丹参酮ⅡA磺酸钠注射液改善脂多糖-高糖腹膜透析液诱导的人腹膜间皮细胞损伤的实验研究

SulfotanshinoneⅡA Sodium Ameliorates Lipopolysaccharide-Peritoneal Dialysis Solution-Elicited Human Peritoneal Mesothelial Cells Injury

目的评估丹参酮ⅡA磺酸钠注射液(STS)减轻脂多糖-高糖腹膜透析液(LPS-PDS)诱导的人腹膜间皮细胞(HPMCs)损伤以及抑制腹膜纤维化的作用。方法HPMCs来自腹腔外科手术患者腹膜细胞的原代培养。以LPS-PDS诱导的HPMCs损伤为模型,通过观察STS对HPMCs增殖活性、转化生长因子-β(TGF-β1)分泌、基质金属蛋白酶-9(MMP-9)、组织基质金属蛋白酶抑制因子-1(TIMP1)等的影响,阐明STS对HPMCs的保护作用及抗腹膜纤维化的机理。结果 LPS-PDS可造成HPMCs损伤,表现为活性下降,STS可明显减轻LPS-PDS对HPMCs的毒性,改善其造成的细胞活性下降,减轻LPSPDS诱导的TGF-β1、TIMP1mRNA上调和MMP-9mRNA表达下降。结论 STS可以减轻LPS-PDS诱导的HPMCs损伤,可能是通过调节TGF-β1、TIMP1、MMP-9等蛋白的表达,发挥保护腹膜细胞和拮抗腹膜纤维化的作用。

OBJECTIVE To study the effect and mechanism of sulfotanshinone ⅡA sodium(STS)in human peritoneal mesothelial cells(HPMCs)injury and peritoneal fibrosis caused by lipopolysaccharide-peritoneal dialysis solution(LPS-PDS).METHODS HPMCs was primary cultured from patients undergoing peritoneal surgery.The cells were incubated with LPSPDS to mimic the peritoneal dialysis conditions in vitro.After treatment of cells with STS,cellular viability was tested and mRNA were collected and subjected to RT-PCR to evaluated the level of TGF-β1,TIMP-1 and MMP-9.RESULTS Incubation HPMCs with LPS-PDS elicited cell injury.STS attenuated LPS-PDS-induced cell injury by improvement of cellular viability.Furthermore,STS inhibited HPMCs fibrosis as evidenced by suppression of TGF-β1 and TIMP1 induced by LPS-PDS and increasing MMP-9 mRNA level.CONCLUSION STS protects HPMCs against LPS-PDS-induced cell injury.Moreover,STS retards HPMCs fibrosis by decreasing TGF-β1 and TIMP1 mRNA level and increasing MMP-9 mRNA.