复方黄连胶囊对早期糖尿病肾病大鼠肾组织TGF—β1/BMP—7表达失衡及其Smad信号通路的调控作用(1)
[收稿日期] 2014-06-25
[基金项目] 安徽省科技计划项目(08020303074);安徽省卫生厅中医药科研课题(2012zy42)
[通信作者] 刘圣，主任中药师，教授，硕士生导师，Tel：(0551)62284029，E-mail：lslcclhl@163.com
[摘要] 目的：研究复方黄连胶囊(CRCC)对糖尿病肾病(DN)大鼠肾组织TGF-β1/BMP-7表达失衡及其Smad信号通路的调控作用，探讨CRCC对DN大鼠早期肾损伤的作用及其可能机制。方法：以链脲佐菌素(STZ)复制早期DN大鼠模型，动物分为正常组、模型组、消渴丸组(0.8 g·kg-1)、依那普利组(1 mg·kg-1)与CRCC 低、中、高剂量组(生药含量分别为1.09，2.18，4.36 g·kg-1)，灌胃给药，每天1次，5周后生化指标检测空腹血糖(FBG)、尿素氮(BUN)、血肌酐(Scr)、胰岛素(Ins)、24 h尿蛋白(24 h Upro)及24 h 尿微量白蛋白(24 h UmAlb);光镜观察肾组织形态学的改变;免疫组化法检测肾组织TGF-β1，BMP-7，Smad2/3，Smad1/5及Smad7蛋白表达;逆转录聚合酶链反应(RT-PCR)检测肾组织TGF-β1和BMP-7 mRNA表达。结果：与模型组比较，各CRCC治疗组均不同程度降低了DN大鼠FBG，BUN，Scr，24 h Upro 和24 h UmAlb水平，改善肾组织病理形态学异常，TGF-β1与Smad2/3蛋白表达减少，BMP-7，Smad1/5与Smad7蛋白表达增加，TGF-β1 mRNA表达减少，但BMP-7 mRNA表达未增加。结论：CRCC可改善早期DN大鼠肾功能病变，延缓DN慢性病理进展，其机制可能与通过Smad信号通路调控DN肾组织TGF-β1/BMP-7表达失衡有关。
, 百拇医药
[关键词] 复方黄连胶囊;糖尿病肾病;TGF-β1;BMP-7;Smad信号通路
Regulatory effect of compound Coptidis Rhizoma capsule on unbalanced
expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway
in rats with early diabetic nephropathy
LIU Sheng， CHEN Xiang-qing， TANG Li-qin， YU Na， ZHANG Xiao-li， DU Hong-fang
(1. Affiliated Provincial Hospital， Anhui Medical University， Hefei 230001， China;
, 百拇医药
2. Anhui University of Chinese Medicine， Hefei 230038， China)
[Abstract] Objective： To investigate the effect of compound Coptidis Rhizoma capsule(CCRC) on unbalanced expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway in rats with early diabetic nephropathy(DN)，and discuss CCRC′s effect on DN rats with early diabetic nephropathy and its possible mechanism. Method： DN model rats were established by injecting streptozotocin(STZ). The rats were randomly divided into seven groups： the normal group， the model group， the enalapril treatment group， the xiaoke pill treatment group and three CRCC treatment groups. They were orally administered once a day for five weeks. The fasting blood glucose(FBG)，blood urea nitrogen (BUN)，serum creatinine (Scr)， insulin(Ins)， 24 h urinary protein (24 h Upro) and 24 h urinary microalbumin (24 h UmAlb) were tested. The pathological changes in renal tissues were examined by optical microscopy. Immunohistochemical measures were used to detect the expressions of TGF-β1，BMP-7，Smad2/3，Smad1/5，and Smad7 protein，and RT-PCR was used to detect TGF-β1 mRNA and BMP-7 mRNA in renal tissues. Result： Compared with model group， BUN， Scr， Ins， 24 h Upro and 24 h UmAlb levels decreased at different degrees in CCRC treatment groups; the abnormal pathomorphology in renal tissue was improved; immunohistochemistry results showed that the expression of TGF-β1 and Smad2/3 were reduced， while the expression of BMP-7，Smad1/5 and Smad7 increased in CRCC treatment groups; the expression of TGF-β1 mRNA were reduced， but the expression of BMP-7 mRNA had no obvious change in CRCC treatment groups. Conclusion： CRCC can improve the early renal function， delay the progression of chronic renal pathology and maintain the dynamic balance of TGF-β1/BMP-7 expression in renal tissues of DN rats. The mechanism may be related to down-regulation of renal TGF-β1 and up-regulation of BMP-7 through Smad signaling pathway., 百拇医药(刘圣 陈象青 唐丽琴 余娜 张小力 杜红芳)
[基金项目] 安徽省科技计划项目(08020303074);安徽省卫生厅中医药科研课题(2012zy42)
[通信作者] 刘圣，主任中药师，教授，硕士生导师，Tel：(0551)62284029，E-mail：lslcclhl@163.com
[摘要] 目的：研究复方黄连胶囊(CRCC)对糖尿病肾病(DN)大鼠肾组织TGF-β1/BMP-7表达失衡及其Smad信号通路的调控作用，探讨CRCC对DN大鼠早期肾损伤的作用及其可能机制。方法：以链脲佐菌素(STZ)复制早期DN大鼠模型，动物分为正常组、模型组、消渴丸组(0.8 g·kg-1)、依那普利组(1 mg·kg-1)与CRCC 低、中、高剂量组(生药含量分别为1.09，2.18，4.36 g·kg-1)，灌胃给药，每天1次，5周后生化指标检测空腹血糖(FBG)、尿素氮(BUN)、血肌酐(Scr)、胰岛素(Ins)、24 h尿蛋白(24 h Upro)及24 h 尿微量白蛋白(24 h UmAlb);光镜观察肾组织形态学的改变;免疫组化法检测肾组织TGF-β1，BMP-7，Smad2/3，Smad1/5及Smad7蛋白表达;逆转录聚合酶链反应(RT-PCR)检测肾组织TGF-β1和BMP-7 mRNA表达。结果：与模型组比较，各CRCC治疗组均不同程度降低了DN大鼠FBG，BUN，Scr，24 h Upro 和24 h UmAlb水平，改善肾组织病理形态学异常，TGF-β1与Smad2/3蛋白表达减少，BMP-7，Smad1/5与Smad7蛋白表达增加，TGF-β1 mRNA表达减少，但BMP-7 mRNA表达未增加。结论：CRCC可改善早期DN大鼠肾功能病变，延缓DN慢性病理进展，其机制可能与通过Smad信号通路调控DN肾组织TGF-β1/BMP-7表达失衡有关。
, 百拇医药
[关键词] 复方黄连胶囊;糖尿病肾病;TGF-β1;BMP-7;Smad信号通路
Regulatory effect of compound Coptidis Rhizoma capsule on unbalanced
expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway
in rats with early diabetic nephropathy
LIU Sheng， CHEN Xiang-qing， TANG Li-qin， YU Na， ZHANG Xiao-li， DU Hong-fang
(1. Affiliated Provincial Hospital， Anhui Medical University， Hefei 230001， China;
, 百拇医药
2. Anhui University of Chinese Medicine， Hefei 230038， China)
[Abstract] Objective： To investigate the effect of compound Coptidis Rhizoma capsule(CCRC) on unbalanced expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway in rats with early diabetic nephropathy(DN)，and discuss CCRC′s effect on DN rats with early diabetic nephropathy and its possible mechanism. Method： DN model rats were established by injecting streptozotocin(STZ). The rats were randomly divided into seven groups： the normal group， the model group， the enalapril treatment group， the xiaoke pill treatment group and three CRCC treatment groups. They were orally administered once a day for five weeks. The fasting blood glucose(FBG)，blood urea nitrogen (BUN)，serum creatinine (Scr)， insulin(Ins)， 24 h urinary protein (24 h Upro) and 24 h urinary microalbumin (24 h UmAlb) were tested. The pathological changes in renal tissues were examined by optical microscopy. Immunohistochemical measures were used to detect the expressions of TGF-β1，BMP-7，Smad2/3，Smad1/5，and Smad7 protein，and RT-PCR was used to detect TGF-β1 mRNA and BMP-7 mRNA in renal tissues. Result： Compared with model group， BUN， Scr， Ins， 24 h Upro and 24 h UmAlb levels decreased at different degrees in CCRC treatment groups; the abnormal pathomorphology in renal tissue was improved; immunohistochemistry results showed that the expression of TGF-β1 and Smad2/3 were reduced， while the expression of BMP-7，Smad1/5 and Smad7 increased in CRCC treatment groups; the expression of TGF-β1 mRNA were reduced， but the expression of BMP-7 mRNA had no obvious change in CRCC treatment groups. Conclusion： CRCC can improve the early renal function， delay the progression of chronic renal pathology and maintain the dynamic balance of TGF-β1/BMP-7 expression in renal tissues of DN rats. The mechanism may be related to down-regulation of renal TGF-β1 and up-regulation of BMP-7 through Smad signaling pathway., 百拇医药(刘圣 陈象青 唐丽琴 余娜 张小力 杜红芳)