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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。
Abstract：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-β and IL-6 in serum were detected by ELISA, the mRNA and protein levels of HMBG1, TGF-β and 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-β expression and content were significantly increased(P<0.05) in the RIRI+Danshensu Group, the change of TGF-β was 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.
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基本信息:
DOI：10.13417/j.gab.040.003318
中图分类号:R285.5
引用信息:
[1]李占鹰,贾林,石廷玉,等.丹参素对RIRI早期小鼠HMGB-1、IL-6和TGF-β的影响[J].基因组学与应用生物学,2021,40(Z3):3318-3323.DOI:10.13417/j.gab.040.003318.
基金信息:
国家自然科学基金项目(81760289); 国家自然科学青年基金项目(81801979); 湖北省风湿性疾病发生与干预重点实验室开放基金(OIR19008A)共同资助
2021-10-25
2021-10-25