摘要
目的探讨参苓白术丸对原发性高胆固醇血症豚鼠模型的影响。方法60只雄性Hartley豚鼠,分为对照组,模型组,依折麦布组,参苓白术丸高、中、低剂量组,每组10只。对照组给予普通饲料,其余组均给予高脂饲料,建立外源性高胆固醇血症豚鼠模型。造模4周后开始药物灌胃干预,依折麦布组予依折麦布混悬液1 mg/kg,参苓白术丸高、中、低剂量组分别予17.00、8.50、0.85 g/kg,模型组和对照组给予等体积生理盐水。比较各血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及胆汁TC、总胆汁酸水平;观察各组肝脏组织形态学变化;同时记录各组小肠组织尼曼-匹克C1型类蛋白1(NPC1L1)、三磷酸腺苷结合盒转运体G5(ABCG5)、胆固醇酰基转移酶2(ACAT2)及肝脏X受体α(LXRα)的表达水平。结果与对照组比较,模型组血清TG、TC、LDL-C及胆汁TG、总胆汁酸水平均升高(P<0.05)。与模型组比较,参苓白术丸低剂量组血清TG水平降低(P<0.05);参苓白术丸中剂量组血清TC、LDL-C水平均降低,HDL-C水平升高(P<0.05);参苓白术丸高剂量组血清TG、TC、LDL-C水平均降低,HDL-C水平升高(P<0.05);参苓白术丸中、高剂量组胆汁TC、总胆汁酸水平均降低(P<0.05)。对照组肝脏组织基本正常;模型组可见弥漫性大泡性脂肪变,肝组织内广泛的肝细胞气球样变、少量炎症细胞浸润和点状细胞坏死;参苓白术丸中、高剂量组脂肪变性及肝细胞气球样变显著减轻;参苓白术丸低剂量组肝细胞脂肪样变性改善较模型组不明显。与对照组比较,模型组NPC1L1、ACAT2、ABCG5、LXRα水平均升高(P<0.05)。与模型组比较,参苓白术丸中、高剂量组NPC1L1、ACAT2、LXRα水平均降低,ABCG5水平均升高(P<0.05)。结论参苓白术丸中、高剂量可以缓解高胆固醇饮食诱导的高脂血症,减轻肝细胞脂肪变性,抑制原发性高胆固醇血症豚鼠模型小肠组织中NPC1L1、ACAT2及LXRα的表达,上调ABCG5的表达。
Objective To investigate the effect of Shenling Baizhu Pills on guinea pigs model with primary hypercholesterolemia.Methods Sixty male Hartley guinea pigs were divided into control group,model group,Ezetimibe group,Shenling Baizhu Pills high-dose,medium-dose,and low-dose groups,with ten guinea pigs in each group.The control group was given ordinary diet,and the other groups were given high fat diet to establish the guinea pigs model of exogenous hypercholesterolemia.Four weeks after modeling,drug gavage intervention was started.Ezetimibe group was given Ezetimibe suspension 1 mg/kg,Shenling Baizhu pills high-dose,medium-dose,and low-dose groups were given 17.00,8.50 and 0.85 g/kg,respectively,model group and control group were given equal volume of normal saline.The levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),bile TC and total bile acid were compared.The histomorphological changes of liver in each groups were observed.Meanwhile,the expression levels of Niemann-Pick type C1 like protein 1(NPC1 L1),ATP binding cassette transport G5(ABCG5),acyl-Co A cholesterol acyltransferase 2(ACAT2) and liver X receptor α(LXRα) in each groups were recorded.Results Compared with control group,the serum levels of TG,TC,LDL-C,bile TC,and total bile acid in model groupwere increased(P < 0.05).Compared with model group,the level of serum TG in Shenling Baizhu Pills low-dose group was decreased(P < 0.05);the levels of TG and LDL-C in Shenling Baizhu Pills medium-dose group were decreased,while the level of HDL-C was increased(P < 0.05);the serum levels of TG,TC,and LDL-C in Shenling Baizhu Pills high-dose group were decreased,while the level of HDL-C was increased(P < 0.05);the levels of bile TC and total bile acid in Shenling Baizhu Pills medium-dose and high-dose groups were decreased(P < 0.05).The liver tissue of control group was normal;in model group,diffuse bullae steatosis,extensive balloonlike change of liver cells,a small amount of inflammatory cell infiltration and dot cell necrosis were observed;steatosis and hepatocyte balloon-like change were significantly reduced in Shenling Baizhu Pills medium-dose and high-dose groups;the improvement of hepatic adipose degeneration in Shenling Baizhu Pills low-dose group was not obvious compared with model group.Compared with control group,the levels of NPC1 L1,ACAT2,ABCG5,and LXRα in model group were increased(P <0.05).Compared with model group,the levels of NPC1 L1,ACAT2,and LXRα in Shenling Baizhu Pills medium-dose and high-dose groups were decreased,while the levels of ABCG5 were increased(P < 0.05).Conclusion Shenling Baizhu Pills medium-dose and high-dose can alleviate hyperlipidemia induced by high cholesterol diet and reduce hepatocyte steatosis,inhibit the expression of NPC1 L1,ACAT2,and LXRα in small intestine of guinea pigs model with primary hypercholesterolemia,and up-regulate the expression of ABCG5.
作者
张雨田
王红
屈子怡
杨朝帅
冯彬彬
王悦豪
ZHANG Yutian;WANG Hong;QU Ziyi;YANG Chaoshuai;FENG Binbin;WANG Yuehao(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin 300000,China;Department of General Surgery,the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300000,China)
出处
《中国医药导报》
CAS
2021年第30期33-37,共5页
China Medical Herald
基金
天津市滨海新区联合攻关项目(2014BWKL001)。
