丹参素对RIRI早期小鼠HMGB-1、IL-6和TGF-β的影响

Effects of Danshensu on HMGB-1, IL-6 and TGF-β in Early Stage of Renal ischemia-reperfusion Injury in Mice

探讨丹参素对肾脏缺血再灌注损伤(renal ischemia-reperfusion injury,RIRI)早期小鼠高迁移率族蛋白1(high mobility group box protein 1,HMGB1)、白细胞介素6(interleukin-6,IL-6)和转化生长因子-β(transforming growth factor-β,TGF-β)的影响及其作用机制。采用背部双侧造模法制备RIRI模型小鼠。将小鼠随机分为5组:假手术(Sham)组、模型对照(RIRI)组、丹参素低、中、高剂量(RIRI+D-L/M/H)干预组,各组均在术后即刻、12 h两个时间点进行相关实验。应用全自动生化分析仪检测小鼠肾功能指标;HE染色镜检肾脏病理损伤程度;ELISA法检测血清中TGF-β、IL-6含量;分别应用RT-qPCR和Western Blot检测肾组织HMBG1、TGF-β和IL-6的mRNA和蛋白表达水平。结果表明,与RIRI组相比,Sham组、RIRI+D各组的肾脏损伤程度明显减轻,且血清中肌酐、尿素氮、HMGB1、IL-6表达及含量均显著降低(P<0.05),而TGF-β表达及含量显著升高(P<0.05);RIRI+D各组间除TGF-β变化与剂量呈正相关,其余各项指标均与剂量呈负相关。因此我们认为丹参素可能通过抑制HMGB1的释放,降低促炎因子IL-6、增加抑炎因子TGF-β的表达水平,从而对RIRI早期小鼠肾组织损伤产生保护作用。

To investigate the effects and mechanism of Danshensu on high mobility group box protein 1(HMGB1),interleukin-6(IL-6)and transforming growth factor-β(TGF-β)in early renal ischemia-reperfusion injury(RIRI)mice(Mus musculus).The RIRI model mice were prepared by the method of bilateral back modeling.The mice were randomly divided into 5 groups:sham group,model control(RIRI)group,RIRI+Danshensu(Low,Middle and High Dose)group.The indexes of renal function of mice were detected by automatic biochemical analyzer,the pathological degree of kidney was detected by HE staining,TGF-βand IL-6 in serum were detected by ELISA,the mRNA and protein levels of HMBG1,TGF-βand IL-6 were detected by RT-qPCR and Western Blot respectively.Compared with RIRI Group,the renal injury degree in sham group and RIRI+Danshensu groups was significantly lower than that in RIRI group,and the serum creatinine,urea nitrogen,HMGB1,IL-6expression and content were significantly decreased(P<0.05),while TGF-βexpression and content were significantly increased(P<0.05)in the RIRI+Danshensu Group,the change of TGF-βwas positively correlated with the dose,and the other indexes were negatively correlated with the dose.Therefore,Danshensu may inhibit the release of HMGB1,decrease the expression and synthesis of IL-6 and increase that of TGF-β,and protect the early RIRI mice from renal injury.