摘要
目的探讨肉苁蓉提取物松果菊苷(echinacoside,ECH)对糖尿病肾病(diabetic nephropathy,DN)大鼠肾功能紊乱、组织病理和系膜细胞损伤的保护作用及其机制。方法将60只SD大鼠随机分为对照组,模型组,松果菊苷高、中、低剂量(100、50、20 mg·kg^-1·d^-1)组和氯沙坦钾(16 mg·kg^-1·d^-1)组,每组10只。模型组、松果菊苷组和氯沙坦钾组饲喂高脂高糖饮食,腹腔注射链脲佐菌素(40 mg·kg^-1)建立糖尿病肾病大鼠模型。治疗2周后,记录大鼠的体质量、24 h饮水量和尿量;测定空腹血糖、血肌酐、尿素氮、尿微量蛋白、血清透明质酸(hyaluronic acid,HA)、组织金属蛋白酶抑制物-1(Tissue metalloproteinase inhibitor-1,TIMP-1)和层粘连蛋白(laminin,LN)含量;以HE染色和TUNEL染色观察肾脏组织病理变化;RT-PCR法检测B细胞淋巴瘤(B-cell lymphoma,Bcl-2)、Bcl-2相关X蛋白(Bcl2-associated X protein,Bax)、半胱天冬酶(Caspase-3)mRNA的表达;Western Blot法测定血管细胞黏附分子1(Vascular cell adhesion molecule-1, VCAM-1)、转化生长因子β(Transforming growth factor,TGF-β)和α平滑肌肌动蛋白(α-Smooth muscle actin,α-SMA)蛋白的表达。结果与对照组相比,模型组大鼠的体质量明显减少(P<0.05),饮水量、尿量、空腹血糖、尿微量白蛋白、尿素氮、肌酐、HA、TIMP-1和LN含量明显增加(P<0.05);Bax、Caspase-3 mRNA和VCAM-1、TGF-β、α-SMA蛋白的表达明显上调(P<0.05),Bcl-2 mRNA的表达明显下调(P<0.05)。与模型组相比,松果菊苷中、高剂量组和氯沙坦钾组大鼠的体质量明显增加(P<0.05),饮水量、尿量、空腹血糖、尿微量白蛋白、尿素氮、肌酐、HA、TIMP-1和LN含量明显减少(P<0.05);Bax、Caspase-3 mRNA和VCAM-1、TGF-β、α-SMA蛋白的表达明显下调(P<0.05),Bcl-2 mRNA的表达明显上调(P<0.05);HE和TUNEL染色显示肾组织病理变化明显减轻。结论中、高剂量的松果菊苷可能通过抑制TGF-β和VCAM-1蛋白的表达,抑制肾间质�
Objective To explore the protective effect of echinacoside(ECH) on renal dysfunction,histopathology and mesangial cell injury in diabetic nephropathy(DN) rats and its mechanism.Methods Sixty SD rats were randomly divided into control group,model group,ECH group(high,medium and low doses ECH,100,50,20 mg·kg^-1·d^-1) and losartan potassium group(losartan potassium,16 mg·kg^-1·d^-1),10 rats in each group.The model group,ECH group and losartan potassium group were fed with high-fat and high-sugar diet,and intraperitoneally injected streptozotocin(40 mg·kg^-1) to establish DN rat models.After 2 weeks of treatment,body weight,24 h water intake and urine volume of rats were recorded.The contents of fasting blood glucose,serum creatinine,urea nitrogen,urine microprotein,hyaluronic acid(HA),tissue metalloproteinase inhibitor-1(TIMP-1) and laminin(LN) were determined.HE staining and TUNEL staining were performed to observe pathological changes in kidney tissue.RT-PCR was performed to detect expression of B-cell lymphoma(Bcl-2),Bcl2-associated X protein(Bax),Caspase-3 mRNA.Western Blot was performed to determine expression levels of vascular cell adhesion molecule-1(VCAM-1),Transforming growth factor(TGF-β),α-Smooth muscle actin(α-SMA).Results Compared with control group,body weight of model group was significantly decreased(P<0.05),water intake,urine volume,fasting blood glucose,urine microalbumin,urea nitrogen,creatinine,HA,TIMP-1 and LN were significantly increased(P<0.05).Bax,Caspase-3 mRNA,and expression of VCAM-1,TGF-β and α-SMA protein were significantly up-regulated(P<0.05),expression of Bcl-2 mRNA was significantly down-regulated(P<0.05).Compared with model group,body weight of rats was significantly increased in medium-dose ECH group,high-dose ECH group and losartan potassium group(P<0.05),water intake,urine volume,fasting blood glucose,urine microalbumin,urea nitrogen,creatinine,HA,TIMP-1 and LN were significantly decreased(P<0.05).Bax,Caspase-3 mRNA,expression of VCAM-1,TGF-β and α-SMA protein were s
作者
何琴
刘帆
王鸿利
李剑萍
段俊
HE Qin;LIU Fan;WANG Hongli;LI Jianping;DUAN Jun(Department of Cadre Medicine,Caotang Ward,Sichuan People’s Hospital,Sichuan Academy of Medical Sciences,Chengdu 610072 Sichuan,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2020年第9期1029-1036,共8页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
四川省卫生和计划生育委员会科研项目(18PJ378)。
关键词
肉苁蓉
松果菊苷
糖尿病肾病
肾间质纤维化
凋亡
大鼠
Cistanches herba
Echinacoside
diabetic nephropathy
renal interstitial fibrosis
apoptosis
rats
