中文摘要：

目的通过敲低肾组织高迁移率族蛋白1（HMGB1）表达，探讨其对改善狼疮肾炎小鼠肾功能，降低肾小球细胞增殖水平的影响。方法MRL／Faslpr鼠（n=24）被随机分为模型组、shHMGB1组和空质粒组；选取周龄、体质量相匹配的MRL／MpJ鼠为健康对照组。shHMGB1组和空质粒组采用电穿孔转染技术分别转染shHMGB1质粒和空质粒，模型组和健康对照组仅转染生理盐水。用全自动生化分析仪检测小鼠血清尿素氮和肌酐水平，测定尿蛋白浓度并计算24h尿蛋白量（UP）。HE染色观察肾组织的形态学表现；免疫荧光和Western印迹法检测小鼠肾小球中HMGB1和增殖细胞核抗原（PCNA）的表达；实时定量PCR法检测小鼠肾小球HMGB1和PCNAmRNA表达变化。结果（1）与健康对照组相比，模型组小鼠肾小球HMGB1mRNA和蛋白的表达升高（均P〈0．05）；与模型组相比，shHMGB1组小鼠肾小球中HMGB1mRNA和蛋白的表达降低（均P〈0．05）。（2）与模型组相比，shHMGB1组小鼠尿蛋白减少（P〈0．05）。（3）免疫荧光和Western印迹结果显示，与健康对照组相比，模型组小鼠肾小球中PCNAmRNA和蛋白表达升高（P〈0．05）。与模型组相比，shHMGB1组肾小球中PCNA表达降低（P〈0．05）。结论敲低肾组织HMGB1表达可改善狼疮肾炎小鼠的肾功能，降低肾小球细胞的增殖水平。

英文摘要：

Objective To investigate the effect of high mobility group box chromosomal protein 1 （HMGBI） knockdown on improving renal function and decreasing cell proliferation of glomeruli in lupus nephritis （LN） MRL/Faslpr mice. Methods Twenty-four MRL/Faslpr mice were randomly divided into 3 groups： LN model group, shHMGB1 group and empty plasmid group. Besides, eight MRL/MpJ mice, age and mass matched to the MRL/Faslpr mice, were chosen as normal control group （shNC group）. Electroporation technology was used for in vivo transfection in treatment group. shHMGB1 group and empty plasmid group were transfeeted by electroporation technology for shHMGB1 plasmids and empty plasmid, LN model group and normal control group were transfected only with saline. Automatic biochemical analyzer was used to detect serum urea nitrogen （BUN） and creatinine （Scr） levels and 24 h urinary protein （UP） was tested. HE staining was used to detect the pathological change of renal tissues; real-time PCR, immunofluorenee staining and Western blotting were used to detect the mRNA and protein expression of HMGB1 and PCNA. Results （1） The HMGB1 mRNA and protein expression in LN group increased compared with those in control group, HMGB1 mRNA and protein expression in shHMGB1 group reduced compared with those in LN model group （all P 〈 0.05）. （2） 24 h UP of MRL/Faslpr mice in shHMGB1 group significantly reduced compared with those in LN group （P 〈 0.05）. （3） Immunofluorence and Western blotting showed that positive signal of proliferating cell nuclear antigen （PCNA） was mainly located in nuclei, PCNA mRNA and protein in glomeruli of LN model group increased compared with those of control mice （P 〈 0.05）. Interestingly, PCNA expression in glomeruli of shHMGB1 group remarkably reduced （P 〈 0.05）. Conclusions shHMGB1 significantly improves renal function and decreases cell proliferation of glomeruli in LN MRL/Faslpr mice.