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·药学研究·

        环黄芪醇对四氯化碳致小鼠肝纤维化及糖酵解的影响                                                            Δ


        吴红雁 ,顾亚琴,周红成,陈 欣,张立虎(江苏医药职业学院医药生物技术研究院,江苏 盐城 224005)
              *
                                             #
        中图分类号 R965          文献标志码 A          文章编号 1001-0408(2022)14-1677-06
        DOI  10.6039/j.issn.1001-0408.2022.14.03
        摘  要   目的 研究环黄芪醇(CAG)对四氯化碳(CCl4 )诱导的小鼠肝纤维化(HF)及糖酵解的影响。方法 将雄性ICR小鼠随机分
        为空白组、模型组和CAG低、中、高剂量组(60、120、240 mg/kg),每组6只。除空白组小鼠腹腔注射橄榄油外,其余各组小鼠均腹
        腔注射 10%CCl4-橄榄油溶液(5 mL/kg),每周 3 次,持续 8 周以复制 HF 模型。自造模第 4 周起,各药物组小鼠灌胃相应药液(10
        mL/kg),空白组和模型组小鼠灌胃0.5%羧甲基纤维素钠溶液(10 mL/kg),每天1次,持续4周。实验过程中,称定小鼠的体质量;
        末次灌胃后,称定小鼠的肝脏质量并计算其肝脏指数,检测其肝损伤指标[天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)]、HF相关
        指标[苏木精-伊红(HE)染色评分、Masson 和天狼星红染色胶原容积分数、Ⅰ型胶原蛋白(collagen Ⅰ)、α-平滑肌肌动蛋白
       (α-SMA)]和糖酵解相关指标[乳酸(LD)、己糖激酶(HK)、磷酸果糖激酶(PFK)、丙酮酸激酶(PK)]的变化情况。结果 与模型组比
        较,各药物组小鼠胶原沉积和纤维化病变程度均有所减轻,体质量(CAG 低剂量组除外)均有所升高(P<0.05),肝脏指数,血清
        ALT、AST 水平,肝组织病理学 HE 染色评分、Masson 和天狼星红染色胶原容积分数,collagen Ⅰ、α-SMA 蛋白的表达水平,血清
        LD含量,以及血清、肝组织中HK、PFK、PK水平(CAG低剂量组肝组织除外)均显著降低(P<0.05)。结论 CAG对CCl4诱导的小
        鼠HF有改善作用,同时降低了其体内糖酵解关键酶和产物水平。
        关键词 环黄芪醇;肝损伤;肝纤维化;糖酵解;小鼠

        Effects of cycloastragenol on carbon tetrachloride-induced hepatic fibrosis and glycolysis in mice
        WU Hongyan,GU Yaqin,ZHOU Hongcheng,CHEN Xin,ZHANG Lihu(Institute of Biomedical Technology,
        Jiangsu Vocational College of Medicine,Jiangsu Yancheng 224005,China)

        ABSTRACT    OBJECTIVE To study the effects of cycloastragenol (CAG) on carbon tetrachloride (CCl4 )-induced hepatic
        fibrosis(HF)and glycolysis in mice. METHODS Male ICR mice were randomly divided into blank group,model group,CAG
        low-dose,medium-dose and high-dose groups(60,120,240 mg/kg),with 6 mice in each group. Except that blank group was
        given olive oil intraperitoneally,the mice in other groups were intraperitoneally injected with 10%CCl 4-olive oil solution(5 mL/kg)
        three times a week for 8 weeks to induce HF model. From the 4th week after modeling,mice in each drug group were given
        corresponding drug solution intragastrically (10 mL/kg),and mice in blank group and model group were given 0.5% sodium
        carboxymethyl cellulose solution intragastrically(10 mL/kg),once a day for 4 weeks. During the experiment,the body weight of
        mice were weighted;after last gastrogavage,the liver weight was weighted and liver indexes of mice were calculated. The changes
        of hepatic injury indexes [aspartate aminotransferase (AST) , alanine aminotransferase (ALT)], related indexes of
        HF [hematoxylin-eosin(HE)staining score,Masson and Picrosirius red staining collagen volume fraction,collagen Ⅰ,α-smooth
        muscle actin (α-SMA)] and related indexes of glycolysis [lactic acid (LD),hexokinase (HK),phosphofructokinase (PFK),
        pyruvate kinase(PK)] were all detected. RESULTS Compared with model group,the collagen deposition and fibrosis of mice in
        each drug group were reduced,and the body weights of mice(except for CAG low-dose group)were increased to some extent
       (P<0.05). Liver indexes,serum levels of ALT and AST,HE staining score of liver histopathology,Masson and Picrosirius red
        staining collagen volume fraction,protein expression of collagen Ⅰ and α-SMA,serum content of LD,the levels of HK,PFK
        and PK in serum and hepatic tissues(except for hepatic tissue of CAG low-dose group)were all decreased significantly(P<0.05).
        CONCLUSIONS CAG can improve HF in mice induced by CCl4,and reduce the levels of key enzymes and products of glycolysis.
        KEYWORDS    cycloastragenol;hepatic injury;hepatic fibrosis;glycolysis;mice

           Δ 基金项目 国家自然科学基金资助项目(No.81873134);江苏高
        校“青蓝工程”中青年学术带头人培养对象资助项目(No.苏教师函                        肝纤维化(hepatic fibrosis,HF)是由多种原因致慢
       〔2020〕10号);江苏高校“青蓝工程”优秀教学团队培养对象资助项目                 性肝损害所引发的病理改变,任何肝脏损伤在肝脏修复
       (No.苏教师函〔2021〕11号)
                                                           愈合的过程中都存在纤维化的过程;如果损伤因素长期
           *第一作者 副教授,博士。研究方向:中药药理学。电话:0515-
                                                           存在,纤维化的过程将长期持续,最终可能会发展为肝
        88159750。E-mail:why20133055@163.com
                                                                [1]
           # 通信作者 副教授,博士。研究方向:中药资源加工与利用。电                  硬化 。肝星状细胞(hepatic stellate cells,HSCs)主要位
        话:0515-88159280。E-mail:zlh800927@163.com           于肝脏的狄氏腔内,正常情况下处于静止状态;在外界

        中国药房2022年第33卷第14期                                                China Pharmacy 2022 Vol. 33 No. 14  ·1677 ·
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