复方山菊对自发性高血压大鼠肾脏的保护作用及机制

Mechanisms and protective effect of compound Shanju on renal injury in spontaneously hypertensive rats

目的:观察复方山菊对自发性高血压大鼠(SHR)肾脏损伤的保护作用并分析其可能机制。方法:SHR大鼠35只,随机分5组,每组7只,分别灌服复方山菊[0.05、0.15、0.45 g/(kg.d)]和卡托普利(0.03 g/kg),WKY大鼠正常对照组7只、SHR模型组灌服等容积蒸馏水(5 ml/kg),每日1次,连续16周。尾袖法每两周测定大鼠无创尾动脉血压,16周后,HE染色观察肾小球病理组织学变化,MASSON染色肾小球胶原纤维,免疫组化法表达肾小球诱导型一氧化氮合成酶(iNOS),RT-PCR法表达肾脏转化生长因子β1(TGF-β1)mRNA。结果:复方山菊组随着剂量的增加肾小球系膜细胞和基质增生逐渐减轻,肾小管颗粒变性逐渐改善,肾间质内炎细胞浸润逐渐减少,纤维化逐渐减轻;肾小球系膜区胶原沉积逐渐减少;肾小球iNOS及TGF-β1 mRNA的表达逐渐减少。结论:复方山菊可明显减轻SHR肾小球损伤,减少其系膜区胶原沉积,下调iNOS及TGF-β1 mRNA的表达,对肾脏具有一定的保护作用。

Objective：To observe the protective effect of compound Shanju on the renal injury in spontaneously hypertensive rats（SHR） and the related protection mechanisms.Methods：Thirty-five SHRs were randomized into groups of SHR model [distilled water,5 ml/（kg·d）],compound Shanju of high,medium and low dosage [0.05,0.15 and 0.45 g/kg·d）,respectively] and captopril [0.03 g/kg·d）,（n= 7 for each].Another 7 Winstar-Kyoto（WKY）rats were included as negative control by administration of aqua destillata in a dose of 5 ml/（kg·d）that was daily applied to the groups described above for 16 weeks.Blood pressure was measured in all animals by tail cuff every 2 weeks.After 16 weeks,the primary pathologic changes of glomerulus were observed with HE staining,and collagen fiber alteration by Msson′s trichrome staining.In addition,immunohisochemical technique and RT-PCR were used to detect the expression of glomerulus iNOS protein and glomerulus TGF-β1 mRNA,respectively.Results：Compound Shanju resulted in delayed glomerular mesangial cell and matrix proliferation,checked tubular granular degeneration,gradually repaired renal interstitial inflammatory cell infiltration,reduced fibrosis and deposition of glomerular mesangial collagen with increasing intervention dose.Also,the expression of iNOS and TGF-β1 mRNA were down-regulated in glomeruli.Conclusion：Compound Shanju can significantly reduce the glomerular injury and inhibit the glomerular mesangial collagen synthesis of SHRs,suggesting that this agent may protect the kidney from injury through down-regulated iNOS and TGF-β1 mRNA expression of SHR glomerulus.