黄芪对实验性IgA肾病大鼠肾小管间质损害及NF-κB MCP-1表达的影响

Effects of astragalus on renal tubulointerestitial lesions and expression of NF-κB and MCP-1 in renal tissues in rat experimental IgA nephropathy

目的观察黄芪对实验性IgA肾病大鼠肾间质损害及肾组织核转录因子-κB(NF-κB)、单核细胞趋化蛋白(MCP-1)表达的影响,探讨黄芪防治IgA肾病肾小管间质损害的作用机制。方法28只SD大鼠分为模型组、干预组、对照组3组。模型组和干预组复制IgA肾病模型,干预组给予黄芪颗粒剂口服,并以正常SD大鼠为对照组。应用全自动生化分析仪检测尿红细胞、24h尿蛋白定量、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性;应用免疫荧光法检测肾组织冰冻切片IgA免疫复合物沉积情况,利用免疫组织化学方法,观察大鼠肾组织NF-κBp65,MCP-1表达的影响;半定量评分法计算病理积分以观察肾脏病理损害程度。结果①干预组大鼠的尿红细胞、尿蛋白、尿NAG酶含量较模型组明显降低,差异有统计学意义(P<0.01);②模型组大鼠肾组织NF-κB、MCP-1的表达与干预组、对照组相比均明显增高(P<0.01),差异有统计学意义;③干预组大鼠肾脏病理评分较模型组明显降低,差异有统计学意义(P<0.01)。结论黄芪能减轻模型组大鼠的尿红细胞数、尿蛋白和尿NAG酶活性;能减轻IgA肾病模型大鼠肾小管间质病理损害,其减轻肾小管间质损害作用可能与下调NF-κB,MCP-1表达有关。

Objective To investigate the effects of astragalus on tubulointerstitial lesions in rats with IgA nephropathy （IgAN） and to explore the possible mechanism. Methods Twenty-eight Sprague-Dawley rats were randomly assigned to three groups. The rat model of IgA nephropathy was induced by intragastric administration of bovine serum albumin and injections of LPS and CC14. Six weeks later, the rats with IgAN were randomly treated with oral astragalus （3 g/kg · d, for 6 weeks） or normal saline. Normal control rats which were not subjected to IgAN were treated with normal saline. The number of urinary erythrocytes and urinary protein and B-D-N-Acetyl glucosaminidase （NAG） contents were determined by Pan-automatic biochemistry analyzing meter. Expression of monocyte chemotactic protein-1 （ MCP-1 ） and nuclear factorkappa B （NF-KB） in tubulointerstitial tissues were analyzed by immunohistochemistry. A semiquantitative score was used to evaluate the degree of renal pathologic lesions. Results The number of urinary erythrocytes （74.02 =t 16.58 / μL vs 383.23 =t 4.94/μL） and urinary protein （13.88 =t 4.94 vs 59.82 =t 14.73 mg/L） and NAG contents （2.84 =t 0.31 vs 5.24 =1：0.80 U/L） in the astragalus-treated IgAN rats decreased remarkably compared with those in the IgAN rats without astragalus treatment （P 〈 0.01 ）. Expression of the NF-KB and MCP-1 in the renal tissues in the IgAN rats without astragalus treatment was significantly higher than that in the astragalus-treated IgAN rats and normal control rats （P 〈 0.01 ）. There were significant differences in the scores of renal pathologic lesions between the IgAN rats with or without astragalus treatment （6.03 =t 0.46 vs 10.57 =t 1.23 ; P 〈 0.01 ）. Conclusions Astragalus can decrease the number of urinary erythrocytes and urinary protein and NAG contents, and relieves tubulointerstitial lesions, possibly through the down- regulation of NF-KB and MCP-1 expression in rats with IgAN.