青藤碱对糖尿病大鼠肾脏TGF-β_1表达的影响

Effects of Sinomenine on Transforming Growth Factor-β_1 Expression in Diabetic Rat Kidney

目的研究青藤碱对糖尿病肾病(DN)大鼠肾脏转化生长因子β1(TGF-β1)表达的影响,以探讨青藤碱对DN大鼠的治疗作用及其机制。方法将健康雄性SD大鼠45只随机分为3组:正常对照组(N组)、DN组(D组)及青藤碱治疗组(S组),每组15只。S组在成模后皮下注射青藤碱20mg/(kg.d);D组给予等量生理盐水皮下注射,共给药6周。每2周观察大鼠体质量、血糖及24h尿蛋白排泄量的变化;每组每2周随机处死3只大鼠,取血标本测肌酐(Scr);取肾组织光镜观察病理改变,RT-PCR法检测肾组织中TGF-β1mRNA的表达。结果随着病程的延长,D组大鼠体质量增长慢、24h尿蛋白排泄量大、Scr水平高、TGF-β1mRNA表达水平高,与N组比较差异有显著性(P<0.05);S组大鼠体质量、24h尿蛋白排泄量及TGF-β1mRNA表达水平与D组比较明显改善,差异有显著性(P<0.05),Scr水平及光镜下病理改变有所好转,但差异无显著性意义(P>0.05)。大鼠肾组织TGF-β1mRNA表达水平与24h尿蛋白排泄量及Scr水平呈正相关(r=0.892,P<0.01;r=0.845,P<0.01)。结论青藤碱可通过下调肾组织TGF-β1的表达水平,对DN大鼠的肾脏起保护作用。

Objective To investigate the role of sinomenine on expression of renal transforming growth factorβ1 （TGF-β1） in diabetic nephropathy（DN）rats to further understand the therapeutic effect of sinomenine on DN rats. Methods Fourty five healthy male SD rats were randomly divided into three groups： normal control （Group N）, DN control （Group D） and sinomenine treated group（Group S） ,with fifteen rats in each group. The group S was treated with hypodermic injection of sinomenine [-20 mg/（kg ·d）-],and the group D was given the same dose of sodium chloride. The role of sinomenine was estimated by measuring the changes of body weight, serum glucose and 24 hour urinary protein excretion every two weeks. Meanwhile, three rats in each group were randomly killed and the inferior vena blood and renal tissue were collected for determination of serum creatinine, observation of renal pathological section and reverse transcription polymerase chain reaction （RT-PCR） analysis of TGF-β1 mRNA expression. Results Compared with group N, the body weight gain in group D was significantly lowered,and 24 hour urinary protein excretion, serum creatinine lever and TGF-β1 mRNA expression in group D were significantly increased （P〈0.05）. The body weight,24 hour urinary protein excretion and TGF-β1 mRNA expression in Group S were markedly improved compared with Group D（P〈0.05）. There was no significant difference in serum ereatinine level and pathologic changes between Group S and Group D（P〉0.05）. The renal TGF-β1 mRNA exhibited positive correlation with 24 hour urinary protein excretion and serum creatinine level（r=0.892,P〈0.01 ;r=0. 845,P〈0.01）. Conclusion Sinomenine exerted an early renal protective role on DN rats involving inhibition of TGF-β1 expression.