桃红化浊丸对非酒精性脂肪性肝病大鼠的影响
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摘要
目的探讨桃红化浊丸对非酒精性脂肪性肝病(NAFLD)大鼠的影响。方法 52只大鼠随机分为空白对照组(10只,普通饲料)和造模组(42只,高脂饲料),4周后两组分别随机抽取2只作组织切片。造模组大鼠随机均分为模型对照组(蒸馏水),水飞蓟宾组(0.35 mg/kg),桃红化浊丸高(3.08 g/kg)、中(1.54 g/kg)、低(0.77 g/kg)剂量组,各组灌胃给药4周。然后,腹主动脉取血,称量肝湿重,计算肝脏指数,检测血清生化指标水平,以及肝组织中SREBP-2、FASN及其mRNA表达。结果与模型对照组比较,水飞蓟宾组、桃红化浊丸组大鼠体质量、肝脏指数均显著降低(P<0.05),TC、TG、LDL-C、ALT、AST水平显著降低(P<0.05),HDL-C水平显著升高(P<0.05)。桃红化浊丸组肝脂肪变性有所改善,与模型对照组比较NAS积分,SREBP-2、FASN及其mRNA表达显著降低(P<0.05)。结论桃红化浊丸可降低NAFLD大鼠血脂,减轻肝细胞损伤,改善肝脂肪变性,其机制可能是通过降低SREBP-2、FASN表达实现的。
AIM To explore the effects of Taohong Huazhuo Pills on rats with non-alcoholic fatty liver disease( NAFLD). METHODS Fifty-two rats were randomly divided into blank control group( n = 10) for normal dietary management and model group( n = 42) for high-fat diet,and two rats randomly selected from each group had their conditions identified by tissue section four weeks later. Subsequently the rat models randomly and equally divided into model control group( distilled water),silibinin group( 0. 35 mg/kg),high dose Taohong Huazhuo Pills group( 3. 08 g/kg),medium dose Taohong Huazhuo Pills group( 1. 54 g/kg) and low dose Taohong Huazhuo Pills group( 0. 77 g/kg),received the corresponding four-week intragastric administration,after which their data of serum biochemical levels,and hepatic SREBP-2,FASN and their mRNA expressions were achieved from procured abdominal aortic blood and wet livers. RESULTS Compared with the model control group,silibinin group and Taohong Huazhuo Pills groups shared more significantly decreased rat body weights and levels of liver indices( P <0. 05) and lower levels of TC,TG,LDL-C,ALT,AST( P < 0. 05),and significantly increased level of HDL-C( P < 0. 05). Groups subjected to Taohong Huazhuo Pills were observed with improved hepatic steatosis,and significantly decreased NAS score and SREBP-2, FASN and their mRNA expressions( P < 0. 05).CONCLUSION Taohong Huazhuo Pills can help to achieve improvements in blood lipid profile,hepatocytic injury and hepatic steatosis due to its inhibition on the expressions of SREBP-2 and FASN.
AIM To explore the effects of Taohong Huazhuo Pills on rats with non-alcoholic fatty liver disease( NAFLD). METHODS Fifty-two rats were randomly divided into blank control group( n = 10) for normal dietary management and model group( n = 42) for high-fat diet,and two rats randomly selected from each group had their conditions identified by tissue section four weeks later. Subsequently the rat models randomly and equally divided into model control group( distilled water),silibinin group( 0. 35 mg/kg),high dose Taohong Huazhuo Pills group( 3. 08 g/kg),medium dose Taohong Huazhuo Pills group( 1. 54 g/kg) and low dose Taohong Huazhuo Pills group( 0. 77 g/kg),received the corresponding four-week intragastric administration,after which their data of serum biochemical levels,and hepatic SREBP-2,FASN and their mRNA expressions were achieved from procured abdominal aortic blood and wet livers. RESULTS Compared with the model control group,silibinin group and Taohong Huazhuo Pills groups shared more significantly decreased rat body weights and levels of liver indices( P <0. 05) and lower levels of TC,TG,LDL-C,ALT,AST( P < 0. 05),and significantly increased level of HDL-C( P < 0. 05). Groups subjected to Taohong Huazhuo Pills were observed with improved hepatic steatosis,and significantly decreased NAS score and SREBP-2, FASN and their mRNA expressions( P < 0. 05).CONCLUSION Taohong Huazhuo Pills can help to achieve improvements in blood lipid profile,hepatocytic injury and hepatic steatosis due to its inhibition on the expressions of SREBP-2 and FASN.
引文
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[7]丁洁,王亮,李娟,等.高脂乳剂灌胃构建大鼠非酒精性脂肪性肝病模型可靠性的再研究[J].临床肝胆病杂志,2012,28(7):531-534.
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[10]孔思明,张晓琳,叶菲.内质网应激与非酒精性脂肪性肝病[J].国际药学研究杂志,2016,43(2):234-238,248.
[11]Ronis M J,Baumgardner J N,Marecki J C,et al.Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition[J].Physiol Genomics,2012,44(22):1073-1089.
[12]Christoph D,Marc-Oliver R,Georgi K,et al.Expression of fatty acid synthase in nonalcoholic fatty liver disease[J].Int J Clin Exp Pathol,2010,3(5):505-514.
[13]Abdel-Magid A F.Fatty acid synthase(FASN)inhibitors as potential treatment for cancer,obesity,and liver related disorders[J].ACS Med Chem Lett,2015,6(8):838-839.
[14]Dongiovanni P,Romeo S,Valenti L.Genetic factors in the pathogenesis of nonalcoholic fatty liver and steatohepatitis[J].Biomed Res Int,2015,2015:460190.
[15]张美琳.SREBP-2诱导肝细胞成脂的研究[D].长春:吉林大学,2016.
[16]Ham J R,Lee H I,Choi R Y,et al.Anti-steatotic and anti-inflammatory roles of syringic acid in high-fat diet-induced obese mice[J].Food Funct,2016,7(2):689-697.
[17]Zhang L J,Li C Y,Wang F,et al.Treatment with PPARαagonist clofibrate inhibits the transcription and activation of SREBPs and reduces triglyceride and cholesterol levels in liver of broiler chickens[J].PPAR Res,2015,2015:347245.
[18]陈香妮,郝建梅,袁超.杨震名老中医经验方“桃红化浊汤”治疗湿热瘀阻型肝纤维化临床效果[J].临床医学研究与实践,2016,1(3):57-58.
[2]范建高.非酒精性脂肪性肝病的研究现状与展望[J].临床肝胆病杂志,2015,31(7):999-1001.
[3]Kaswala D H,Lai M,Afdhal N H.Fibrosis assessment in nonalcoholic fatty liver disease(NAFLD)in 2016[J].Dig Dis Sci,2016,61(5):1356-1364.
[4]吕秀妹.疏肝健脾、清热利湿法治疗湿热型非酒精性脂肪性肝病的疗效观察[D].武汉:湖北中医药大学,2012.
[5]郝建梅,杨志平,黄芊,等.桃红化浊丸生产工艺研究[J].亚太传统医药,2017,13(7):15-16.
[6]陈剑明,王丙信,伏爱国,等.高脂饮食诱导非酒精性脂肪肝大鼠模型的实验研究[J].中华中医药学刊,2016,34(11):2709-2712.
[7]丁洁,王亮,李娟,等.高脂乳剂灌胃构建大鼠非酒精性脂肪性肝病模型可靠性的再研究[J].临床肝胆病杂志,2012,28(7):531-534.
[8]Neuschwander-Tetri B A,Clark J M,Bass N M,et al.Clinical,laboratory and histological associations in adults with non-al-coholic fatty liver disease[J].Hepatology,2010,52(3):913-924.
[9]中华医学会肝病学分会脂肪肝和酒精性肝病学组.中国非酒精性脂肪性肝病诊疗指南(2010年修订版)[J].中国医学前沿杂志(电子版),2012,4(7):4-10.
[10]孔思明,张晓琳,叶菲.内质网应激与非酒精性脂肪性肝病[J].国际药学研究杂志,2016,43(2):234-238,248.
[11]Ronis M J,Baumgardner J N,Marecki J C,et al.Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition[J].Physiol Genomics,2012,44(22):1073-1089.
[12]Christoph D,Marc-Oliver R,Georgi K,et al.Expression of fatty acid synthase in nonalcoholic fatty liver disease[J].Int J Clin Exp Pathol,2010,3(5):505-514.
[13]Abdel-Magid A F.Fatty acid synthase(FASN)inhibitors as potential treatment for cancer,obesity,and liver related disorders[J].ACS Med Chem Lett,2015,6(8):838-839.
[14]Dongiovanni P,Romeo S,Valenti L.Genetic factors in the pathogenesis of nonalcoholic fatty liver and steatohepatitis[J].Biomed Res Int,2015,2015:460190.
[15]张美琳.SREBP-2诱导肝细胞成脂的研究[D].长春:吉林大学,2016.
[16]Ham J R,Lee H I,Choi R Y,et al.Anti-steatotic and anti-inflammatory roles of syringic acid in high-fat diet-induced obese mice[J].Food Funct,2016,7(2):689-697.
[17]Zhang L J,Li C Y,Wang F,et al.Treatment with PPARαagonist clofibrate inhibits the transcription and activation of SREBPs and reduces triglyceride and cholesterol levels in liver of broiler chickens[J].PPAR Res,2015,2015:347245.
[18]陈香妮,郝建梅,袁超.杨震名老中医经验方“桃红化浊汤”治疗湿热瘀阻型肝纤维化临床效果[J].临床医学研究与实践,2016,1(3):57-58.