复方丹参滴丸对糖尿病大鼠肾脏转化生长因子β1/Smads信号通路表达的影响  

Effect of compound Danshen dropping pills on the expression of TGF-beta 1/Smads signaling pathway in kidney of diabetic rats

作　　者：罗琼 李琴 石秀祯 郭爱莉 李静[2] LUO Qiong;LI Qin;SHI Xiuzhen;GUO Aili;LI Jing(Department of Endocrinology,Changjiang Shipping General Hospital,Wuhan,Hubei 430010,China;Department of Traditional Chinese Medicine,Union Medical College Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China)

机构地区：[1]长江航运总医院内分泌科,湖北武汉430010 [2]华中科技大学同济医学院附属协和医院中医科,湖北武汉430022

出　　处：《安徽医药》2021年第2期222-227,共6页Anhui Medical and Pharmaceutical Journal

摘　　要：目的观察复方丹参滴丸(DSP)对糖尿病大鼠肾脏组织转化生长因子β1(TGF-β1)/Smads信号通路表达的影响。方法链脲佐菌素诱导建立糖尿病大鼠模型,大鼠采用随机数字表法分为正常组(NC组)、糖尿病模型组(DM组)、复方丹参滴丸低剂量组(DSP低剂量组)、复方丹参滴丸高剂量组(DSP低剂量组)。DSP低、高剂量组大鼠每天分别给予200、400 mg/kg的DSP与生理盐水混悬液灌胃治疗,每日1次。8周末,检测各组大鼠空腹血糖、血肌酐、尿素氮表达水平;荧光定量PCR法检测各组大鼠肾脏组织TGF-β1、Smad2、Smad3、Smad7的mRNA表达水平;蛋白质印迹法(Western Blot)检测各组大鼠肾脏组织TGF-β1的蛋白表达;酶联免疫吸附(ELISA)法检测各组大鼠尿中肾损伤分子-1(KIM-1)、骨桥蛋白(OPN)以及肾脏组织pSmad2、p-Smad3、Smad7的浓度水平。结果与NC组相比,DM组大鼠空腹血糖[(27.19±1.55)mmol/L比(5.94±1.15)mmol/L]、血肌酐[(39.25±2.18)μmol/L比(26.20±1.18)μmol/L]、尿素氮[(12.81±0.65)mmol/L比(6.25±0.41)mmol/L]、尿KIM-1[(67.90±1.69)ng/L比(17.85±1.14)ng/L]、OPN浓度[(58.74±1.34)ng/L比(15.40±1.01)ng/L]明显升高(P<0.05);肾脏TGF-β1的mRNA[(1.72±0.15)比(1.00±0.00)]和蛋白表达[(0.81±0.05)比(0.27±0.06)]明显升高(P<0.05);肾脏Smad2[(1.80±0.09)比(1.00±0.00)]、Smad3的mRNA表达[(1.90±0.07)比(1.00±0.00)]以及p-Smad2[(69.45±1.43)ng/L比(10.71±1.09)ng/L]、p-Smad3的浓度[(65.73±1.79)ng/L比(9.84±0.33)ng/L]均明显升高(P<0.05),而肾脏Smad7的mRNA表达[(0.52±0.05)比(1.00±0.00)]和浓度[(10.61±0.65)ng/L比(21.02±1.32)ng/L]均明显降低(P<0.05)。与DM组相比,DSP低、高剂量组大鼠空腹血糖、血肌酐、尿素氮、尿KIM-1、尿OPN浓度明显降低(P<0.05),并抑制了肾脏TGF-β1/Smads信号通路的活性。结论DSP可能通过抑制DM大鼠肾脏TGF-β1/Smads信号通路,从而延缓DM大鼠肾脏损伤。Objective To observe the effect of compound Danshen dropping pills(DSP)on the expression of transforming growth factorβ1(TGF-β11)/Smads signaling pathway in kidney tissue of diabetic rats.MethodsDiabetic rats were induced by streptozotocin.The rats were randomly assigned into normal group(NC group),diabetic model group(DM group),low-dose group of compound Danshen dripping pills(DSP low-dose group)and high-dose group of compound Danshen dripping pills(DSP high-dose group).Rats in the lowand high-dose groups of DSP were given intragastric administration of the suspension of DSP and saline at 200 mg/kg and 400 mg/kg,respectively,once a day.At the end of 8 weeks,the expression levels of fasting blood glucose,creatinine and urea nitrogen in rats of each group were detected.The mRNA expression levels of TGF-β11,Smad2,Smad3 and Smad7 in kidney tissues of rats in each group were detected by fluorescence quantitative PCR.The protein expression of TGF-β11 in kidney tissues of rats in each group were detected by Western Blot.The concentrations of kidney injury molecule-1(KIM-1),osteopontin(OPN)in urine and p-Smad2,p-Smad3 and Smad7 in kidney tissues were measured by enzyme linked immunosorbent assay(ELISA).ResultsCompared with NC group,fasting blood glucose[(27.19±1.55)mmol/L vs.(5.94±1.15)mmol/L],serum creatinine[(39.25±2.18)μmol/L vs.(26.20±1.18)μmol/L],urea nitrogen[(12.81±0.65)mmol/L vs.(6.25±0.41)mmol/L],urinary KIM-1[(67.90±1.69)ng/L vs.(17.85±1.14)ng/L]and OPN levels[(58.74±1.34)ng/L vs.(15.40±1.01)ng/L]in DM group were significantly higher(P<0.05).The mRNA[(1.72±0.15)vs.(1.00±0.00)]and protein expressions[(0.81±0.05)vs.(0.27±0.06)]of TGF-β11 in kidney increased significantly(P<0.05).The mRNA expressions of Smad2[(1.80±0.09)vs.(1.00±0.00)]and Smad3[(1.90±0.07)vs.(1.00±0.00)]and the concentrations of p-Smad2[(69.45±1.43)ng/L vs.(10.71±1.09)ng/L]and p-Smad3[(65.73±1.79)ng/L vs.(9.84±0.33)ng/L]in kidney increased significantly(P<0.05),while the mRNA expressions[(0.52±0.05)vs.(1.00±0.00)]an

关 键 词：丹参 糖尿病肾病 复方丹参滴丸 肾脏 转化生长因子β1/Smads 大鼠 Wistar 

分 类 号：R285.5[医药卫生—中药学]