白细胞介素10基因敲除加重小鼠肾脏缺血再灌注损伤模型慢性纤维化

Interleukin 10 knockout increases renal fibrosis of ischemia- reperfusion injury model mice

目的研究白细胞介素（interleukin，IL）10基因敲除后对肾脏缺血再灌注损伤（ischemicreperfusioninjury，IRI）远期修复的影响。方法分别将18只8～10周龄全身IL-10基因敲除（IL-10^-/-）小鼠（KO小鼠）和18只8～10周龄C57BL／6野生型小鼠（WT小鼠）分为假手术组（Sham组）和肾脏IRI组，构建模型。Sham组和IRI组2周、4周肾组织标本用苏木精-伊红（HE）染色和马松三色（Masson）染色观察肾脏组织形态学改变；免疫组化检测IL-18、增殖因子Ki67及转化生长因子β1（TGF-β1）的表达；Western印迹法检测TGF-β1和IL-18的表达变化。结果与WT—IRI组相比，KO-IRI组肾脏病理损害加重，肾间质纤维化，增殖因子Ki67在肾小管上皮细胞的表达显著降低（P〈0．01），纤维化指标TGF．B1表达显著增加（P〈0．01）。结论小鼠IL-10敲除后肾脏IRI的修复明显减慢，并逐渐出现纤维化，进展为慢性肾脏病。

Objective To study the effect of interleukin （IL）-10 knockout （IL-10-/-） on renal repair after renal isehemia-reperfusion injury in mice. Methods Eighteen IL-10-/- mice （KO） aged 8- 10 weeks and 18 C57BL/6 wild type mice （WT） aged 8- 10 weeks were divided into control group （Sham） and renal isehemia- reperfusion injury （IRI） group. The renal tissue morphology change was observed by Hematoxylin and eosin （HE） staining and Masson staining. The expressions of IL- 18, Ki67 and TGF-β1 were detected by immunohistoehemistry. The expression of TGF-betal and IL-18 were detected by Western blotting. Results Compared with that in WT-IRI group, in KO-IRI group renal pathological damage was more severe, renal interstitial fibrosis was visible, Ki67 expression of renal tubular epithelial cells decreased distinctly （P 〈 0.01）, the expression of TGF- beta1 increased significantly （P 〈 0.01）. Conclusion Repair slows down significantly after kidney isehemia- reperfusion injury and fibrosis occurs gradually in IL- 10-/- mice, eventually progressing to chronic kidney disease.