复方丹参片对高脂血症模型大鼠血脂水平的改善及肾功能保护作用机制研究  

Study on the improvement of Compound danshen tablets on blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats

作　　者：张明昊[1] 高一盈 董文霞 王珍[1] 薛鹏坤 马伟洋 ZHANG Minghao;GAO Yiying;DONG Wenxia;WANG Zhen;XUE Pengkun;MA Weiyang(School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学医学院,郑州450046

出　　处：《中国药房》2022年第7期818-824,共7页China Pharmacy

基　　金：河南省重点研发与推广专项(科技攻关类)(No.212102311132)。

摘　　要：目的 探讨复方丹参片改善高脂血症大鼠血脂水平的作用及保护其肾功能的作用机制。方法 60只雄性SD大鼠分为正常组、模型组、辛伐他汀联合(2S)-N-[N-(3,5-二氟苯乙酰基)-L-丙氨酰]-2-苯基甘氨酸叔丁酯(DAPT)组和复方丹参片低、中、高剂量组,每组10只。正常组大鼠常规饲养;其余5组大鼠按10 m L/kg腹腔注射75%蛋黄乳液,禁食、自由饮水,16 h后饲喂高脂饲料,连续喂养4周造模。辛伐他汀联合DAPT组在造模同时灌胃辛伐他汀0.002 g/kg和DAPT 0.012 g/kg,复方丹参片低、中、高剂量组在造模同时分别灌胃复方丹参片0.25、0.5、1 g/kg,正常组、模型组灌胃等体积蒸馏水,每日1次,连续4周。采用生化法检测大鼠血清中总胆固醇(TC)、三酰甘油(TG)、肌酐(Cr)、尿素氮(BUN)水平;计算大鼠肾脏系数;采用苏木精-伊红染色法观察大鼠肾脏组织病理形态学变化,根据肾皮质区肾小管损伤和肾小球硬化程度进行肾损伤评分;采用免疫组化法检测肾脏组织中Notch信号受体1(Notch1)、Notch信号配体1(Jagged1)、发状分裂相关增强子1(Hes1)蛋白表达水平;采用实时荧光定量聚合酶链反应检测肾脏组织中Notch1、Jagged1、Hes1 m RNA表达水平。结果 与正常组比较,模型组大鼠血清中TG、TC、Cr、BUN水平均显著升高(P<0.05);肾脏系数显著升高(P<0.05);肾脏组织出现病理变化,肾小管损伤评分、肾小球硬化程度评分均显著升高(P<0.05);肾脏组织中Notch1、Jagged1、Hes1蛋白及m RNA表达水平均显著升高(P<0.05)。与模型组比较,复方丹参片低、中、高剂量组大鼠血清中TG、TC、Cr、BUN水平,肾脏系数,肾小管损伤评分,肾小球硬化程度评分,肾脏组织中Notch1、Jagged1、Hes1蛋白及mRNA表达水平均降低(P<0.05),且大部分指标呈现出剂量依赖趋势;肾脏组织病变程度减轻。结论 复方丹参片具有明显的降血脂作用,且可通过下调Notch1/Jagged1信号通路实现对高OBJECTIVE To investigate the effect of Compound danshen tablets on improving the blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats. METHODS Sixty male SD rats were divided into normal group, model group, simvastatin combined with(2S)-N-[N-(3,5-difluorophenylacetyl)-L-alanyl]-2-phenylglycine tert butyl(DAPT)group and low-dose,medium-dose and high-dose groups of Compound danshen tablets,with 10 rats in each group. Rats in the normal group received routine diet. The other 5 groups were intraperitoneally injected with 75% yolk emulsion 10 mL/kg,fasting and drinking freely. After 16 h,they were fed high-fat diet for 4 weeks. Simvastatin combined with DAPT group was given simvastatin 0.002 g/kg and DAPT 0.012 g/kg at the same time of modeling. The low-dose,medium-dose and high-dose groups of Compound danshen tablets were given Compound danshen tablets 0.25,0.5 and 1 g/kg respectively at the same time of modeling,the normal group and model group were given equal volume of distilled water,once a day,for 4 weeks. The serum levels of total cholesterol(TC),triglyceride(TG),creatinine(Cr)and urea nitrogen(BUN)in serum were detected by biochemical method;kidney coefficient of rats was calculated;histopathological changes of rat kidney were observed by HE staining,and the renal injury was scored according to the degree of renal tubular injury and glomerular sclerosis in renal cortex;expression levels of Notch signal receptor 1(Notch 1),Notch signal ligand 1(Jagged1)and hairy division associated enhancer 1(Hes1)in kidney were detected by immunohistochemistry;m RNA expressions of Notch1,Jagged1 and Hes1 in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Compared with normal group,the serum levels of TG,TC,Cr and BUN were increased significantly in model group(P<0.05);renal coefficient increased significantly(P<0.05);pathological changes occurred in renal tissue,and the scores of renal tubular injury and glomerular sclerosis increas

关 键 词：复方丹参片 高脂血症 肾功能 Notch信号受体1/Notch信号配体1信号通路 血脂 

分 类 号：R972[医药卫生—药品] R285.5[医药卫生—药学]