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芍药苷对2型糖尿病模型大鼠心肌损伤的改善作用及机制研究                                                                      Δ


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        李姗姗 ,田春雨        1,2,3 # ,张国伟 ,马雷雷 ,李继安 ,刘佳璇 ,刘 颖 ,李 爽 ,李小龙 ,沈佳欢(1.华北理工大
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        学药学院,河北 唐山 063210;2.华北理工大学中医学院,河北 唐山 063210;3.河北省中西医结合防治糖尿病
        及其并发症重点实验室,河北 唐山 063210)
        中图分类号 R285          文献标志码 A           文章编号 1001-0408(2021)23-2846-08
        DOI   10.6039/j.issn.1001-0408.2021.23.06
        摘   要   目的:研究芍药苷对2型糖尿病(T2DM)模型大鼠心肌损伤的改善作用及机制。方法:实验设置正常组、模型组、阳性对
        照组(二甲双胍 90 mg/kg)和芍药苷高、中、低剂量组(90、60、30 mg/kg),每组8只大鼠。除正常组外,其余各组大鼠均通过饲以高
        糖高脂饲料+腹腔注射链脲佐菌素(30 mg/kg)的方法建立T2DM模型。造模成功后,各给药组大鼠灌胃相应药液,正常组和模型
        组大鼠灌胃等体积生理盐水,每天1次,连续4周。测定大鼠体质量、空腹血糖值并进行口服葡萄糖耐量实验;测定大鼠血清中糖
        化血清蛋白(GSP)、总胆固醇(TC)、三酰甘油(TG)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肌
        酸激酶同工酶MB(CK-MB)、肌钙蛋白Ⅰ(cTnⅠ)水平,观察大鼠心肌组织病理形态学变化,检测大鼠心肌细胞凋亡指数,并分别
        采用免疫组化法和Western blot法检测大鼠心肌组织中B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、胱天蛋白酶3(caspase-3)
        蛋白表达水平。结果:与正常组比较,模型组大鼠体质量和血清中GSH-Px、SOD水平以及心肌组织中Bcl-2蛋白表达水平均显著
        降低(P<0.01),空腹血糖值、血糖曲线下面积、血清中生化指标(GSP、TC、TG、MDA、CK-MB、cTnⅠ)水平、心肌细胞凋亡指数和
        心肌组织中 Bax、caspase-3 蛋白表达水平均显著升高或增加(P<0.05 或 P<0.01);心肌组织排列相对不规则,部分肌纤维断裂。
        与模型组比较,除芍药苷低剂量组大鼠体质量和血清中SOD、MDA水平以及心肌组织中Bax蛋白表达水平外,芍药苷各剂量组大
        鼠的上述指标水平均得到显著回调(P<0.05或P<0.01)。结论:芍药苷可调节T2DM模型大鼠的糖脂代谢、增强其抗氧化能力、
        抑制其心肌细胞凋亡,对其心肌损伤具有一定的改善作用;该作用的分子机制可能与上调心肌组织中Bcl-2蛋白表达,下调心肌组
        织中Bax、caspase-3蛋白表达有关。
        关键词 芍药苷;2型糖尿病;心肌损伤;细胞凋亡

        Study on Improvement Effects and Mechanism of Paeoniflorin on Myocardial Injury in Type 2 Diabetic
        Model Rats
        LI Shanshan ,TIAN Chunyu 1,2,3 ,ZHANG Guowei ,MA Leilei ,LI Ji’an ,LIU Jiaxuan ,LIU Ying ,LI Shuang ,
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        LI Xiaolong ,SHEN Jiahuan(1. College of Pharmacy,North China University of Science and Technology,
                   2
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        Hebei Tangshan 063210,China;2. College of Traditional Chinese Medicine,North China University of Science
        and Technology,Hebei Tangshan 063210,China;3. Key Laboratory of Integrated Traditional Chinese and
        Western Medicine in Prevention and Treatment of Diabetes and Its Complications in Hebei Province,Hebei
        Tangshan 063210,China)
        ABSTRACT    OBJECTIVE:To study the improvement effects of paeoniflorin (PF) on myocardial injury in type 2 diabetes
        mellitus (T2DM) model rats and its mechanism. METHODS:The experiment was set up in the normal group,model group,
        positive control group(metformin 90 mg/kg),PF high-dose,medium-dose and low-dose groups(90,60,30 mg/kg),with 8 rats
        in each group. Except for normal group,other groups were given high-glucose and high-fat diet and intraperitoneal injection of
        streptozotocin (30 mg/kg) to induce T2DM model. After modeling, administration groups were given relevant medicine
        intragastrically,normal group and model group were given constant volume of normal saline intragastrically,once a day,for
        consecutive 4 weeks. The body weight,fasting blood glucose and oral glucose tolerance were measured;serum levels of
        glycosylated serum protein(GSP),total cholesterol(TC),triacylglycerol(TG),glutathione peroxidase(GSH-Px),superoxide
                                                            dismutase(SOD),malondialdehyde(MDA),creatine kinase
            Δ 基金项目:对发展中国家科技援助项目(No.KY201904005);河
                                                            isoenzyme-MB (CK-MB) and troponin Ⅰ (cTn Ⅰ) were
        北省自然科学基金资助项目(No.H2020209235);河北省中医药管理局
                                                            determined. The pathomorphological changes of myocardium
        科研计划项目(No.2020219);华北理工大学中医学院院内开放课题
        (No.ZY2021007);华北理工大学大学生创新创业训练计划项目(No.              were observed. The apoptosis index of rat cardiomyocytes was
                                                            detected. The protein expression of B-cell lymphoma 2
        X2019331)
            *硕士研究生。研究方向:药理学。E-mail:292312100@qq.com        (Bcl-2),Bcl-2 related X protein(Bax)and caspase-3 in rat
            # 通信作者:教授,硕士生导师,博士。研究方向:糖脂代谢性疾                  myocardium were detected by immunohistochemistry and
        病的中医药治疗。E-mail:tcy4479@sina.com                     Western blot. RESULTS:Compared with normal group,the


        ·2846 ·  China Pharmacy 2021 Vol. 32 No. 23                                 中国药房    2021年第32卷第23期
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