德都红花-7味散及其主要成分对肝纤维化小鼠CCR1、DNMT1蛋白的作用研究  

Effects of Deduhonghua-7 powder and its main components on CCR1 and DNMT1 proteins in mice with liver fibrosis

作　　者：巴图德力根[1] 韩志强[1] 韩格根套丽 徐艳华[1] 牧仁 安达[1] BA Tu-de-li-gen;HAN Zhi-qiang;HAN Ge-gen-tao-li;XU Yan-hua;MU Ren;AN Da(Institute of Clinical Pharmacology of Mongolian Medicine,Afiliated Hospital ofInnerMMongoliaMinzu University,Tongliao 028000,1Inner Mongolia Autonomous Region,China;School of Clinical Medicine,Affliated Hospital of Inner Mongolia Minzu University,Tongliao 028000,1Inner Mongolia Autonomous Region,China)

机构地区：[1]内蒙古民族大学附属医院蒙药临床药理研究所,内蒙古自治区通辽028000 [2]内蒙古民族大学临床医学院,内蒙古自治区通辽028000

出　　处：《中国临床药理学杂志》2024年第7期1004-1008,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81760908);国家十四五重点研发课题资助项目(2022YFC3502204)。

摘　　要：目的探索德都红花-7味散及其主要成分通过调控趋化因子受体(CCR1)DNA甲基转移酶1(DNMT1)抑制四氯化碳(CCl4)所致肝纤维化的影响。方法将C57BL/6小鼠随机分为空白组、模型组、德都红花-7味散组(灌胃0.75g·kg^(-1)德都红花-7味散)、蓝盆花组(灌胃0.75g·kg^(-1)蓝盆花)和木犀草素低、高剂量组(分别灌胃0.02、0.04g·kg^(-1)木犀草素)。除空白组外,其余各组均腹腔注射10%CCl4橄榄油溶液建立肝纤维化模型,各组均用0.5%CMC-Na溶解灌胃药物,每日1次,连续给药4周,末次给药后采集血液和肝组织。用酶联免疫吸附试验法检测血清DNMT1、CCR1、平滑肌肌动蛋白(α-smA)、Ⅲ型前胶原(precollagenⅢ)含量,用蛋白质印迹法检测DNMT1、CCR1、α-smA、Ⅰ型胶原(Collagen Ⅰ)蛋白表达情况。结果空白组、模型组、德都红花-7组、木犀草素低剂量组、木犀草素高剂量组、蓝盆花组血清DNMT1含量分别为(4.56±0.69)、(6.09±0.59)、(5.21±0.33)、(4.99±0.68)、(5.03±0.45)和(5.17±0.61)pg·mL^(-1)CCR1含量分别为(13.38±0.47)、(11.20±0.73)、(12.97±0.80)、(12.89±0.75)(12.88±0.95)和(12.92±0.58)pg·mL^(-1),α-smA含量分别为(181.80±24.50)、(281.30±26.60)、(220.90±22.30)(193.70±16.10)、(199.30±17.70)和(205.80±14.70)pg·mL^(-1),precollagenⅢ含量分别为(49.29±8.26)、(77.56±8.61)、(67.56±5.63)、(55.47±7.07)、(64.93±8.66)和(59.66±8.51)pg·mL^(-1),肝组织DNMT1蛋白相对表达水平分别为0.08±0.03、0.26±0.08、0.13±0.01、0.12±0.05、0.13±0.05和0.15±0.03,CCR1蛋白相对表达水平分别为0.18±0.03、0.13±0.02、0.21±0.06、0.22±0.07、0.17±0.07和0.18±0.06,α-smA蛋白相对表达水平分别为0.03±0.01、0.27±0.11、0.09±0.05、0.12±0.08、0.09±0.07和0.11±0.07,ColagenⅠ蛋白相对表达水平分别为0.09±0.04、0.65±0.22、0.28±0.12、0.26±0.19、0.30±0.22和0.25±0.12。模型组的上述指标与空白组比较,各给药组上述指标与模型组比较,在统计学上�Objective To elucidate the effect of Deduhonghua-7 powder and its main components on liver fibrosis induced by carbon tetrachloride(CCl4)by regulating chemokine receptor 1(CCR1)and DNA methyltransferase 1(DNMT1).Methods C57BL/6 mice were randomly divided into blank group,model group,Deduhonghua-7 powder group(0.75 g·kg^(-1)Deduhonghua-7 powder),Scabiosa Atropurea group(0.75 g·kg^(-1)Scabiosa Atropurea)and Luteolin-L,-H groups(0.02 and 0.04 g·kg^(-1)Luteolin,respectively).Except the blank group,the other groups were intrabitoneally injected with 10%CCl4 olive oil solution to establish liver fibrosis model,and all groups were given 0.5%CMC-Na dissolved intragastric drug once a day for 4 weeks,and blood and liver tissues were collected after the last administration.The serum CCR1,DNMT1,α-smooth muscle actin(α-smA)and precollagen II contents were detected by enzyme linked immunosorbent assay;the CCR1,DNMT1,α-smA,Collagen I protein expression were detected by Western blot.Result The contents of serum DNMT1 in blank group,model group,Deduhonghua-7 powder group,Luteotin-L,-H groups and Scabiosa Atropurea group were(4.56±0.69),(6.09±0.59),(5.21±0.33),(4.99±0.68),(5.03±0.45)and(5.17±0.61)pg·mL^(-1);the contents of CCR1were(13.38±0.47),(11.20±0.73),(12.97±0.80),(12.89±0.75)(12.88±0.95)and(12.92±0.58)pg·mL^(-1);the contents ofα-smA were(181.80±24.50),(281.30±26.60),(220.90±22.30),(193.70±16.10),(199.30±17.70)and(205.80±14.70)pg·mL^(-1);the contents of procollagen IⅡI were(49.29±8.26),(77.56±8.61),(67.56±5.63),(55.47±7.07),,(64.93±8.66)and(59.66±8.51)pg·mL^(-1);the relative expression levels of DNMT1 protein in liver tissues were 0.08±0.03,0.26±0.08,0.13±0.01,0.12±0.05,0.13±0.05 and 0.15±0.03;the CCR1 protein relative expression levels relative expression levels were 0.03±0.01,0.27±0.11,0.09±0.05,0.12±0.08,0.09±0.07 and 0.11±0.07;the expression of Colagen I protein were 0.09±0.04,0.65±0.22,0.28±0.12,0.26±0.19,0.30±0.22 and 0.25±0.12.The differences of above indicators be

关 键 词：德都红花-7味散 蓝盆花 木犀草素 肝纤维化 趋化因子受体 DNA甲基转移酶1 

分 类 号：R28[医药卫生—中药学]