引经药物介导三七抗肾间质纤维化及肾靶向作用研究

目的观察三七和引经药物介导的三七复方对单侧输尿管梗阻(UUO)大鼠肾间质纤维化及肾靶向作用的影响。方法将雄性SD大鼠随机分为5组:UUO组、假手术(SOR)组、三七(RN)组、引经药物介导的三七复方(CRN)组和氯沙坦(ARB)组。每组纳入18只进行检测。HE、Masson和PAS染色观察肾间质病理学改变;化学比色法测定肾组织匀浆中羟脯氨酸的含量;Real-time PCR从mRNA水平观察α-SMA、collagenⅠ和fibronectin的表达。采用Western blot、免疫组化技术观察α-SMA蛋白的表达。结果 UUO组呈进行性肾间质纤维化改变,包括小管的萎缩、扩张、炎细胞浸润、肾间质胶原的沉积以及α-SMA、collagenⅠ、fibronectin mRNA水平的升高(P<0.05)。偏相关分析显示α-SMA的表达与肾小管损伤指数呈正相关(r=0.55;P<0.05)。RN组、CRN组、ARB组与UUO组比较均不同程度地减轻了胶原在肾间质的沉积,改善了肾脏病理损害,抑制了肾小管间质α-SMA的表达(P<0.05),且CRN作用强于RN(P<0.05)。结论三七和引经药物介导的三七复方对UUO所致的大鼠肾间质纤维化的形成均有抑制作用,且CRN作用强于RN。引经药物介导的三七复方对肾间质纤维化更具靶向治疗作用。

Investigate the effects of compound radix notoginseng on renal interstitial fibrosis and kidney-targeting treatment

Objective Investigate the effects of compound Radix Notoginseng on renal interstitial fibrosis and kidney-targeting treatment.Methods 100 healthy Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral obstruction(UUO) group,sham-operation(SOR) group,Radix Notoginseng(RN) group,compound Radix Notoginseng(CRN) group and Losartan(ARB) group.After operation,RN,CRN and ARB groups were intragastric administrated with RN(3 mL/d),CRN(3 mL/d) and ARB(20 mg/(kg·d)) respectively.Each group randomly included 18 rats for statistical analysis.The histological changes of renal interstitial tissues were observed by HE,Masson and PAS staining.Total kidney collagen content was determined by measuring the amount of hydroxyproline.The mRNA of α-SMA,collagen Ⅰ and fibronectin were reverse transcribed and quantified by real-time PCR.The expression of α-SMA protein was assessed by immunohistochemistry and Western blot analysis.Results In UUO model,the obstructed kidney showed typical features of renal tubulointerstitial fibrosis,such as severe tubular loss,dilation,atrophy,infiltration of inflammatory cells, interstitial matrix deposition(P<0.05).Partial correlation assay showed that the expression of α-SMA was related to the renal tubular injury(r=0.55;P<0.05).Administration of RN,CRN and ARB improved tubulointerstitial damage and collagen matrix accumulation induced by UUO in different degree.The expression of the α-SMA at mRNA and protein levels were significantly increased in the UUO group(P<0.05),which was also suppressed by treatment with RN,CRN and ARB in different degree.Moreover,more effective role in preventing fibrosis was observed in CRN group than when compared with that of RN group.Conclusion RN and CRN can inhibit UUO-induced renal interstitial fibrosis in rats,and CRN treatment is more effective than RN in reducing interstitial fibrosis.