川芎嗪对IgA肾病大鼠模型足细胞的保护作用和作用机制

Protective effects of tetramethylpyrazine on podocytes of rats with IgA nephropathy

目的研究川芎嗪对IgA肾病(IgAN)大鼠模型足细胞的保护作用和作用机制。方法建立IgAN大鼠模型,按照体重匹配原则分成正常组(A组)8只、模型组(B组)12只、地塞米松组(C组)12只、川芎嗪组(D组)12只。使用生化分析仪测定24h尿蛋白,电镜观察足细胞形态,RT-PCR检测肾组织Nephrin mRNA的表达水平。结果 B、C、D组在造模成功后第4周末均出现蛋白尿,第4、8、10、12周末时24h尿蛋白总量均高于A组,偶见肉眼血尿,差异均有统计学意义(均P<0.01),但3组间的差异无统计学意义(P>0.05);在第14、16周末时,C、D组24h尿蛋白总量明显低于B组(P<0.01)。电镜下见A组足突形态正常,排列整齐,B组多数肾小球足突部分融合,C组和D组足突极少部分融合。RT-PCR检测结果 C、D组Nephrin mRNA表达水平较B组高,差异有统计学意义(P<0.01)。结论川芎嗪能降低IgAN大鼠的24h尿蛋白总量,减少足突的融合;Nephrin在IgAN大鼠模型损伤中起重要作用,川芎嗪能增加肾组织Nephrin mRNA的表达水平。

Objective To investigate the effects of tetramethylpyrazine （TMP） on podocytes of rats with IgA nephropathy. Methods Female Sprague-Dawley（SD）rats were randomly divided into 4 groups： control group （group A, n=8）, IgA nephropathy model group（group B, n=12）, dexamethasone （DXM） group（group C, n=12）and TMP group（group D, n=12）. IgA nephropathy was induced in groups B, C, D, DXM and TMP were given to groups C and D respectively. The 24h-urine protein was determined with a automatic biochemistry analyzer; the morphology of podocyte was observed with transmission electron microscope; and the expression of Nephrin mRNA was detected by RT-PCR. Results Proteinuria was presented in group B, C and D from week 4, the quantity of 24h urinary protein was al higher than that in group A （P〈0.01）; but the quantity in group C and D was signifi-cantly lower than that in group B in week 14 and 16 （P〈0.01）. Electron microscopy showed that most glomerular foot processes were fused in group B, but only few in group C and D. The expression of Nephrin mRNA in renal tissue of group C and group D was significantly higher than that of group B （P〈0.01）. Conclusion Like dexamethasone, TMP can reduce 24h-urinary protein excretion and improve foot process fusion in rat IgA nephropathy, which is associate with up-regulation of Nephrin mRNA in renal tissue.