山楂叶总黄酮对非酒精性脂肪性肝炎大鼠组织COX―2Nrf2表达影响.docVIP

山楂叶总黄酮对非酒精性脂肪性肝炎大鼠组织COX―2Nrf2表达影响 　　[摘要]观察山楂叶总黄酮（THFL）对非酒精性脂肪性肝炎（NASH）大鼠肝脏COX-2/Nrf2表达的影响，探讨其抗NASH的作用机制。32只SD大鼠随机分成正常组、模型组、THFL高剂量组及THFL低剂量组，每组8只，以高脂饮食12周建立NASH大鼠模型，同时以250，125 mg?kg-1?d-1的TFHL进行干预，常规HE染色观察大鼠肝组织脂肪变和炎症程度，比色法测定T-AOC水平，免疫组织化学法检测肝组织8-OHdG 水平及COX-2，Nrf2，HO-1蛋白表达，Real time-PCR法检测肝组织中COX-2，Nrf2，HO-1 mRNA表达。模型组大鼠肝组织脂肪变和炎症程度气球样变及NAFLD活动度积分（NAS）较正常组明显增强，总抗氧化能力（T-AOC）下降，DNA损害标志物8-OHdG水平增加，COX-2，Nrf2，HO-1 mRNA和蛋白表达较正常组显著增强；应用高、低剂量的TFHL干预后，肝组织炎症程度和NAS较模型组显著降低，8-OHdG水平、COX-2 mRNA和蛋白表达较模型组减少，Nrf2 和HO-1 mRNA和蛋白的表达则较模型组显著增高。COX-2/Nrf2通路参与高脂饮食诱导的NASH的发生发展，TFHL能通过进一步促进Nrf2/HO-1表达，从而负调节 COX-2，抑制COX-2的过表达，减轻氧化反应导致的细胞损伤和肝组织炎症，防止NASH的进展。 　　[关键词]山楂；黄酮；非酒精性脂肪性肝炎；氧化应激；COX-2；Nrf2 　　[Abstract]To explore the effect of total flavones from hawthorn leaf on （THFL） on the expression of COX-2/Nrf2 in the liver tissues of rats with nonalcoholic steatohepatitis （NASH）， and discuss its anti-NASH mechanism， thirty-two SD rats were randomly divided into the normal group， model group， THFL high dose group and low dose group，8 in each group. High fat diet was given to the rats for 12 weeks to establish the NASH models， and the high and low dose groups were administered with TFHL at the dosage of 250， 125 mg?kg-1?d-1respectively. Steatosis and the inflammatory changes of the liver tissues in rats were observed by HE staining； T-AOC level was detected by colorimetry； the level of 8-OHdG and the protein expressions of COX-2， Nrf2 and HO-1 in the liver tissues were determined by immunohistochemistry； and the mRNA expressions of COX-2， Nrf2 and HO-1 in liver tissues were detected by Real time-PCR. Compared with the normal group， the liver steatosis， ballooning degeneration for inflammatory degree and NAFLD activity scores （NAS） were significantly increased in model group， while total antioxidant capacity （T-AOC） was decreased， DNA damage marker 8-OHdG level was increased， and the mRNA and protein expressions of COX-2， Nrf2 and HO-1 were significantly increased. After the administration of hi