慢肾康宁对腺嘌呤致肾间质纤维化大鼠的影响

Effect of Manshenkangning prescription on kidneys of renal interstitial fibrosis rats caused by adenine

目的研究慢肾康宁对腺嘌呤致肾间质纤维化大鼠的保护作用,并探讨其可能的作用机制。方法将Wistar雄性大鼠60只分成正常组、模型组、对照组(给予氯沙坦10 mg·kg-1·d-1)和高、中、低剂量实验组(分别给予慢肾康宁30,15,7.5 mg·kg-1·d-1)。用腺嘌呤灌胃(250 mg·kg-1·d-1)诱导肾间质纤维化大鼠模型,2 h后给予上述药物进行灌胃,造模周期为连续21 d,给药时间连续30 d。用生化法测定血清肌酸酐(SCr)、尿素氮(BUN)、24 h尿蛋白定量(24 h MTP)水平和肾小球滤过率(eGFR);以苏木素-伊红(HE)染色法观察大鼠肾组织病理改变情况;以马松(Masson)染色观察大鼠肾胶原沉积情况。结果模型组和高、中、低剂量实验组SCr分别为(340.00±22.99),(176.80±18.60),(234.75±13.59),(266.11±14.78)μmol·L-1;BUN分别为(23.74±2.51),(14.53±2.25),(18.78±0.88),(18.90±2.14)mmol·L-1;24 h MTP分别为(675.86±74.58),(323.81±41.83),(438.84±34.69),(493.76±37.04)mg·d-1;eGFR分别为(19.30±2.48),(49.96±10.95),(32.61±10.75),(27.18±5.98)mL·min-1,与正常组相比,差异均有统计学意义(均P<0.05)。HE染色和Masson染色结果显示,与正常组比较,模型组肾间质损伤严重且肾间质胶原物质大量沉积,实验组肾间质小管损伤减轻,肾间质胶原物质沉积减少,差异均有统计学意义(均P<0.01)。结论慢肾康宁具有护肾作用,可显著改善肾间质纤维化大鼠的间质化进展状态,其可能的机制与调控肾SIRT1活性,抑制COX-2表达,以抵抗肾炎症反应,提高肾的抗氧化应激能力,从而延缓慢性肾衰竭的发生、发展。

Objective To study the protective effect of Manshen Kangning on adenine-induced renal interstitial fibrosis in rats and explore its possible mechanism.Methods Sixty Wistar male rats were divided into normal group,model group,control group(10 mg·kg-1·d-1losartan)and high,medium,low dose experimental groups(30,15,7.5mg·kg-1·d-1Manshenkangning).Rat models of renal interstitial fibrosis were induced by intragastric administration of adenine(250mg·kg-1·d-1).After 2 h,the above drugs were administered intragastrically for 21 consecutive days,and the administration time was 30consecutive days.Serum creatinine(SCr),urea nitrogen(BUN),24 h urinary protein(24 h MTP)and glomerular filtration rate(eGFR)were measured by biochemical method;renal histopathological changes were observed by hematoxylin-eosin(HE)staining.Results The SCr in model group and high,medium,low dose experimental groups were(340.00±22.99),(176.80±18.60),(234.75±13.59),(266.11±14.78)μmol·L-1,BUN were(23.74±2.51),(14.53±2.25),(18.78±0.88),(18.90±2.14)mmol·L-1;24 h MTP were(675.86±74.58),(323.81±41.83),(438.84±34.69),(493.76±37.04)mg·d-1;eGFR were(19.30±2.48),(49.96±10.95),(32.61±10.75),(27.18±5.98)mL·min-1,all had significant difference compared with normal group(all P<0.05).HE staining and Masson staining showed that compared with normal group,the renal interstitial lesions in model group were severe and the renal interstitial collagen material was deposited in a large amount.The renal interstitial tubule injury was relieved and the renal interstitial collagen deposition was reduced in experimental groups.Conclusion Manshenkangning can significantly protect the kidney to against the progress of interstitial fibrosis in rats.Its possible mechanism is to regulate the activity of SIRT1 and inhibit the expression of COX-2 in order to resist the inflammatory reaction of kidney and improve the ability of anti-oxidative stress of kidney,thus delaying the occurrence and development of chronic renal failure.