蛋白激酶Cβ抑制剂LY333531对阿霉素肾病小鼠肾脏的保护作用

Effect of protein kinase C beta inhibitor LY333531 on macrophage infiltration in the kidney of mice with adriamycin nephropathy

目的:探讨蛋白激酶Cβ抑制剂LY333531对阿霉素肾病小鼠肾脏的保护作用。方法:24只雄性、8周龄BALB/c小鼠随机分为肾病组、治疗组和对照组(n=8),肾病组和治疗组一次性尾静脉注射阿霉素(10mg/kg),对照组注射等量生理盐水;阿霉素注射后第5天,治疗组予LY33353110mg/(kg·d)灌胃,肾病组和对照组予等量溶媒灌胃。阿霉素注射后2周处死小鼠。处死前留取尿标本检测尿蛋白和肌酐。观察肾脏病理、巨噬细胞浸润、巨噬细胞移动抑制因子(MIF)和单核细胞趋化蛋白-1(MCP-1)的表达。结果:与对照组相比,肾病组尿蛋白肌酐比值升高,肾脏巨噬细胞浸润、MCP-1和MIF表达增加(P<0.01);与肾病组相比,治疗组尿蛋白/肌酐比值下降,肾脏巨噬细胞浸润、MCP-1和MIF表达减少(P<0.01)。结论:LY333531对阿霉素肾病小鼠肾脏具有保护作用,其机制可能与下调阿霉素肾病小鼠肾脏MCP-1和MIF表达,抑制巨噬细胞浸润有关。

Objective To investigate the effect of protein kinase C （PKC） [3 inhibitor LY333531 on macrophage infiltration in the kidney of mice with adriamycin nephropathy. Methods Twenty-four male 8 weeks old BALB/c mice were randomly assigned into 3 groups （each n = 8）, mice in adriamycin nephropathy group and LY333531 treated group received a single intravenous injection of adriamycin （ 10 mg/kg）, while those in normal control group received equal volume of saline. Mice in LY333531 treated group received 10 mg/kg of LY333531 （intragastric administration） at day 5 after adriamycin injection, while those in adriamycin nephropathy group and normal control group received equal volume of vehicle. All the mice were sacrificed 2 weeks after the induction of nephropathy. And then urinary protein, ereatinine, maerophage migration inhibitory factor （MIF）, and biochemical indicators in blood were measured. Pathological changes, infiltration of macrophage, and expression of MIF in the kidneys were observed. Results Expressions of MIF and the infiltration of maerophage were increased in the kidneys of mice 2 weeks after the induction of nephropathy, but those were significantly lower in LY333531 treated group as compared with those in adriamycin nephropathy group. Conclusions LY333531 could protect the kidneys of mice with adriamycin nephropathy, which may be associated with the inhibition of the expression of MIF and macrophage infiltration.