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| 参苓白术散通过“肠 -肝”轴影响胆囊胆固醇结石形成的机制探究 |
| 王红,曲鹏飞,邓为民,韩俊泉,杨景明,张雨田,杨朝帅,王悦豪,冯彬彬,李慧臻 |
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| 天津中医药大学第二附属医院天津 300000;天津市滨海新区大港医院天津 300000;天津市中医药大学研究生院天津 300000 |
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| 摘要: |
| 目的:以“肠 -肝”轴为切入点，观察参苓白术散对豚鼠胆固醇结石形成相关途径的影响，探究参苓白术散对胆固醇结石的治疗机制。方法:选取雄性 SD豚鼠 60只，随机均分为 6组，对照组予普通饲料，其余 50只豚鼠予高脂饲料，建立胆固醇结石模型。建模成功后随机分为 5组，每组 10只，分别为模型组(等量高脂饮食喂养)、参苓白术散高、中、低剂量组(17、5、0.85 g/kg)、依折麦布组( 1mg/kg)灌胃给药 2个月。生化法和酶比色法测定各豚鼠血清总胆固醇(TC)、三酰甘油( TG)；用酶显色法测定胆汁中胆汁酸、胆固醇；在甲醛溶液固定后采用苏木素 -伊红 (HE)染色，光镜下观察肝组织形态学的变化；光镜下观察胆固醇结晶；酶联免疫吸附法( ELISA法)检测豚鼠肝组织中胆囊收缩素 (CCK)、B1型清道夫受体 (SRB1)以及小肠组织 Niemann-Pick C1样蛋白 1(NPC1L1)表达水平。结果:成功建立高脂血症模型。相比对照组，模型组表现为肝脏显著脂肪变，胆汁内胆固醇浓度增高( P＜ 0.01)，并由肉眼可见胆固醇结石或结晶出现，血液血脂水平异常( P＜ 0.01)，豚鼠肝组织中 CCK、SRB1及小肠组织 NPC1L1表达水平也升高( P＜ 0.01)；与模型组比较，参苓白术散中、高剂量组的胆汁总胆固醇、总胆汁酸、血脂水平明显降低，肝组织中 CCK升高，肝组织中 SRB1和小肠组织 NPC1L1的表达水平均下降，其中高剂量组效果最明显( P＜ 0.01)。结论:参苓白术散通过降低小肠对胆固醇吸收、降低胆汁中胆固醇水平、促进胆囊运动来降低胆囊胆固醇结石形成的风险，其机制可能与降低小肠组织 NPC1L1表达，提高肝组织中 SRB1、CCK表达有关。 |
| 关键词: 参苓白术散 肠 -肝轴 胆囊收缩素 B1型清道夫受体 尼曼 -匹克 C1样蛋白 1 |
| DOI：10.3969/j.issn.1007-6948.2021.05.003 |
| 投稿时间：2021-01-03 |
| 基金项目:天津市滨海新区卫生局科技项目( 2014BWKL001) |
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| Study on the Mechanism of Shenling Baizhu Powder on the Formation of Cholecystolithiasis in the “Intestinal-liver Axis” Pathway |
| WANG Hong,QU Peng-fei,DENG Wei-ming |
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| Abstract: |
| Objective To explore the intervention mechanism of Shenling Baizhu powder on cholesterol gallstone formation in hyperlipidemic rats, and to discuss the therapeutic mechanism of Shenling Baizhu powder on cholesterol gallstone from the intestine-liver axis. Methods 60 male SD rats were selected, 10 rats were randomly selected as normal group, and the remaining 50 rats were fed with high fat diet to establish cholesterol gallstone rat model. After the successful establishment of the model, 10 rats in each group were randomly divided into ?ve groups: model group (fed with the same amount of high-fat diet), Shenling Baizhu powder high, medium and low dose groups (17,5,0.85g/kg), and 1mg/kg ezemab group, which were given intragastrically for 2 months. Determination of serum total cholesterol (TC) and triglyceride (TG); by biochemical method and enzyme colorimetry; bile acid and cholesterol in bile were determined by enzyme colorimetric method. After ?xed in formaldehyde solution, liver histomorphology was observed by hematoxylin-eosin (HE) staining under light microscope.The cholesterol crystallization was observed under light microscope. The expression of cholecystokinin (cholecystokinin,CCK), type B1 scavenger receptor (5RB1) in rat liver and Niemann Pick-C1-like protein-1 (NPC1L1) in small intestine was detected by enzyme-linked immunosorbent assay (ELISA). Results The model of hyperlipidemia was established successfully. Compared with the normal group, the model group showed significant steatosis in the liver, increased cholesterol concentration in bile, cholesterol stones or crystals visible to the naked eye, abnormal blood lipid levels, CCK, SRB1 and NPC1L1 expression in liver and small intestine. Compared with the model group, the levels of total cholesterol, total bile acid and blood lipid in bile in the middle and high dose groups of Shenling Baizhu powder decreased signi?cantly, the level of |
| Key words: Shenling Baizhu powder intestine-liveraxis CCK SRB1 NPC1L1 |
