红景天总黄酮对大鼠心肌成纤维细胞增殖的抑制作用

Inhibitory effect of Rhodiola total flavonoids on proliferation of cardiac fibroblasts in rats

目的:研究红景天总黄酮对转化生长因子β1(TGF-β1)诱导的新生大鼠心肌成纤维细胞(CFB)增殖的抑制作用,探讨红景天总黄酮改善心肌纤维化的作用机制。方法:采用TGF-β1(5μg·L-1)诱导大鼠CFB增殖,构建心肌纤维化细胞模型。将正常培养的大鼠CFB分为对照组、模型组和25、50及100mg·L-1红景天总黄酮组。给药48h后,MTT法检测细胞活力,ELISA法检测细胞培养上清液中Ⅰ型胶原蛋白(ColⅠ)和Ⅲ型胶原蛋白(ColⅢ)的水平,检测上清液中总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSHPx)的活性以及丙二醛(MDA)、谷胱甘肽(GSH)的水平。结果:MTT法检测,与对照组比较,模型组细胞活力明显升高(P<0.01);与模型组,红景天总黄酮各剂量组细胞活力均明显下降(P<0.05)。T-SOD和MDA检测,与对照组比较,模型组细胞T-SOD活性下降(P<0.05),MDA水平明显升高(P<0.05);与模型组比较,50和100mg·L-1组细胞T-SOD活性明显升高(P<0.01),25和50 mg·L-1红景天总黄酮组MDA水平明显下降(P<0.05)。GSH-Px和GSH检测,与对照组比较,模型组细胞GSH-Px活性及GSH水平均明显降低(P<0.01);与模型组比较,红景天总黄酮各剂量组细胞GSH-Px活性和GSH水平均升高(P<0.05)。ColⅠ和ColⅢ水平测定,模型组ColⅠ和ColⅢ水平明显升高(P<0.01);与模型组比较,红景天总黄酮各剂量组细胞2种蛋白水平均明显下降(P<0.05)。结论:红景天总黄酮可以抑制大鼠CFB的增殖,并可能经抗氧化应激途径改善心肌纤维化。

Objective To investigate the inhibitory effect of Rhodiola total flavonoids on transforming growth factor （TGF）-β1-induced proliferation of cardiac fibroblasts （CFB） in the rats, and to explore its mechanisms of improving myocardial fibrosis.Methods 5 μg·L-1 TGF-β1 was used to induce the proliferation of CFB to build the cell models of myocardial fibrosis.The cultured CFB were divided into control group,model group,and low, medium,high doses （25,50 and 100 mg· L-1 ）of Rhodiola total flavonoids groups.The cells were treated for 48 h,the vitalities of cells were detected by MTT,the levels of collagen proteinⅠ （ColⅠ）and collagen proteinⅢ（Col Ⅲ）in supernatant were measured by ELISA,and the activities of total superoxide dismutase （T-SOD）and glutathione peroxidase （GSH-Px）were detected,the levels of malondialdehyde （MDA）and glutathione （GSH） were also measured.Results The MTT results indicated that compared with control group,the cell vitality in model group was significantly increased （P 〈 0.01 ）.compared with model group,the cell vitalities of CFB in Rhodiola total flavonoids groups were significantly decreased （P 〈 0.05 ）. Compared with control group, the T-SOD activity in model group was decreased, while the MDA level was significantly increased （P 〈0.05）;compared with model group,the T-SOD activities in 50 and 100 mg· L-1 Rhodiola total flavonoids groups were increased （P 〈0.01）;the MDA levels in 25 and 50 mg· L-1 groups were decreased significantly （P 〈 0.05）. Compared with control group,the GSH-Px activity and GSH level in model group were significantly decreased （P 〈0.01）.Compared with model group,the GSH-Px activities and GSH levels in Rhodiola total flavonoids groups were increased （P 〈0.05）.Compared with control group,the ColⅠand Col Ⅲ levels in model group were significantly increased （P 〈0.01）;compared with model group,the ColⅠand Col Ⅲ levels in Rhodiola total flavonoids groups were significantly decreased （P 〈0.05）.Conclusion Rhodiola total flavonoids can inhibit the proliferation of rat CFB.The development of myocardial fibrosis may be inhibited by Rhodiola total flavonoids through anti-oxidative stress pathway.