文章摘要
罗琼,李琴,石秀祯,等.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[J].安徽医药,2021,25(2):222-227.
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
  
DOI:10.3969/j.issn.1009-6469.2021.02.003.
中文关键词: 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 )。
英文关键词: Salvia miltiorrhiza  Diabetic nephropathies  Compound Danshen dropping pills  Kidney  TGF-beta 1/Smads  Rats,Wistar
基金项目:
作者单位
罗琼 长江航运总医院内分泌科湖北武汉 430010 
李琴 长江航运总医院内分泌科湖北武汉 430010 
石秀祯 长江航运总医院内分泌科湖北武汉 430010 
郭爱莉 长江航运总医院内分泌科湖北武汉 430010 
李静 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 
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中文摘要:
      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)、复方丹参滴丸低法剂量组( 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。
英文摘要:
      Objective To observe the effect of compound Danshen dropping pills (DSP) on the expression of transforming growth factor β1 (TGF-β1 1)/Smads signaling pathway in kidney tissue of diabetic rats.Methods Diabetic 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 low-and 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 ofeach group were detected. The mRNA expression levels of TGF-β11,Smad2,Smad3 and Smad7 in kidney tissues of rats in each groupwere detected by fluorescence quantitative PCR. The protein expression of TGF-β1 1 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).Results Compared 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)] and concentrations [(10.61±0.65)ng/L vs. (21.02±1.32)ng/L] of Smad7 in kidney decreased significantly (P<0.05). Compared with DM group, the concentrations of fasting blood glucose, serum creatinine, urea nitrogen, urinary KIM-1 and urinary OPN in DSP low-and high-dose groups were significantly decreased (P < 0.05), and the activity of TGF-β11/Smads signaling pathway in kidney was inhibited.Conclusion DSP may delay renal injury in DM rats by inhibiting TGF-β11/Smads signaling pathway.
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