垂盆草总黄酮对APAP诱导小鼠肝损伤的保护作用

Protective effects of Sedum sarmentosum total flavonoids on acetaminophen⁃induced liver injury in mice

目的研究垂盆草总黄酮对对乙酰氨基酚(acetaminophen,APAP)所致小鼠肝损伤的保护作用及其可能的作用机制。方法将48只ICR雄性小鼠随机分为6组(n=8),正常对照组,模型组,阳性药物组(联苯双酯,300 mg/kg),垂盆草总黄酮低(150 mg/kg)、中(300 mg/kg)、高剂量组(600 mg/kg)。各组小鼠均灌胃相应药物或生理盐水,连续灌胃7 d,于第7天灌胃后1 h,除正常组外(腹腔注射生理盐水),其余各组均腹腔注射APAP 300 mg/kg进行肝损伤造模。APAP造模24 h后,采用相应的试剂盒测定肝组织和血清的生化指标,HE染色观察小鼠肝脏损伤情况,实时荧光定量PCR法检测Nrf2、HO⁃1 mRNA变化;Western blot法检测小鼠肝脏Nrf2、HO⁃1蛋白表达。结果垂盆草总黄酮降低了APAP诱导的ALT、AST、ALP、TBIL、LDH水平,降低肝脏指数和MDA水平,增加肝组织CAT、GSH水平以及SOD、GSH⁃PX活性;降低TNF⁃α、IL⁃1β、IL⁃6水平;明显改善肝脏组织病变;增加Nrf2、HO⁃1 mRNA和蛋白表达。结论垂盆草总黄酮对APAP诱导的肝损伤有一定的保护作用,其可能的作用机制是减少氧化应激和炎症反应。

AIM To study the protective effect of Sedum sarmentosum total flavonoids on liver injury induced by acetaminophen(APAP)in mice and its possible mechanism.METHODS Forty⁃eight ICR male mice were randomized into 6 groups(n=8),normal control group,model group,positive drug group(Bif,300 mg/kg),S.sarmentosum total flavonoids groups(150 mg/kg low dose,300 mg/kg medium dose group,600 mg/kg high dose).One hour after 7⁃day corresponding drug or saline administration,the mouse models of liver injury were induced by APAP 300mg/kg,except the normal group(saline injection).Twenty⁃four hours after APAP induction,the mice had determinations of biochemical parameters of liver tissue and serum by the corresponding kits;the measurement of liver damage by HE staining;the detection of the changes of Nrf2 and HO⁃1 mRNA by RT⁃PCR;and hepatic expression levels of Nrf2 and HO⁃1 by Western blot.RESULTS Pretreatment of S.sarmen⁃tosum total flavonoids decreased APAP exerted serum level of ALT,AST,ALP,TBIL,LDH;decreased liver index and MDA levels,increased CAT,GSH levels,and SOD and GSH⁃PX activities in hepatic tissues,and the content of TNF⁃α,IL⁃1β,IL⁃6;.and significantly improved liver tissue lesions and increased the expression of Nrf2 and HO⁃1 mRNA and protein.CONCLUSION S.sarmentosum total flavonoids is protective to APAP⁃in⁃duced liver injury,and their possible mechanism may be relevant to the reduced oxidative stress and inflammatory response.