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三七对酒精性肝病大鼠肝组织SREBP1c表达的影响 被引量:2

Effect of Sanchi on hepatic expression of SREBP1c in rats with alcoholic liver disease
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摘要 目的:观察三七对酒精性肝病(ALD)大鼠肝组织固醇调节元件结合蛋白(SREBP)1c表达的影响。方法:110只雄性SD大鼠随机分为正常组30只,模型组35只,三七高、低剂量组和硫普罗宁组各15只,连续14周白酒-玉米油-吡唑混合液灌胃建立ALD模型,同时三七高、低剂量组和硫普罗宁组分别灌服1.2、0.6 g/(kg.d)的三七粉及0.1 g/(kg.d)的硫普罗宁;4周、8周、14周分别处死正常组大鼠10只,模型组8只;14周处死剩余大鼠。光镜观察肝脂肪变、炎症及纤维化程度,RT-PCR法检测肝组织SREBP1c及其下游靶基因乙酰辅酶A合成酶(ACS)、脂肪酸合成酶(FAS)mRNA表达,免疫组化法检测肝组织SREBP1c蛋白表达。结果:(1)各时间点模型组大鼠肝组织脂肪变及炎症程度计分较同期正常组明显增高(P<0.01)。(2)正常组大鼠肝脏可见一定量SREBP1c、ACS、FAS mRNA表达,随时间延长模型组大鼠3个基因的表达均逐步增加,8周、14周时较正常组和模型4周组明显增高(P<0.01或0.05)。(3)模型8周、14周组较同期正常组肝组织SREBP1c表达明显增高(P<0.01或0.05)。(4)三七高、低剂量组及硫普罗宁组大鼠14周肝组织脂肪变及炎症程度、肝脏SREBP1c蛋白以及3个目标基因的表达均较模型组明显降低(P<0.01或0.05)。结论:三七可明显减轻ALD大鼠肝组织脂肪变和炎症程度,抑制肝脏脂代谢关键信号分子SREBP1c mRNA和蛋白及其靶基因ACS、FASmRNA的表达,从而改善肝组织病理,阻止ALD的慢性化进程。 AIM: To evaluate the effect of Sanchi on hepatic expression of sterol regulatory element binding protein(SREBP)-1c in rats with alcoholic liver disease(ALD). METHODS: 110 SD male rats were divided into normal group(n=30),control group(n=35),high-dose Sanchi group(n=15),low-dose Sanchi group(n=15) and Tiopronin group(n=15) randomly.A formula of ethanol-corn oil-pyrazole mixture was selected to induce ALD model by feeding for 14 weeks continually.Meanwhile,rats of high-dose Sanchi group,low-dose Sanchi group and Tiopronin group were administered with 1.2 g/(kg·d) Sanchi,0.6 g/(kg·d) Sanchi and 0.1 g/(kg·d) Tiopronin respectively.For investigating dynamic histologic changes,10 rats in normal group and 8 rats in control group were sacrificed at the 4th week,8th week,14th week by turns,and the others were sacrificed at 14th week.Histopathological scores were assessed by microscopic examination of HE and Masson staining of the right lobe of liver.The hepatic expression of SREBP1c were detected with immunohistochemistry,mRNA levels of SREBP1c and the targeting gene,acetyl-CoA-synthetase(ACS) and fatty acid synthetase(FAS) were detected by RT-PCR.RESULTS:(1)Compared with the rats in normal group,rats in control group developed higher steatosis scores and inflammation scores at every point(P0.01).(2)In normal group,the hepatic expression of SREBP1c,ACS and FAS mRNA were low,which increased significantly as the time flied in model rats(P0.01 or 0.05).(3)Hepatic expression of SREBP-1c in model group were higher than those of normal group at 8th and 14th week(P0.01or 0.05),respectively.(4)High-dose Sanchi,low-dose Sanchi,or Tiopronin ameliorated the histopathological changes remarkably(P0.01 or 0.05),the mRNA of hepatic SREBP-1c,ACS and FAS,together with SREBP-1c,were obviously inhibited(P0.01 or 0.05).CONCLUSION: Sanchi can remarkably improve the hepatic steatosis and inflammation,restrain the hepatic expression of SREBP1c,a pivotal signal regulating liver lipid metabolism,and the mRNA of hepatic SREBP1c,ACS and FAS,then delay the exacerbation of ALD.
出处 《中国临床药理学与治疗学》 CAS CSCD 2011年第2期148-154,共7页 Chinese Journal of Clinical Pharmacology and Therapeutics
基金 杭州市医药卫生科技计划项目(2006B056)
关键词 酒精性肝病 三七 固醇调节元件结合蛋白-1C Liver disease Alcoholic Rat Sanchi SREBP1c
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