。

Objective: To study the effect of macrophages depletion through selective colony-stimulating factor 1(CSF 1) receptor inhibitor GW2580 on inflammatory response induced by lipopolysaccharide(LPS) in mice. Methods: Nine male mice were divided equally into three groups and sacrificed on the 0th, 4th and 7th day after administration of GW2580 (160 mg/kg), respectively. The single cell suspension of spleen were prepared and subjected to flow cytometry assay, the percentage of macrophages in spleen cells at each time point was measured and the depletion efficiency of GW2580 on macrophages was evaluated. Another 9 mice were divided into normal control group, LPS group and GW2580+LPS group with 3 mice in each group. The normal control group were sacrificed without any treatment, the mice in LPS group were sacrificed 16 hours after intraperitoneal injection of LPS, and the mice in GW2580+LPS group were injected with LPS intraperitoneally after administration of GW2580 intragastrically for 1 week and sacrificed 16 hours later. Enzyme linked immunosorbent assay (ELISA) was used to determine the level of tumor necrosis factor-alpha (TNF-α) expression in serum of mice. The creatinine in blood and urinary protein were measured and the histological changes of kidney tissue were compared among the 3 groups. Results: The GW2580 significantly reduce the number of macrophages in the spleen of mice, and the percentages of macrophages in total spleen cells were 7.42%, 4.78% and 3.50% on 0 th, 4 th and 7 th day (P<0.05) after GW2580 administration. LPS raised the level of TNF-α in LPS group (126.4±16.47 pg/mL) (1 pg/mL=1 ng/L) significantly, while the GW2580+LPS and normal control group were below the detection limit of 31.3 pg/mL(P<0.05). Compared with LPS group, GW2580+LPS group had lower level of TNF-α and less renal pathological injury with less inflammatory cells infiltration and alleviated vacuolar degeneration of kidney tubules. Conclusions: GW2580 could reduce the level of the TNF-α by depleting macrophages, alleviating renal injury caused by LPS -induced inflammation.