绞股蓝皂苷对AGEs诱导的人肾小球系膜细胞增殖及分泌细胞外基质的影响

Influence of gypenosides on the proliferation of HMCs and secretion of extracellular matrixc induced by AGEs

目的:观察绞股蓝皂苷(GP)对晚期糖基化终末产物(AGEs)诱导的人肾小球系膜细胞(HMCs)增殖及分泌细胞外基质(ECM)的影响。方法:将对数生长期的HMCs分为空白组、模型组、药物组、阳性组。空白组不给予任何诱导和干预,模型组、药物组、阳性组均采用200mg/L的AGEs诱导HMCs,药物组同时给予低、中、高剂量(25、75、150mg/L)的GP干预,阳性组同时给予0.1mmol/L的氨基胍盐酸盐(AG)干预,培养72h。采用MTT法观察各组中HMCs的增殖活性;Western blotting法检测核因子-κB(NF-κB)的表达;Real-Time PCR法检测转化生长因子-β1(TGF-β1)和血小板衍化生长因子-BB(PDGF-BB)m RNA的表达。结果:模型组中,AGEs能够诱导HMCs增殖、促进NF-κB活化及上调TGF-β1、PDGF-BB m RNA的表达,与空白组相比差异有统计学意义(P<0.01);药物组中,GP可以抑制AGEs诱导的HMCs增殖、NF-κB活化及下调TGF-β1、PDGF-BB m RNA的表达,与模型组相比差异有统计学意义(P<0.01)。结论:GP对AGEs培养条件下的HMCs具有一定的保护作用,GP可能通过抑制NF-κB活化及下调TGF-β1、PDGF-BB m RNA的表达,进而减少ECM的分泌和聚集,达到延缓糖尿病肾病进展的作用。

Objective： To observe the effect of Gypenosides（GP） on the proliferation of human mesangial cells（HMCs） and secretion of extracellular matrix（ECM） induced by AGEs. Methods： Logarithmic phase HMCs were divided into blank group, model group, drug group and positive group. Blank group was not given any induction and intervention; model group, drug group and positive group was induced by AGEs（200mg/L）; the drug group was intervened by low, medium and high dose（25,75,150mg/L） of GP at the same time, while positive group was given 0.1mmol/L aminoguanidine hydrochloride, all of which were cultured for 72 h. The inhibition of HMCs proliferation in each group was observed by MTT assay; the expression of nuclear factor κB（NF-κB） was detected by western blotting; the expression of TGF-β1 and PDGF-BB m RNA were detected by Semiquantitative RT-PCR. Results： in the model group, AGEs can induce HMCs proliferation, NF-κB activation and increase the expression of TGF-β1 and PDGF-BB m RNA, there was statistically significant compared with the control group（P〈0.01）; in the drug group, GP can inhibit the proliferation of HMCs induced by AGEs, inhibit NF-κB activation and down-regulates the expression of TGF-β1, PDGF-BB m RNA, there was statistically significant compared with the model（P〈0.01）. Conclusion： GP has a protective effect for HMCs cultured by AGEs, GP can inhibit the activation of NF-κB and down-regulates the expression of TGF-β1, PDGF-BB m RNA,thereby reducing the ECM secretion and aggregation to delay the progression of DN.