苗药结石草总提物及总生物碱对胆结石模型小鼠的保护作用及其利胆作用研究
|
摘要
目的考察苗药结石草总提物及总生物碱对高脂饮食诱导小鼠胆囊胆固醇结石形成的影响及其利胆作用。方法采用高脂饲料喂养小鼠造成胆固醇结石模型,模型复制的同时开始给药,连续给药8周,每隔7 d记录小鼠体质量;肉眼观察和拍照记录结石形成情况;检测血清中总胆固醇(TC),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C),甘油三酯(TG)的水平,并测定LXR-α、SRBI mRNA相对表达量。另设6组非造模给药组,每组10只,进行大鼠胆总管引流,观察药物的利胆作用。结果与模型组比较,结石草总提物高剂量组、生物碱部位高剂量组能较显著降低成石率(分别为50%、60%),升高血清中的HDL-C水平(P<0. 01),降低TC、TG水平(P<0. 05,P<0. 01),对LDL-C的水平没有显著影响,并能显著降低LXR-α、SRBI mRNA相对表达量(P<0. 01)。与正常组大鼠比较,总提物高剂量组、生物碱部位高剂量组能显著增加正常大鼠胆汁流量(P<0.05),并能降低胆汁中总胆红素(TBIL)、TC水平(P<0. 05),上调大鼠肝组织MRP2,BSEP m RNA相对表达量(P<0.05),下调LXR-αm RNA相对表达量(P<0.05)。结论结石草总生物碱高剂量能够抑制高脂饲料诱导的小鼠胆囊胆固醇结石形成,并对正常大鼠有明显的利胆作用。
Objective To investigate the effects of total extract and total alkaloids from Incarvillea argute Royle on cholesterol gallstone formation in mice induced by high-fat diet and the effect of choleretic effects. Methods Cholesterol stone model was induced by feeding high-fat diet to mice. The mice were continuously administered for 8 weeks. The body mass of the mice was recorded every 7 days. The formation of stones was visually observed and photographed. Serum levels of total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C),and triglyceride(TG)were detected. The relative expression of LXR-α and SRBI mRNA were measured. Six groups of normal rats(10 in each group)were given correspondent drugs. Choledochotomy and bile drainage were conducted for evaluation of choleretic effects of drugs. Results Compared with the model group,the high-dose group of total extracts and the high-dose group of alkaloids can significantly reduce the stone formation rate(50% and 60%),and increase the level of HDL-C in the serum(P<0.01)while reducing TC and TG levels(P<0.05, P<0.01); both had no significant effect on LDL-C levels. And both of them can significantly reduce the relative expression of LXR-α, SRBI mRNA(P<0.05 or P<0.01). Compared with normal rats, the high-dose group of total extract and the high-dose group of alkaloids significantly increased the bile flow in normal rats(P<0.05, P<0.01) and reduced total bilirubin(TBIL) and TC levels(P<0.05 or P<0.01). The relative expression of MRP2 and BSEP mRNA in rats' liver tissue were upregulated(P < 0.05),and the relative expression of LXR-α mRNA was downregulated(P < 0.05). Conclusion The high dose of total alkaloids of I. argute can inhibit the formation of cholesterol gallstones in the gallbladder of mice induced by high fat diet,and has obvious choleretic effect on normal rats.
Objective To investigate the effects of total extract and total alkaloids from Incarvillea argute Royle on cholesterol gallstone formation in mice induced by high-fat diet and the effect of choleretic effects. Methods Cholesterol stone model was induced by feeding high-fat diet to mice. The mice were continuously administered for 8 weeks. The body mass of the mice was recorded every 7 days. The formation of stones was visually observed and photographed. Serum levels of total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C),and triglyceride(TG)were detected. The relative expression of LXR-α and SRBI mRNA were measured. Six groups of normal rats(10 in each group)were given correspondent drugs. Choledochotomy and bile drainage were conducted for evaluation of choleretic effects of drugs. Results Compared with the model group,the high-dose group of total extracts and the high-dose group of alkaloids can significantly reduce the stone formation rate(50% and 60%),and increase the level of HDL-C in the serum(P<0.01)while reducing TC and TG levels(P<0.05, P<0.01); both had no significant effect on LDL-C levels. And both of them can significantly reduce the relative expression of LXR-α, SRBI mRNA(P<0.05 or P<0.01). Compared with normal rats, the high-dose group of total extract and the high-dose group of alkaloids significantly increased the bile flow in normal rats(P<0.05, P<0.01) and reduced total bilirubin(TBIL) and TC levels(P<0.05 or P<0.01). The relative expression of MRP2 and BSEP mRNA in rats' liver tissue were upregulated(P < 0.05),and the relative expression of LXR-α mRNA was downregulated(P < 0.05). Conclusion The high dose of total alkaloids of I. argute can inhibit the formation of cholesterol gallstones in the gallbladder of mice induced by high fat diet,and has obvious choleretic effect on normal rats.
引文
[1]中国科学院植物研究所.中国高等植物科属检索表[M].北京:科学出版社,1995:151.
[2]左爱学,杨艳,朱萍,等.两头毛的的化学成分和药理作用研究进展[J].现代药物与临床,2014,29(1):105-109.
[3]杨燕,方其仙,张梅.彝药两头毛的研究概况[J].中国民族民间医药,2018,27(09):32-34.
[4]张书伟,张莉蓉.两头毛水提物对衰老小鼠心、肝及肾组织中MDA、GSH和SOD含量的影响[J].郑州大学学报(医学版),2011,46(5):735-736.
[5]LUO Y G,YI J H,LI B G,et al.Novel ceramides and a new glucoceramide from the roots of Incarvillea arguta[J].Lipids,2004,39(9):907-913.
[6]王文栋,王红,邓为民,等.胆结石的成因及中西药预防的研究进展[J].临床合理用药杂志,2015,8(10):174-175.
[7]CAROLINE R,ALUN J.Gallstone disease[J].Education and inspirationfor general practice,2016,9(1):11-17
[8]吕迎春.健康体检人群中胆石症发病率及其相关因素分析[J].临床合理用药杂志,2014,7(11):103-104.
[9]PROTINCASA P,MOSHETTA A,PALASCIANO G.Choesterol gallstone disease[J].Lancet,2006,15(3):230-239.
[10]田雨.依泽麦布预防饮食诱导的C57BL/6鼠胆囊胆固醇结石形成的实验研究[D].沈阳:中国医科大学,2010.
[11]HODA F,GREEN R M.Hepatic canalicular membrane transport of bile salt in C57L/J and AKR/J mice:implications for cholesterol gallstone formation[J].Membrane Biol,2003,196:9-14.
[12]万波,母齐鸣,何伟.高胆固醇饮食致石大鼠胆囊黏膜和平滑肌囊性纤维化跨膜传导因子蛋白表达的改变[J].广东医学,2018,39(3):350-354.
[13]王明玮,王雪莉,邢东明,等.小檗碱在大鼠小肠及胆汁中药代动力学研究[J].中国实验方剂学杂志,2010,16(1):46-50.
[14]苗彦国,薛东波,张伟辉.胆囊胆固醇结石成因及其治疗研究进展[J].肝胆胰外科杂志,2016,28(2):155-157,177.
[15]刘美静,刘昌辉,黄小桃,等.夏佛塔苷对高脂饮食诱导C57BL/6小鼠胆固醇结石形成的抑制作用[J].中药新药与临床药理,2016,27(4):497-502.
[16]VAN E M,TWISK J,HOEKSTRA M,et al.Differential effects of scavenger recept or BI deficiency on lipid metabolism in cells of the arterial wall and in the liver[J].J Biol Chem,2003,278(26):23699-23705.
[17]王蕾.肝脏肝X受体α和雌激素受体α表达与女性胆石病关系的研究[J].诊断学理论与实践,2006,5(4):308-311.
[18]王波,胡海.亲水性胆汁酸防治胆固醇结石作用机制的研究进展[J].现代药物与临床,2018,33(7):1854-1858.
[19]邹琼宇,陈德力,黄园园,等.角蒿属植物化学成分及药理活性研究进展[J].中草药,2016,47(3):499-511.
[20]张文冲,程嘉艺,宁天一,等.不同剂量胡椒碱对C57BL6小鼠胆固醇结石作用的影响[J].辽宁中医杂志,2017,44(7):1496-1498.
[21]李勇男,吴硕东,田雨.姜黄素联合胡椒碱在预防小鼠胆囊胆固醇性结石中的作用[J].中国普外基础与临床杂志,2015,22(12):1453-1459.
[22]ZHOU D Y,YANG X S,YANG B,et al.Chemical constituents of Incarvillea arguta[J].Natural Product Research and Development,2007,19(5):807-808.
[23]MO X Y,MAI J B.Studies on chemical constituents of chloroform portion of Incarvillea argute[J].Chinese Journal of Experimental Traditional Medical Formulae,2012,18(23):128-130.
[2]左爱学,杨艳,朱萍,等.两头毛的的化学成分和药理作用研究进展[J].现代药物与临床,2014,29(1):105-109.
[3]杨燕,方其仙,张梅.彝药两头毛的研究概况[J].中国民族民间医药,2018,27(09):32-34.
[4]张书伟,张莉蓉.两头毛水提物对衰老小鼠心、肝及肾组织中MDA、GSH和SOD含量的影响[J].郑州大学学报(医学版),2011,46(5):735-736.
[5]LUO Y G,YI J H,LI B G,et al.Novel ceramides and a new glucoceramide from the roots of Incarvillea arguta[J].Lipids,2004,39(9):907-913.
[6]王文栋,王红,邓为民,等.胆结石的成因及中西药预防的研究进展[J].临床合理用药杂志,2015,8(10):174-175.
[7]CAROLINE R,ALUN J.Gallstone disease[J].Education and inspirationfor general practice,2016,9(1):11-17
[8]吕迎春.健康体检人群中胆石症发病率及其相关因素分析[J].临床合理用药杂志,2014,7(11):103-104.
[9]PROTINCASA P,MOSHETTA A,PALASCIANO G.Choesterol gallstone disease[J].Lancet,2006,15(3):230-239.
[10]田雨.依泽麦布预防饮食诱导的C57BL/6鼠胆囊胆固醇结石形成的实验研究[D].沈阳:中国医科大学,2010.
[11]HODA F,GREEN R M.Hepatic canalicular membrane transport of bile salt in C57L/J and AKR/J mice:implications for cholesterol gallstone formation[J].Membrane Biol,2003,196:9-14.
[12]万波,母齐鸣,何伟.高胆固醇饮食致石大鼠胆囊黏膜和平滑肌囊性纤维化跨膜传导因子蛋白表达的改变[J].广东医学,2018,39(3):350-354.
[13]王明玮,王雪莉,邢东明,等.小檗碱在大鼠小肠及胆汁中药代动力学研究[J].中国实验方剂学杂志,2010,16(1):46-50.
[14]苗彦国,薛东波,张伟辉.胆囊胆固醇结石成因及其治疗研究进展[J].肝胆胰外科杂志,2016,28(2):155-157,177.
[15]刘美静,刘昌辉,黄小桃,等.夏佛塔苷对高脂饮食诱导C57BL/6小鼠胆固醇结石形成的抑制作用[J].中药新药与临床药理,2016,27(4):497-502.
[16]VAN E M,TWISK J,HOEKSTRA M,et al.Differential effects of scavenger recept or BI deficiency on lipid metabolism in cells of the arterial wall and in the liver[J].J Biol Chem,2003,278(26):23699-23705.
[17]王蕾.肝脏肝X受体α和雌激素受体α表达与女性胆石病关系的研究[J].诊断学理论与实践,2006,5(4):308-311.
[18]王波,胡海.亲水性胆汁酸防治胆固醇结石作用机制的研究进展[J].现代药物与临床,2018,33(7):1854-1858.
[19]邹琼宇,陈德力,黄园园,等.角蒿属植物化学成分及药理活性研究进展[J].中草药,2016,47(3):499-511.
[20]张文冲,程嘉艺,宁天一,等.不同剂量胡椒碱对C57BL6小鼠胆固醇结石作用的影响[J].辽宁中医杂志,2017,44(7):1496-1498.
[21]李勇男,吴硕东,田雨.姜黄素联合胡椒碱在预防小鼠胆囊胆固醇性结石中的作用[J].中国普外基础与临床杂志,2015,22(12):1453-1459.
[22]ZHOU D Y,YANG X S,YANG B,et al.Chemical constituents of Incarvillea arguta[J].Natural Product Research and Development,2007,19(5):807-808.
[23]MO X Y,MAI J B.Studies on chemical constituents of chloroform portion of Incarvillea argute[J].Chinese Journal of Experimental Traditional Medical Formulae,2012,18(23):128-130.